The Safety and Efficacy of Ramosetron versus Psyllium for the Treatment of Fecal Incontinence (SERAFI) : Study protocol for a randomized trial

The Safety and Efficacy of Ramosetron versus Psyllium for the Treatment of Fecal Incontinence (SERAFI) : Study protocol for a randomized trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Safety and Efficacy of Ramosetron versus Psyllium for the Treatment of Fecal Incontinence (SERAFI) : Study protocol for a randomized trial Jesung Park, Hong-Min Ahn, Seung-Bum Ryoo, Yungyeong Oh, Jin Sun Choi, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5153650/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 05 Nov, 2025 Read the published version in Trials → Version 1 posted 4 You are reading this latest preprint version Abstract Background : Fecal incontinence (FI) is a prevalent condition affecting 2% to 21% of the general population, with higher rates in older adults and specific settings such as nursing homes and hospitals. Current treatments include supportive care, biofeedback, anal injections, and sacral nerve stimulation, though these can be invasive or costly. Pharmacological therapies, like stool bulking agents and constipating agents, help manage symptoms but can have side effects. Ramosetron, a 5-HT3 receptor antagonist, shows promise for FI treatment by reducing intestinal motility and improving stool consistency. This study aims to compare the effectiveness and safety of Ramosetron (Irribow®) and AGIO granules (AGIO®) in treating FI. Methods : This study will include adults aged 19 and above diagnosed with FI. Participants will be randomly assigned to receive either Ramosetron (5μg for males, 2.5μg for females) or Psyllium (6g) once daily. The primary endpoint will compare changes in Fecal Incontinence Severity Index (FISI) scores before and after medication. Secondary endpoints will include comparisons of FISI scores, Fecal Incontinence Quality of Life (FIQL) scores, patient satisfaction surveys, and Bristol Stool Scale scores between the two groups. Follow-up visits will occur before treatment, and at 1, 4, and 12 months to assess symptoms and administer surveys. A sample size of 56 participants is needed for statistical significance at a 0.05 level with 0.8 power, accounting for dropout, totaling 148 participants. Discussion : It is believed that 5-HT3 receptor antagonists, along with Psyllium, can improve bowel habits and alleviate symptoms, thereby enhancing the quality of life for patients with FI. Trial registration : ClinicalTrials.gov NCT06166615, December 12, 2023 Fecal incontinence 5-HT3 receptor antagonist Ramosetron Psyllium Fecal Incontinence Severity Index Figures Figure 1 Administrative information Note: the numbers in curly brackets in this protocol refer to SPIRIT checklist item numbers. The order of the items has been modified to group similar items (see http://www.equator-network.org/reporting-guidelines/spirit-2013-statement-defining-standard-protocol-items-for-clinical-trials/). Title {1} The Safety and Efficacy of 5-HT3 Receptor antagonist (Ramosetron) versus Psyllium (Agio®) for the Treatment of Fecal Incontinence: Multicenter Randomized Trial (SERAFI) Trial registration {2a and 2b}. Our Study is registered at: ClinicalTrials.gov Under registration number: NCT06166615, December 12, 2023 URL : https://clinicaltrials.gov/study/NCT06166615 Protocol version {3} Ver. 1.6 Funding {4} National Cancer Center (323 Ilsan-ro, Ilsandong-gu, Goyang-si Gyeonggi-do, 10408, Republic of Korea) Author details {5a} 1) Seoul National University Hospital Jesung Park, MD. PhD. (First author) Seung-Bum Ryoo, MD., PhD. (First author) Yungyeong Oh 2) Boramae Medical Center Rumi Shin, MD., PhD. Jin sun Choi, MD. 3) Seoul National University Bundang Hospital Hong-Min Ahn, MD. (First author) Heung-Kwon Oh Name and contact information for the trial sponsor {5b} n/a Role of sponsor {5c} n/a Introduction Background and rationale {6a} Fecal incontinence (FI) is a significant and prevalent condition, with reported rates varying widely from 2% to 21% in the general population, and a median prevalence of 7.7% 1-3 4 . The prevalence of FI is influenced by age, showing lower rates in younger individuals and significantly higher rates among older adults. Additionally, FI is notably more common in specific settings, affecting 25% to 35% of nursing home residents and 10% to 25% of hospitalized patients 4-7 . These statistics underscore the considerable impact of FI across various demographics and highlight the importance of developing effective treatments to manage and alleviate this condition. Current treatments for fecal incontinence primarily consist of supportive care measures such as diet control, avoidance of aggravating factors 2 , and maintenance of anal skin hygiene 8 . Auxiliary treatments include biofeedback 9,10 , anal injections 11 , anal sphincteroplasty 12 , and sacral nerve stimulation 13 . These interventions aim to improve continence by enhancing anal sphincter and pelvic floor muscle function and addressing stool consistency and neurological functions. However, treatments like sacral nerve stimulation are often expensive or invasive, making them less accessible. Pharmacological therapies such as stool bulking agents (e.g., psyllium) and constipating agents (e.g., loperamide) are used to maintain stool consistency and reduce urgency 2,8,14,15 . Psyllium has been shown to be effective in improving FI symptoms in previous randomized controlled studies 15-17 . Psyllium and similar stool bulking agents help achieve pseudocontinence by increasing stool bulk and weight, promoting complete evacuation, and maintaining an empty rectum, thus preventing FI. Loperamide, while effective, can cause side effects such as constipation or toxic colitis, limiting its use 18,19 . 5-HT3 receptor antagonists, like Ramosetron (Irribow®), are being explored as an alternative treatment for FI. 5-Hydroxytryptamine (5-HT) is involved in regulating intestinal motility, mucus secretion, and bowel movements. 5-HT3 receptor antagonists reduce intestinal motility, harden stool texture, and decrease the frequency of urgent bowel movements 20 . Given the similarities between FI and IBS-D, where maintaining stool consistency is crucial for symptom control, Ramosetron is believed to be effective for FI 21-24 . Ramosetron has been shown to be safer and more effective than other drugs in its class. Although clinical trials for low anterior resection syndrome revealed that Ramosetron was effective in reducing stool frequencies, studies on the efficacy of Ramosetron in patients with FI are lacking 25 . This study aimed to compare the effectiveness and safety of treating FI with Ramosetron (Irribow®) and AGIO granules (AGIO®). We hypothesized that Ramosetron will be non-inferior to Psyllium in treating FI. Objectives {7} Treatment with a 5-HT3 receptor antagonist (Ramosetron (Irribow®)) or AGIO granules (AGIO®) can reduce the symptoms of fecal incontinence by maintaining stool consistency and reducing urgency, resulting in improvement of fecal incontinence severity score in the patient's quality of life. Primary hypothesis: Both Ramosetron (Irribow®) and Psyllium (AGIO®) will significantly reduce the severity of fecal incontinence, as measured by the Fecal Incontinence Severity Index (FISI) scores, in adult patients aged 19 and above diagnosed with fecal incontinence. Secondary hypothesis: Ramosetron (Irribow®) will be non-inferior to Psyllium (AGIO®) in reducing FISI scores. Patient satisfaction will differ between the Ramosetron and Psyllium groups. There will be a difference in stool consistency between the Ramosetron and Psyllium groups, as measured by the Bristol Stool Scale (BSS). Trial design {8} Multicenter, Randomized Parallel Single group Pre-Post Test, 1:1 allocation ratio, Pre-Post Comparison Clinical Trial Registration This study has been registered at the ClinicalTrials.gov database with the trial registration number NCT06166615. The full registry record can be accessed at https://clinicaltrials.gov/study/NCT06166615 Methods: Participants, interventions and outcomes Study setting {9} Seoul National University Hospital, Seoul, Republic of Korea Seoul National University Boramae Medical Center, Seoul, Republic of Korea Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea This study will be conducted at Seoul National University Hospital, Seoul National University Bundang Hospital, and Boramae Medical Center in Seoul, Republic of Korea. The study has been registered with ClinicalTrials.gov under the registry number NCT06166615. The project adheres to the ethical principles and national norms and standards approved by the respective Institutional Review Boards (IRBs) of Seoul National University Hospital, Seoul National University Bundang Hospital, and Boramae Medical Center. Eligibility criteria {10} 1) Inclusion criteria (1) Patients aged above 19 years old (2) Patients diagnosed with fecal incontinence (patients with fecal incontinence symptoms more than twice a month for at least 3 months) (3) Patients capable of compresence and follow the clinical trial (4) Patients willing to maintain contraception during the study period 2) Exclusion criteria (1) Patients unable to swallow oral medications (2) Patients with anatomical variance in colorectal surgery or pelvic surgery (3) Patients with Inflammatory bowel disease (4) Patients treating cancer related with gastrointestinal tract (5) Patients allergic to test drugs (6) Patients with overflow incontinence, fecal impaction on digital rectal examination (DRE) (7) Patients who took medication for fecal incontinence within 1 month before enrollment of the study (8) Pregnant and lactating female patients (9) Patients with contraindications to both test drugs (intestinal obstruction, intestinal stones, acute abdominal disease, undiagnosed abdominal pain/nausea/vomiting, gastrointestinal stenosis and dysphagia, megacolon syndrome, severe diabetes, etc.) (10) Patients taking two test drugs contraindicated in combination use (11) Patients who are judged by the principal investigator and research manager to be unsuitable for participation in clinical trials * When assessing the efficacy of medications for fecal incontinence, it is crucial to establish specific exclusion criteria to ensure the safety of participants and the integrity of the study results. Patients unable to swallow oral medications are excluded to ensure that all participants can properly ingest and absorb the medications being tested. Individuals with significant anatomical changes due to colorectal or pelvic surgery are excluded as they may have altered bowel function, which could confound the study results. Patients with inflammatory bowel disease are excluded due to the underlying gastrointestinal inflammation that could affect bowel habits independently of the medication being tested. Those treating cancer related to the gastrointestinal tract are also excluded, as cancer treatments can significantly impact bowel function, making it difficult to isolate the effects of the study medications. To ensure safety, anyone with known allergies to the study medications must be excluded to prevent adverse reactions. Individuals who took medication for fecal incontinence within one month before enrollment are excluded to prevent the influence of recent treatments on bowel function. Pregnant and lactating female patients are excluded to protect both mother and child, as the safety of the study medications for these groups has not been established. Patients with contraindications to both test drugs are excluded to prevent potential worsening of their conditions. Those taking two test drugs contraindicated in combination use are also excluded to avoid harmful drug interactions. Finally, patients deemed unsuitable for participation by the principal investigator and research manager are excluded to provide a safeguard, allowing clinical judgment to exclude any participant who may be at risk or unlikely to benefit from the study for unspecified reasons. By adhering to these exclusion criteria, the study aims to maintain a homogenous participant group, thereby enhancing the reliability and validity of the findings regarding the efficacy of the medications for treating fecal incontinence. 3) Surgeons with a subspecialty qualification in colorectal surgery Who will take informed consent? {26a} The researcher explains the study to patients who visit outpatient clinics with fecal incontinence Additional consent provisions for collection and use of participant data and biological specimens {26b} N/A Interventions Explanation for the choice of comparators {6b} 1) Irribow ® (Ramosetron HCl) A. Comparator: FISI scores before and after using Ramosetron. B. Reason: To evaluate the effectiveness of Ramosetron in improving fecal incontinence symptoms, we compare the pre-treatment and post-treatment states. 2) AGIO ® granules (Psyllium, (AGIO ® )) A. Comparator: FISI scores before and after using Psyllium. B. Reason: To evaluate the effectiveness of Psyllium in improving fecal incontinence symptoms, we compare the pre-treatment and post-treatment states. Intervention description {11a} Method in specific (1) Among patients diagnosed with fecal incontinence, select a group of patients who meet the inclusion and exclusion criteria. (2) Research consent from subject to the study is obtained and the subject will be divided into two test groups (Irribow® group, AGIO® group) through randomization. Random assignment will be carried out at MRCC through the researcher in charge, and the probability of a subject belonging to one group is equal. (3) The MRCC is the entity that prepares the allocation of unique codes (randomization table) for each group, and independently manages the preparation and allocation of the randomization table so that researchers remain blinded. If access to the code is unavoidably necessary due to an emergency situation such as a serious adverse drug reaction, or if it is deemed necessary for the rights and safety of the test subject, blinding can be lifted. When the blindness is lifted, only the unique code of the test subject can be viewed. Lifting the blindness should be considered on a case-by-case basis and only in serious medical emergencies. (4) The medication provided to the patient is packaged at the pharmacy at clinical trial center so that the researcher does not know which group the patient assigned. In this way, the researcher can evaluate the subject without any subjective evaluation. The blindness should be maintained by only the initials and assigned number of the patient are provided so that no one can know which group the subject belongs to. (5) The drug is administered once a day in the morning, regardless of meal, for 1 month. (6) On the visit ‘Before treatment’, ‘at 1 month’, ‘at 4 months’, and ‘at 12 months’ through an outpatient clinic, the Fecal Incontinence Severity Index (FISI), patient quality of life (QoL), patient satisfaction, and defecation pattern related to fecal incontinence symptoms (Bristol stool scale) were surveyed. If it is difficult to visit the outpatient clinic for one month, the questionnaire will be distributed in advance and instructed to fill out the information during the 4th cycle of medication and submit it at the clinic visit. (7) Compile the results of the questionnaire and analyze the correlation between them. Instructions of test drugs (1) Irribow ® (Ramosetron HCl) - Male: Orally administer 5㎍ once a day. The dose is appropriately increased or decreased depending on symptoms, and the minimum daily dose is 2.5㎍ and the maximum daily dose is 10㎍. - Women: Administer 2.5㎍ orally once a day. The dose is appropriately increased or decreased to 2.5㎍ depending on symptoms, and the maximum daily dose is 5㎍. * Regulatory authorities and clinical guidelines often recommend different dosages based on gender-specific data from clinical trials. For instance, the approved doses for Ramosetron in Japan and other countries typically recommend 5 μg for men and 2.5 μg for women for IBS-D, reflecting the findings from gender-specific analyses 23 . (2) AGIO ® granules (Psyllium, (AGIO ® )) - Administer 2 packets (12g) orally once a day. The dose is appropriately increased or decreased depending on symptoms, and the maximum daily dose is 18g (6g in the morning, 12g in the evening). Do not chew this medicine and take it with 1 to 2 cups of water. Criteria for discontinuing or modifying allocated interventions {11b} (1) When a permanent stoma was performed (2) Patient showing an allergy to the test drug (3) Inability to eat or defecate (4) Rectal bleeding of unknown cause occurs (5) Symptoms with severe dehydration (6) In case of acute abdominal disease or inflammatory bowel disease (7) In case of intestinal obstruction or intestinal stenosis (8) When another serious illness occurs and treatment is required (9) Where research cannot be performed properly (10) When the research subject withdraws participation Strategies to improve adherence to interventions {11c} Patients will receive detailed education and counseling on the importance of adherence to the prescribed medication regimen. This will include information on how the medication works, the expected benefits, and the importance of taking the medication as prescribed. Educational sessions will be provided at the start of the study and reinforced during follow-up visits. Follow-up visits will occur at 1 month, 4 months, and 12 months. During these visits, adherence will be monitored through patient interviews and medication logs. Each prescription will be provided in blister packs that clearly indicate the dosage schedule. Relevant concomitant care permitted or prohibited during the trial {11d} Other bulking agents, antidiarrheal drugs that inhibit intestinal motility (diphenoxylate, diphenoxin, loperamide hydrochloride, opium, etc.), and laxatives are prohibited from being used together while taking the test drug. Provisions for post-trial care {30} Patients will be scheduled for follow-up visits at post-trial to monitor their health status and manage any ongoing or new symptoms that may arise. if a side effect occurs due to the drug, the best treatment will be provided immediately, and the researcher will bear the appropriate treatment cost according to the registered clinical trial liability insurance. Participants will be informed about the results of the trial and its implications for their health. Outcomes {12} The primary outcome of this study is the change in the Fecal Incontinence Severity Index (FISI) from baseline (pre-treatment) to post-treatment in the two test groups. The mean change in FISI scores will be measured at baseline and 1-month post-treatment. This outcome measures the effectiveness of the interventions (Ramosetron and Psyllium) in reducing the severity of fecal incontinence, with a significant reduction indicating clinical efficacy. The secondary outcomes include the following: First, the difference in FISI scores between the two test groups. This will be measured by the mean difference in the change from baseline at 1 month, 4 months, and 12 months post-treatment, helping to determine which treatment is more effective. Second, the changes in quality of life (QoL) scores and patient satisfaction will be assessed using the Fecal Incontinence Quality of Life Scale (FIQL) and patient satisfaction surveys. The mean changes from baseline will be measured at the same time points, reflecting the broader impact of the treatments on patients' daily lives and overall well-being. Third, the differences in Bristol Stool Scale (BSS) scores will be evaluated by the mean change from baseline, also at the same time points, indicating the effect of the treatments on stool consistency. Additionally, clinical information such as age, gender, BMI, smoking status, past medical history, and survey dates will be collected to understand the demographic and clinical characteristics of the participants and to control for potential confounding factors in the analysis. Participant timeline {13} Sample size {14} The sample size was calculated using a method similar to the study by Markland et al. (2015) 15 . The Fecal Incontinence Severity Index (FISI) score decreased by 4.2 points, with a standard deviation of 11, in patients before and after treatment. With a significance level of 0.05 and a power of 0.8, 56 participants are needed. Accounting for a 20% dropout rate and an additional 10% dropout for those with less than 80% drug compliance, the final target is 74 subjects per group. Thus, a total of 148 patients will be required for the study. Recruitment {15} To recruit the research subjects, the researcher explains the study to patients who visit outpatient clinics with fecal incontinence and obtains consent for the participation. The principal investigator of the study and the clinical research team in each center will not exclude patients who may participate in this study based on race or socioeconomic status. If the patients meet the selection criteria for the study, researchers of the study will make every effort to allow as many patients as possible to participate in the study. The research subjects will be informed the purpose of the study so that they can represent the entire population of patients with fecal incontinence treated at our institution Assignment of interventions: allocation Sequence generation {16a} The allocation sequence for this clinical trial will be generated using SAS 9.4 software, which will create computer-generated random numbers. Stratification will be based on gender (men and women). The randomization will be conducted using a block randomization method to ensure a balanced allocation of participants to the two test groups (Ramosetron and Psyllium) in a 1:1 ratio. The randomization details, including the block size, will be documented separately and will not be accessible to the individuals responsible for enrolling participants or assigning interventions. Concealment mechanism {16b} The allocation sequence will be implemented through a web-based randomization system operated by the Medical Research Collaboration Center (MRCC) at Seoul National University College of Medicine/Seoul National University Hospital. This system will ensure that the sequence remains concealed until the interventions are assigned. The clinical trial center pharmacy will ship the medicines after confirming the randomization with MRCC. Clinical pharmacists, who are not part of the research team, will handle the medication distribution to maintain blinding. Implementation {16c} The allocation sequence will be generated by the MRCC at Seoul National University College of Medicine/Seoul National University Hospital. Participants will be enrolled by the clinical research coordinators, who will not have access to the allocation sequence. The assignment of participants to the interventions will be carried out through the web-based randomization system managed by MRCC. Assignment of interventions: Blinding Who will be blinded {17a} Blinding will be meticulously maintained for trial participants, care providers, outcome assessors, and data analysts. The Seoul National University Hospital Medical Research Collaborating Center (SNUH MRCC) will oversee the web-based randomization system, ensuring the blinding process is managed and maintained throughout the study. Participants will be randomly assigned to receive either Ramosetron (Irribow®) or Psyllium (AGIO®) using a computer-generated randomization sequence, which will be securely stored within the SNUH MRCC system, inaccessible to the research team. The system will conceal allocation using unique participant identifiers, ensuring that neither participants nor the research team can predict or influence group assignments. Clinical pharmacists, also blinded to the group assignments, will dispense medications based on codes provided by the web-based system, with medications labeled and packaged identically to maintain blinding for participants and care providers. Outcome assessors and data analysts will remain blinded to the allocation throughout data collection and analysis phases. The web-based system will securely manage and store all trial data, with restricted access to ensure blinding integrity. The SNUH MRCC will continuously monitor the system for potential breaches in blinding and conduct regular audits to ensure adherence to the blinding process throughout the study duration. By utilizing the SNUH MRCC's web-based randomization system, we ensure a robust and reliable blinding process, enhancing the validity and reliability of our study results. Procedure for unblinding if needed {17b} Unblinding will only be permissible in cases of medical emergencies where knowing the assigned intervention is essential for the participant’s safety. If unblinding is required, the principal investigator will make the decision and access the allocation information through the MRCC web-based system. The circumstances and reasons for unblinding will be documented and reported accordingly.. Data collection and management Plans for assessment and collection of outcomes {18a} The assessment and collection of outcome, baseline, and other trial data will be conducted through standardized procedures to ensure data quality and reliability. Outcome data, including FISI scores, FIQL scores, patient satisfaction surveys, and Bristol Stool Scale (BSS) scores, will be collected at baseline, 1 month, 4 months, and 12 months post-treatment. Baseline data such as age, gender, BMI, smoking status, past medical history, and survey dates will be recorded at the initial visit. Validated questionnaires, such as the FISI, FIQL, and BSS, will be used, with their reliability and validity well-documented in the literature. To enhance data quality, assessors will be trained to administer the questionnaires and collect data uniformly. Duplicate measurements will be taken where feasible to ensure accuracy, and regular data audits will be conducted to check for consistency and completeness. Data collection forms included in the protocol appendix will standardize data entry and ensure that all relevant information is collected systematically. Plans to promote participant retention and complete follow-up {18b} To promote participant retention and ensure complete follow-up in this study, several strategies will be implemented. Participants will receive reminders via text messages and phone calls prior to their scheduled follow-up visits to inform them of their appointment dates. Additionally, participants who complete all required surveys will be provided with a small incentive in the form of a gift card. These measures are designed to encourage continued participation and ensure that follow-up data is thoroughly collected. Data management {19} The data management plan for this study includes several key components to ensure the confidentiality, integrity, and security of the data. Data entry will be performed by trained personnel using a secure electronic database, with double data entry employed to minimize errors. Data will be coded using standardized coding schemes to ensure consistency and facilitate analysis. All electronic data will be encrypted and stored on secure servers with restricted access, while physical records will be stored in locked cabinets in a secure facility. Data will be retained for at least 3 years after the study ends, with provisions for extended storage for future research purposes, subject to participants' consent. Regular data inspection will be conducted to ensure data integrity and completeness. Confidentiality {27} The names of research subjects in the trial are initialized, and the subject identifier and medical record number are encrypted and managed by the principal investigator in each center in a separate file to prevent personal information from being exposed. Using the test results for purposes other than the original purpose of the study or providing them to others is limited to cases where the research subject gives written consent, and the inclusion of personal information in this case also depends on the subject's consent. If the research subject or legal representative requests to view or issue a copy of the records or consent form regarding test results and objections, the researcher will comply. In this clinical trial, files containing subjects' personal information and test results will be encrypted and stored so that only the principal investigator and researchers can view them. Samples will be managed and handled by assigning a research participation number that does not identify the individual. Research-related records are kept for 3 years from the end of the study period, and documents that are out of date of the storage institution are destroyed. However, there may be plans to keep it for more than 3 years for follow-up research, recording, and accumulation. Plans for collection, laboratory evaluation and storage of biological specimens for genetic or molecular analysis in this trial/future use {33} N/A Statistical methods Statistical methods for primary and secondary outcomes {20a} Effectiveness evaluation is conducted using the ITT (Intention-to-treat) analysis group as the main analysis and the PP (per-protocol) analysis group as the auxiliary analysis. The intent-to-treat (ITT) analysis group consists of subjects who are randomly assigned, administer the test drug at least once, and measure the primary endpoint (modified ITT). The per-protocol (PP) analysis group includes cases of failure to obtain consent, violation of selection/exclusion criteria, administration of prohibited drugs during the clinical trial period, and omission of major tests at the start and end of the clinical trial. A subject who completes the clinical trial protocol without violation and has drug compliance of 80% or more was also defined as PP analysis group. The safety evaluation analysis group includes subjects who have taken the test drug at least once. Reporting of results will mainly focus on data description, and for statistical analysis, Student t-test, Pearson χ2 test and Fisher's exact test will be used calculated by R version 4.4.0 (R Foundation for Statistical Computing, Vienna, Austria) (1) Primary endpoint: FISI (Fecal Incontinence Severity Index) at 1 month after administration (2) Secondary endpoints: QOL score, FISI (Fecal Incontinence Severity Index), and bowel movement pattern (Bristol stool scale) at 1, 4, and 12 months after administration. - Continuous variables present descriptive statistics (mean, standard deviation, median, minimum, maximum, etc.), and categorical variables present frequency and fraction. - At a significance level of 5%, continuous variables are tested using an independent t-test (two-tailed test), and categorical variables are tested using a Chi-square test (two-tailed test). If necessary, comparisons are made through non-parametric tests. - Safety evaluation: Safety evaluation will be based on side effects that occur during the study period. Frequency and fraction of side effects will be summarize and present with the 95% confidence intervals. Interim analyses {21b} An interim analysis of the primary endpoint will not be conducted, and no decision will be made to continue, change, or discontinue the trial. This decision is justified by several factors. First, no severe side effects of the drug have been reported, indicating a low risk profile that does not necessitate early stopping for safety concerns. Second, the minimum number of research subjects required to evaluate effectiveness has been judged to be 148 patients, ensuring that a sufficiently powered final analysis can be achieved only with the full cohort. Additionally, considering the trial duration and potential risks, conducting an interim analysis could introduce unnecessary complexity and potential biases, potentially compromising the integrity of the study. By foregoing interim analysis, we can maintain a straightforward and robust study design, ultimately providing more reliable and valid results. Methods for additional analyses (e.g. subgroup analyses) {20b} No specific subgroup analyses are planned. The primary and secondary outcomes will be analyzed for the entire study population without further stratification. If any unexpected trends or findings arise during the primary analysis, exploratory post-hoc analyses may be considered to investigate these observations, but these will be clearly identified as exploratory and not pre-specified. All analyses will be thoroughly documented, and the results will be interpreted with caution, taking into account the limitations of unplanned analyses. Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c} The primary analysis will be conducted on an intention-to-treat (ITT) basis, including all randomized participants regardless of protocol adherence. To address protocol non-adherence, a per-protocol (PP) analysis will also be performed, including only participants who adhered to the intervention protocols. Missing data will be handled using multiple imputation techniques to ensure robustness of the results. Specifically, multiple imputation will involve creating multiple datasets with imputed values based on an appropriate imputation model. Each dataset will be analyzed separately, and the results will be combined to provide estimates that account for the uncertainty due to missing data. This approach will enhance the reliability and validity of the study findings, ensuring comprehensive analysis despite missing values. Plans to give access to the full protocol, participant level-data and statistical code {31c} The results of the study will be disseminated through peer-reviewed journal articles and conference presentations. Access to the detailed data and protocol will be restricted to protect the confidentiality of the participants and the integrity of the research process. Researchers interested in further information or collaboration may contact the principal investigator, and requests will be considered on a case-by-case basis, in accordance with ethical guidelines and participants' consent. Oversight and monitoring Composition of the coordinating centre and trial steering committee {5d} The person in charge of monitoring is the lead principal investigator who regularly (once per year) confirms that the clinical trial protocol and GCP are being followed and reviews the supporting data to ensure that the recorded information are accurate. Make sure that the patient's handwritten questionnaire matches the case record. In addition, during the clinical trial, the evaluation results of the research subjects will be continuously monitored by the lead principal investigator. If an adverse reaction is reported, it will be immediately reported to the IRB, and the continuation of the clinical trial will be determined depending on the severity of the adverse reaction. Data analysis and writing of the results report for this study will also be carried out with the help of MRCC, which has no conflict of interest with this trial. Composition of the data monitoring committee, its role and reporting structure {21a} In this study, a separate Data Monitoring Committee (DMC) will not be established. Instead, the research team, in collaboration with the Medical Research Collaboration Center (MRCC) at Seoul National University College of Medicine/Seoul National University Hospital, will jointly monitor the trial. The monitoring team will consist of key members from the research team and representatives from the MRCC, including clinical experts, statisticians, and data management specialists. The joint monitoring team will oversee the safety and integrity of the trial, ensuring that all procedures adhere to the study protocol and regulatory requirements. They will regularly review interim data and safety reports to monitor the progress of the trial and ensure participant safety. The team will assess efficacy and safety data at predefined intervals and make decisions regarding the continuation, modification, or termination of the trial based on the data. Recommendations will be provided to the principal investigator regarding any necessary protocol modifications or other actions to ensure participant safety and data integrity. The monitoring team will report its findings and recommendations to the principal investigator after each review meeting. Regular meetings will be scheduled quarterly, with additional meetings held as needed in response to emerging safety concerns or other issues. This monitoring process ensures that significant findings are promptly communicated to the relevant parties to facilitate timely decision-making. Although an independent DMC is not established, efforts will be made to ensure that the monitoring process remains unbiased and objective. Members of the MRCC involved in monitoring will not have any financial or personal interests that could influence their judgment regarding the trial. Given the scope and potential risks of this clinical trial, the decision to use a joint monitoring approach involving the research team and MRCC is deemed sufficient to ensure effective oversight and the safety of all participants. This collaborative approach leverages the expertise of both groups to maintain rigorous monitoring standards throughout the trial. Adverse event reporting and harms {22} Side effects of the drug can be monitored through the usual history taking and physical examination during outpatient visits at 1 month (4 weeks after), 4 months, and 12 months after drug administration. Laboratory and radiological tests can be considered to check for complications and side effects of drugs. Additionally, if adverse reactions or side effects occur during drug administration, the research team will be discussing whether adjusting the outpatient treatment schedule or discontinuing the medication. If an adverse reaction or side effect occurs, documentation and report to the IRB is necessary. If it is a serious adverse event (SAE), it will be report immediately. Serious adverse reactions are defined as any unintended medical phenomenon that occurs in research subjects during a clinical trial, as follows: 1) When it causes death 2) Life-threatening: Life-threatening refers to a case where the investigator determines that the patient is at risk of death at the time of the incident, and does not include adverse reactions that could lead to death if the event becomes more serious. . 3) When hospitalization or extension of hospitalization period is necessary 4) If it causes persistent or significant disability or functional decline 5) Cases where congenital deformities or abnormalities occur in the offspring of research subjects (male or female) who received the clinical trial drug. 6) Reactions that endanger the study subject or require medical or surgical treatment to prevent the consequences listed above, even if they do not fall within the criteria listed above for seriousness. Frequency and plans for auditing trial conduct {23} The auditing of trial conduct will be performed internally by the research team across the three participating hospitals. Each hospital will be responsible for auditing the trial conduct at the other participating hospitals to ensure compliance with the study protocol, regulatory requirements, and Good Clinical Practice (GCP) guidelines. Audits will be conducted quarterly by each participating hospital. Each hospital will audit one of the other participating hospitals, rotating every quarter to ensure comprehensive coverage. The auditing process will involve a thorough review of trial documentation, including informed consent forms, case report forms, data entry logs, and any adverse event reports. Auditors will verify that the trial is being conducted in accordance with the approved protocol, GCP guidelines, and applicable regulatory requirements. After each audit, the auditing hospital will prepare a detailed report summarizing their findings, including any deviations from the protocol or areas of concern. This report will be shared with the audited hospital, the principal investigator, and the research team. The principal investigator at the audited hospital will be responsible for addressing any issues identified in the audit report and implementing corrective actions as necessary. Follow-up audits will be conducted to ensure that corrective actions have been properly implemented. By implementing this cross-hospital auditing system, the research team ensures continuous oversight and maintains high standards of trial conduct. This collaborative approach leverages the expertise of each participating hospital to enhance the integrity and quality of the study. Plans for communicating important protocol amendments to relevant parties (e.g. trial participants, ethical committees) {25} Any important protocol amendments, such as changes to eligibility criteria, outcomes, or analyses, will be communicated promptly to all relevant parties to ensure transparency and compliance with regulatory requirements. Protocol amendments will be immediately communicated to all investigators and research team members through email notifications and team meetings, with detailed documentation of the changes provided, along with a rationale for the amendments and any implications for the study conduct. For Institutional Review Boards (IRBs), protocol amendments will be submitted for review and approval. The submission will include a summary of the changes, the rationale for the amendments, and any updated study documents, such as informed consent forms and data collection forms. Approval from the IRBs will be obtained before implementing any changes. Participants will be informed of any protocol amendments that may affect their participation or the study outcomes through verbal and written notifications. These notifications will include a clear explanation of the changes, the reasons behind them, and any potential impact on their involvement in the study. Updated informed consent forms will be provided if necessary. Significant protocol amendments will be updated in the trial registries where the study is registered, such as ClinicalTrials.gov, including a summary of the changes and the date of the amendment. If the protocol amendments have implications for previously published protocols or ongoing submissions, the relevant journals will be notified, with a detailed explanation of the changes and their potential impact on the study findings provided. By following this comprehensive communication plan, the research team ensures that all relevant parties are promptly and adequately informed of important protocol amendments, maintaining transparency and regulatory compliance throughout the study. Dissemination plans {31a} The dissemination of trial results will be carried out through a comprehensive communication strategy aimed at ensuring that all relevant parties are informed of the findings. Participants will be informed of the trial results through personalized letters or emails, which will provide a summary of the study findings, the implications for their health, and any follow-up actions or recommendations. Healthcare professionals will be informed through presentations at medical conferences and meetings. Detailed findings will be published in peer-reviewed medical journals to ensure that clinicians and researchers have access to the data and can apply the findings in clinical practice. The trial results will be reported in relevant results databases, such as ClinicalTrials.gov, to ensure compliance with regulatory requirements and enhance transparency. Data sharing arrangements will be made with other researchers and institutions interested in conducting further analyses or secondary research, subject to data sharing agreements and ethical approvals. There will be no publication restrictions. The investigators will have the freedom to publish the trial results in a timely manner in accordance with the principles of academic freedom and scientific integrity. By following this dissemination plan, the research team ensure that trial results are effectively communicated to participants, healthcare professionals, the public, and other relevant groups, promoting transparency, knowledge sharing, and the application of research findings in practice. Discussion Currently, pharmacological treatments for fecal incontinence are limited to Psyllium and Loperamide. Many other treatments involve additional invasive procedures, highlighting the need for effective symptom management through simple oral medications 2 . Psyllium, being a granular formulation, poses difficulties for patients with swallowing disorders, while Loperamide carries the risk of severe constipation and toxic colitis 19 , 26 and has restrictions when used with cardiovascular medications 18 . Therefore, beyond demonstrating the superiority or non-inferiority of new drugs compared to existing ones, it is crucial to develop a broader range of pharmacological options for treating fecal incontinence. In general, comparative studies of pharmaceuticals typically involve evaluating the efficacy of two drugs against each other or comparing a drug's efficacy against a placebo. However, in this study, we aim to assess the performance of each drug using a pre-post comparison method and, as a secondary outcome, compare the two drugs. The rationale behind this approach is that demonstrating non-inferiority or superiority in the FISI change between the two drugs would require an excessively large initial sample size. Given that this is the first study on Ramosetron, we believe conducting a randomized parallel single-group pre-post test study as a preliminary research step is more prudent. This approach ensures patient safety and allows for a more efficient study design. Once the efficacy of Ramosetron is clearly demonstrated, we can then proceed to comparative studies with existing drugs. Using this method, we calculated that 74 patients per group, totaling 148 patients for both drug groups, would be necessary. This calculation aligns with the methodology used by Markland et al. in their 2015 study 15 . If this study confirms the efficacy and safety of Ramosetron, it will significantly expand the treatment options available to clinicians, allowing for more tailored and comprehensive management plans for patients. The potential impact on clinical guidelines would be substantial, as it would provide a new oral medication option that could be safer and more effective for certain populations. Specifically, Ramosetron could be particularly beneficial for patients who have difficulty swallowing granular medications like Psyllium or those who experience severe side effects from Loperamide. The confirmation of ramosetron’s efficacy and safety could lead to its inclusion in clinical guidelines for the treatment of fecal incontinence. This would provide an additional option for clinicians, enabling them to offer a medication that could be more suitable for patients with specific needs, such as those with cardiovascular comorbidities or those who are at risk for severe constipation and toxic colitis with Loperamide. If Ramosetron is shown to be effective, it could be recommended as a first-line or adjunctive treatment in managing fecal incontinence, particularly for patients who cannot tolerate current standard treatments. Based on the results of this study, future research could focus on direct comparative studies between Ramosetron and existing treatments such as Loperamide. Additionally, further studies could explore the specific efficacy of Ramosetron in subgroups of patients, such as those with predominantly loose stools or those with cardiovascular comorbidities where Loperamide use is restricted. This could help to refine treatment protocols and ensure that patients receive the most appropriate and effective care based on their individual conditions and risk profiles. In conclusion, this study represents a critical step in expanding the pharmacological toolkit for treating fecal incontinence. By establishing the efficacy and safety of Ramosetron, we pave the way for more nuanced and effective management strategies, ultimately improving patient outcomes and quality of life. Trial status Our trial protocol is currently at version 1.6, which was finalized on June 7, 2024. Recruitment for the trial began on January 19, 2024, and we anticipate that recruitment will be completed around June 2025. Abbreviations 5-HT3 receptor antagonist : 5-hydroxytryptamine 3 receptor antagonist BSS : Bristol stool scale FI : Fecal incontinence FISI : Fecal incontinence severity index FIQL : Fecal incontinence Quality of Life Declarations Acknowledgements Jesung Park, Hong-min Ahn and Seung-Bum Ryoo contributed equally as the first authors Rumi Shin are recognized as corresponding authors, having jointly overseen the research and contributed to the study's correspondence and coordination Correspondence to Rumi Shin, MD, PhD Associate Professor Division of Colorectal Surgery, Department of Sugery, Seoul National University Boramae Medical Center 20, Boramae-ro 5-gil, Dongjak-gu, Seoul, 07061, South Korea E-mail: [email protected] Supported by grant from the Seoul National University College of Medicine Research foundation Authors’ contributions {31b} Jesung Park, Hong-min Ahn and Seung-Bum Ryoo contributed equally as the first authors Rumi Shin are recognized as corresponding authors, having jointly overseen the research and contributed to the study's correspondence and coordination Jesung Park and Hong-min Ahn were responsible for the conceptualization and design of the study, as well as drafting the initial manuscript. Yungyeong Oh and Jin sun Choi conducted the data collection and management. Heung-Kwon Oh, Rumi Shin, and Seung-Bum Ryoo supervised the study and provided overall guidance. All authors read and approved the final manuscript. Funding {4} This research was supported by a grant of the Korean cancer survivors Healthcare R&D Project through the National Cancer Center, funded by the Ministry of Health & Welfare, Republic of Korea (RS-2023-CC140143) Availability of data and materials {29} The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. There are no contractual agreements that limit access to the data for any of the investigators involved in the study. Ethics approval and consent to participate {24} This study was approved by the Institutional Review Board (IRB) of Seoul National University Hospital, under the reference number 2303-158-1417. Written informed consent to participate in the study was obtained from all participants. For participants under the age of 18, consent was obtained from their parents or legal guardians. Consent for publication {32} Not applicable Competing interests {28} The authors declare that they have no competing interests Authors ’ information (optional) Jesung Park, MD. PhD. 1* , Hong-Min Ahn, MD. 4* , Seung-Bum Ryoo MD. PhD. 1,2* , Yungyeong Oh 1 , Jin Sun Choi, MD. 3 , Heung-Kwon Oh MD. PhD. 4 , Rumi Shin MD. PhD. 3 † 1. Department of Surgery, Seoul National University hospital, Seoul, Republic of Korea 2. Department of Surgery, Seoul National College of Medicine, Seoul, Republic of Korea 3. Department of Surgery, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea 4. Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Republic of Korea *Co-first author, †Corresponding author References Shah R, Villanueva Herrero JA. Fecal Incontinence. StatPearls . 2024. Menees S, Chey WD. Fecal Incontinence: Pathogenesis, Diagnosis, and Updated Treatment Strategies. Gastroenterol Clin North Am . Mar 2022;51(1):71-91. doi:10.1016/j.gtc.2021.10.005 Ng KS, Sivakumaran Y, Nassar N, Gladman MA. Fecal Incontinence: Community Prevalence and Associated Factors--A Systematic Review. Dis Colon Rectum . Dec 2015;58(12):1194-209. doi:10.1097/dcr.0000000000000514 Aitola P, Lehto K, Fonsell R, Huhtala H. Prevalence of faecal incontinence in adults aged 30 years or more in general population. Colorectal Dis . Jul 2010;12(7):687-91. doi:10.1111/j.1463-1318.2009.01878.x Pasricha T, Staller K. Fecal Incontinence in the Elderly. Clin Geriatr Med . Feb 2021;37(1):71-83. doi:10.1016/j.cger.2020.08.006 Rey E, Choung RS, Schleck CD, Zinsmeister AR, Locke GR, Talley NJ. Onset and risk factors for fecal incontinence in a US community. Am J Gastroenterol . Feb 2010;105(2):412-9. doi:10.1038/ajg.2009.594 Ditah I, Devaki P, Luma HN, et al. Prevalence, trends, and risk factors for fecal incontinence in United States adults, 2005-2010. Clin Gastroenterol Hepatol . Apr 2014;12(4):636-43.e1-2. doi:10.1016/j.cgh.2013.07.020 Omar MI, Alexander CE. Drug treatment for faecal incontinence in adults. Cochrane Database Syst Rev . Jun 11 2013;2013(6):CD002116. doi:10.1002/14651858.CD002116.pub2 Norton C, Chelvanayagam S, Wilson-Barnett J, Redfern S, Kamm MA. Randomized controlled trial of biofeedback for fecal incontinence. Gastroenterology . Nov 2003;125(5):1320-9. doi:10.1016/j.gastro.2003.09.039 Heymen S, Scarlett Y, Jones K, Ringel Y, Drossman D, Whitehead WE. Randomized controlled trial shows biofeedback to be superior to pelvic floor exercises for fecal incontinence. Dis Colon Rectum . Oct 2009;52(10):1730-7. doi:10.1007/DCR.0b013e3181b55455 Maeda Y, Laurberg S, Norton C. Perianal injectable bulking agents as treatment for faecal incontinence in adults. Cochrane Database Syst Rev . Feb 28 2013;(2):CD007959. doi:10.1002/14651858.CD007959.pub3 Bravo Gutierrez A, Madoff RD, Lowry AC, Parker SC, Buie WD, Baxter NN. Long-term results of anterior sphincteroplasty. Dis Colon Rectum . May 2004;47(5):727-31; discussion 731-2. doi:10.1007/s10350-003-0114-6 Wexner SD, Coller JA, Devroede G, et al. Sacral nerve stimulation for fecal incontinence: results of a 120-patient prospective multicenter study. Ann Surg . Mar 2010;251(3):441-9. doi:10.1097/SLA.0b013e3181cf8ed0 Jelovsek JE, Markland AD, Whitehead WE, et al. Controlling faecal incontinence in women by performing anal exercises with biofeedback or loperamide: a randomised clinical trial. Lancet Gastroenterol Hepatol . Sep 2019;4(9):698-710. doi:10.1016/s2468-1253(19)30193-1 Markland AD, Burgio KL, Whitehead WE, et al. Loperamide Versus Psyllium Fiber for Treatment of Fecal Incontinence: The Fecal Incontinence Prescription (Rx) Management (FIRM) Randomized Clinical Trial. Dis Colon Rectum . Oct 2015;58(10):983-93. doi:10.1097/dcr.0000000000000442 Bliss DZ, Jung HJ, Savik K, et al. Supplementation with dietary fiber improves fecal incontinence. Nurs Res . 2001;50(4):203-13. doi:10.1097/00006199-200107000-00004 Staller K, Song M, Grodstein F, et al. Increased Long-term Dietary Fiber Intake Is Associated With a Decreased Risk of Fecal Incontinence in Older Women. Gastroenterology . Sep 2018;155(3):661-667.e1. doi:10.1053/j.gastro.2018.05.021 Wu PE, Juurlink DN. Clinical Review: Loperamide Toxicity. Ann Emerg Med . Aug 2017;70(2):245-252. doi:10.1016/j.annemergmed.2017.04.008 McGregor A, Brown M, Thway K, Wright SG. Fulminant amoebic colitis following loperamide use. J Travel Med . 2007;14(1):61-2. doi:10.1111/j.1708-8305.2006.00096.x Scarlett Y. Medical management of fecal incontinence. Gastroenterology . Jan 2004;126(1 Suppl 1):S55-63. doi:10.1053/j.gastro.2003.10.007 Tomita T, Fukui H, Morishita D, et al. Efficacy of Serotonin Type 3 Receptor Antagonist Ramosetron on Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D)-Like Symptoms in Patients with Quiescent Inflammatory Bowel Disease: A Randomized, Double-Blind, Placebo-Controlled Trial. J Clin Med . Nov 22 2022;11(23)doi:10.3390/jcm11236882 Qi Q, Zhang Y, Chen F, Zuo X, Li Y. Ramosetron for the treatment of irritable bowel syndrome with diarrhea: a systematic review and meta-analysis of randomized controlled trials. BMC Gastroenterol . Jan 8 2018;18(1):5. doi:10.1186/s12876-017-0734-2 Fukudo S, Kinoshita Y, Okumura T, et al. Effect of ramosetron in female patients with irritable bowel syndrome with diarrhea: a phase III long-term study. J Gastroenterol . Sep 2016;51(9):874-82. doi:10.1007/s00535-016-1165-5 Min YW, Rhee PL. The clinical potential of ramosetron in the treatment of irritable bowel syndrome with diarrhea (IBS-D). Therap Adv Gastroenterol . May 2015;8(3):136-42. doi:10.1177/1756283X15572580 Ryoo SB, Park JW, Lee DW, et al. Anterior resection syndrome: a randomized clinical trial of a 5-HT3 receptor antagonist (ramosetron) in male patients with rectal cancer. Br J Surg . Jun 22 2021;108(6):644-651. doi:10.1093/bjs/znab071 Koo HL, Koo DC, Musher DM, DuPont HL. Antimotility agents for the treatment of Clostridium difficile diarrhea and colitis. Clin Infect Dis . Mar 01 2009;48(5):598-605. doi:10.1086/596711 Wald A, Bharucha AE, Limketkai B, et al. ACG Clinical Guidelines: Management of Benign Anorectal Disorders. Am J Gastroenterol . Oct 01 2021;116(10):1987-2008. doi:10.14309/ajg.0000000000001507 Cite Share Download PDF Status: Published Journal Publication published 05 Nov, 2025 Read the published version in Trials → Version 1 posted Reviewers agreed at journal 03 Aug, 2025 Reviewers invited by journal 09 May, 2025 Editor assigned by journal 11 Mar, 2025 First submitted to journal 11 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5153650","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":454304826,"identity":"e119f42b-e0e3-4a28-b8fe-929e284b940d","order_by":0,"name":"Jesung Park","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/ElEQVRIiWNgGAWjYDACCRjjAAPjgw8VQAYzcwPRWpgNZ5wBaWEkXgubNG8biEVAC//s5mOfK9vq5PiOH39sOHNebTR/O1DLj4ptuC25cyx55tm2w8aSZ3IMH3zcdjx3xmHGBsaeM7dxajGQyDFmbGw7kLjhQA6z4cxtx3IbgFqYGdvwacn/DNRSl7jh/PNn0rxzjuXOJ6wlhxmohTlxw40EM2nehprcDYS0SNxIM2ZsOAf0y403xoYzjh3I3QjUchCfX/hnJD9mbCgDhtj59IcPPtTU5c47f/jggx8VuLWAASMbnHkYTB7Arx4E/sBZdYQVj4JRMApGwYgDABjuYwM9u8xMAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0001-8740-0709","institution":"Seoul National University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Jesung","middleName":"","lastName":"Park","suffix":""},{"id":454304827,"identity":"6bb3b257-8c86-442c-9b25-1576eef86aea","order_by":1,"name":"Hong-Min Ahn","email":"","orcid":"","institution":"Seoul National University Bundang Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hong-Min","middleName":"","lastName":"Ahn","suffix":""},{"id":454304828,"identity":"9edef126-d741-4a16-a013-543142f13d10","order_by":2,"name":"Seung-Bum Ryoo","email":"","orcid":"https://orcid.org/0000-0001-6407-0444","institution":"Seoul National University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Seung-Bum","middleName":"","lastName":"Ryoo","suffix":""},{"id":454304829,"identity":"8d1fe593-c6f1-4aaf-8d18-ac1520c561b5","order_by":3,"name":"Yungyeong Oh","email":"","orcid":"","institution":"Seoul National University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yungyeong","middleName":"","lastName":"Oh","suffix":""},{"id":454304830,"identity":"91d084de-2781-4d33-85af-4f25834d30f8","order_by":4,"name":"Jin Sun Choi","email":"","orcid":"","institution":"Seoul National University Seoul Metropolitan Government Boramae Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Jin","middleName":"Sun","lastName":"Choi","suffix":""},{"id":454304831,"identity":"140a7ad9-21f1-4898-831b-45e20be3f991","order_by":5,"name":"Heung-Kwon Oh","email":"","orcid":"","institution":"Seoul National University Bundang Hospital","correspondingAuthor":false,"prefix":"","firstName":"Heung-Kwon","middleName":"","lastName":"Oh","suffix":""},{"id":454304832,"identity":"9d7e0e09-d5f4-4579-a202-111e1fb912d4","order_by":6,"name":"Rumi Shin","email":"","orcid":"https://orcid.org/0000-0001-5500-8702","institution":"Seoul National University Seoul Metropolitan Government Boramae Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Rumi","middleName":"","lastName":"Shin","suffix":""}],"badges":[],"createdAt":"2024-09-25 17:06:47","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5153650/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5153650/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13063-025-09165-2","type":"published","date":"2025-11-05T15:57:19+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82795673,"identity":"71903d8c-f6d5-4a1a-8a8e-9cf380bfa38c","added_by":"auto","created_at":"2025-05-15 10:36:04","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":32408,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSPIRIT Figure\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5153650/v1/5ce7a3e2a6101fc1cc1d961a.png"},{"id":95564226,"identity":"569911cd-dec5-4017-9575-fa605beaff76","added_by":"auto","created_at":"2025-11-10 16:09:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1621496,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5153650/v1/2c50236b-c8d7-45d9-bf99-7f3cc537e1b3.pdf"}],"financialInterests":"","formattedTitle":"The Safety and Efficacy of Ramosetron versus Psyllium for the Treatment of Fecal Incontinence (SERAFI) : Study protocol for a randomized trial","fulltext":[{"header":"Administrative information","content":"\u003cp\u003eNote: the numbers in curly brackets in this protocol refer to SPIRIT checklist item numbers. The order of the items has been modified to group similar items (see http://www.equator-network.org/reporting-guidelines/spirit-2013-statement-defining-standard-protocol-items-for-clinical-trials/).\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"639\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eTitle {1}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 421px;\"\u003e\n \u003cp\u003eThe Safety and Efficacy of 5-HT3 Receptor antagonist (Ramosetron) versus Psyllium (Agio\u0026reg;) for the Treatment of Fecal Incontinence: Multicenter Randomized Trial (SERAFI)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eTrial registration {2a and 2b}.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 421px;\"\u003e\n \u003cp\u003eOur Study is registered at: ClinicalTrials.gov\u003c/p\u003e\n \u003cp\u003eUnder registration number: NCT06166615, December 12, 2023\u003c/p\u003e\n \u003cp\u003eURL : https://clinicaltrials.gov/study/NCT06166615\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eProtocol version {3}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 421px;\"\u003e\n \u003cp\u003eVer. 1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eFunding {4}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 421px;\"\u003e\n \u003cp\u003eNational Cancer Center (323 Ilsan-ro, Ilsandong-gu, Goyang-si Gyeonggi-do, 10408, Republic of Korea)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eAuthor details {5a}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 421px;\"\u003e\n \u003cul\u003e\n \u003cli\u003e1) \u0026nbsp; \u0026nbsp; Seoul National University Hospital\u0026nbsp;\u003c/li\u003e\n \u003c/ul\u003e\n \u003cp\u003eJesung Park, MD. PhD. (First author)\u003c/p\u003e\n \u003cp\u003eSeung-Bum Ryoo, MD., PhD. (First author)\u003c/p\u003e\n \u003cp\u003eYungyeong Oh\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003e2) \u0026nbsp; \u0026nbsp; Boramae Medical Center\u003c/li\u003e\n \u003c/ul\u003e\n \u003cp\u003eRumi Shin, MD., PhD.\u003c/p\u003e\n \u003cp\u003eJin sun Choi, MD.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003e3) \u0026nbsp; \u0026nbsp; Seoul National University Bundang Hospital\u003c/li\u003e\n \u003c/ul\u003e\n \u003cp\u003eHong-Min Ahn, MD. (First author)\u003c/p\u003e\n \u003cp\u003eHeung-Kwon Oh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eName and contact information for the trial sponsor {5b}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 421px;\"\u003e\n \u003cp\u003en/a\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eRole of sponsor {5c}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 421px;\"\u003e\n \u003cp\u003en/a\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Introduction","content":"\u003cp\u003e\u003cstrong\u003eBackground and rationale {6a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFecal incontinence (FI) is a significant and prevalent condition, with reported rates varying widely from 2% to 21% in the general population, and a median prevalence of 7.7%\u003csup\u003e1-3\u003c/sup\u003e \u003csup\u003e4\u003c/sup\u003e. The prevalence of FI is influenced by age, showing lower rates in younger individuals and significantly higher rates among older adults. Additionally, FI is notably more common in specific settings, affecting 25% to 35% of nursing home residents and 10% to 25% of hospitalized patients\u003csup\u003e4-7\u003c/sup\u003e. These statistics underscore the considerable impact of FI across various demographics and highlight the importance of developing effective treatments to manage and alleviate this condition.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Current treatments for fecal incontinence primarily consist of supportive care measures such as diet control, avoidance of aggravating factors\u003csup\u003e2\u003c/sup\u003e, and maintenance of anal skin hygiene\u003csup\u003e8\u003c/sup\u003e. Auxiliary treatments include biofeedback\u003csup\u003e9,10\u003c/sup\u003e, anal injections\u003csup\u003e11\u003c/sup\u003e, anal sphincteroplasty\u003csup\u003e12\u003c/sup\u003e, and sacral nerve stimulation\u003csup\u003e13\u003c/sup\u003e. These interventions aim to improve continence by enhancing anal sphincter and pelvic floor muscle function and addressing stool consistency and neurological functions. However, treatments like sacral nerve stimulation are often expensive or invasive, making them less accessible.\u003c/p\u003e\n\u003cp\u003ePharmacological therapies such as stool bulking agents (e.g., psyllium) and constipating agents (e.g., loperamide) are used to maintain stool consistency and reduce urgency\u003csup\u003e2,8,14,15\u003c/sup\u003e. Psyllium has been shown to be effective in improving FI symptoms in previous randomized controlled studies\u003csup\u003e15-17\u003c/sup\u003e. Psyllium and similar stool bulking agents help achieve pseudocontinence by increasing stool bulk and weight, promoting complete evacuation, and maintaining an empty rectum, thus preventing FI. Loperamide, while effective, can cause side effects such as constipation or toxic colitis, limiting its use\u003csup\u003e18,19\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;5-HT3 receptor antagonists, like Ramosetron (Irribow\u0026reg;), are being explored as an alternative treatment for FI. 5-Hydroxytryptamine (5-HT) is involved in regulating intestinal motility, mucus secretion, and bowel movements. 5-HT3 receptor antagonists reduce intestinal motility, harden stool texture, and decrease the frequency of urgent bowel movements\u003csup\u003e20\u003c/sup\u003e. Given the similarities between FI and IBS-D, where maintaining stool consistency is crucial for symptom control, Ramosetron is believed to be effective for FI\u003csup\u003e21-24\u003c/sup\u003e.\u0026nbsp;Ramosetron has been shown to be safer and more effective than other drugs in its class.\u0026nbsp;Although clinical trials for low anterior resection syndrome revealed that Ramosetron was effective in reducing stool frequencies, studies on the efficacy of Ramosetron in patients with FI are lacking\u003csup\u003e25\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;This study aimed to compare the effectiveness and safety of treating FI with Ramosetron (Irribow\u0026reg;) and AGIO granules (AGIO\u0026reg;). We hypothesized that Ramosetron will be non-inferior to Psyllium in treating FI.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjectives {7}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTreatment with a 5-HT3 receptor antagonist (Ramosetron (Irribow\u0026reg;)) or AGIO granules (AGIO\u0026reg;) can reduce the symptoms of fecal incontinence by maintaining stool consistency and reducing urgency, resulting in improvement of fecal incontinence severity score in the patient\u0026apos;s quality of life.\u003c/p\u003e\n\u003cp\u003ePrimary hypothesis: Both Ramosetron (Irribow\u0026reg;) and Psyllium (AGIO\u0026reg;) will significantly reduce the severity of fecal incontinence, as measured by the Fecal Incontinence Severity Index (FISI) scores, in adult patients aged 19 and above diagnosed with fecal incontinence.\u003c/p\u003e\n\u003cp\u003eSecondary hypothesis: Ramosetron (Irribow\u0026reg;) will be non-inferior to Psyllium (AGIO\u0026reg;) in reducing FISI scores. Patient satisfaction will differ between the Ramosetron and Psyllium groups. There will be a difference in stool consistency between the Ramosetron and Psyllium groups, as measured by the Bristol Stool Scale (BSS).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial design {8}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMulticenter, Randomized Parallel Single group Pre-Post Test, 1:1 allocation ratio, Pre-Post Comparison\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial Registration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study has been registered at the ClinicalTrials.gov database with the trial registration number NCT06166615. The full registry record can be accessed at https://clinicaltrials.gov/study/NCT06166615\u003c/p\u003e"},{"header":"Methods: Participants, interventions and outcomes","content":"\u003cp\u003e\u003cstrong\u003eStudy setting {9}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSeoul National University Hospital, Seoul, Republic of Korea\u003c/p\u003e\n\u003cp\u003eSeoul National University Boramae Medical Center, Seoul, Republic of Korea\u003c/p\u003e\n\u003cp\u003eSeoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea\u003c/p\u003e\n\u003cp\u003eThis study will be conducted at Seoul National University Hospital, Seoul National University Bundang Hospital, and Boramae Medical Center in Seoul, Republic of Korea. The study has been registered with ClinicalTrials.gov under the registry number NCT06166615. The project adheres to the ethical principles and national norms and standards approved by the respective Institutional Review Boards (IRBs) of Seoul National University Hospital, Seoul National University Bundang Hospital, and Boramae Medical Center.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEligibility criteria {10}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1)\u0026nbsp; \u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eInclusion criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(1)\u0026nbsp;\u0026nbsp;Patients aged above 19 years old\u003c/p\u003e\n\u003cp\u003e(2)\u0026nbsp;\u0026nbsp;Patients diagnosed with fecal incontinence (patients with fecal incontinence symptoms more than twice a month for at least 3 months)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(3) \u0026nbsp;Patients capable of compresence and follow the clinical trial\u003c/p\u003e\n\u003cp\u003e(4) \u0026nbsp;Patients willing to maintain contraception during the study period\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2) \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eExclusion criteria\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(1) Patients unable to swallow oral medications\u003c/p\u003e\n\u003cp\u003e(2) Patients with anatomical variance in colorectal surgery or pelvic surgery\u003c/p\u003e\n\u003cp\u003e(3) Patients with Inflammatory bowel disease\u003c/p\u003e\n\u003cp\u003e(4) Patients treating cancer related with gastrointestinal tract\u003c/p\u003e\n\u003cp\u003e(5) Patients allergic to test drugs\u003c/p\u003e\n\u003cp\u003e(6) Patients with overflow incontinence, fecal impaction on digital rectal examination (DRE)\u003c/p\u003e\n\u003cp\u003e(7) Patients who took medication for fecal incontinence within 1 month before enrollment of the study\u003c/p\u003e\n\u003cp\u003e(8) Pregnant and lactating female patients\u003c/p\u003e\n\u003cp\u003e(9) Patients with contraindications to both test drugs (intestinal obstruction, intestinal stones, acute abdominal disease, undiagnosed abdominal pain/nausea/vomiting, gastrointestinal stenosis and dysphagia, megacolon syndrome, severe diabetes, etc.)\u003c/p\u003e\n\u003cp\u003e(10) Patients taking two test drugs contraindicated in combination use\u003c/p\u003e\n\u003cp\u003e(11) Patients who are judged by the principal investigator and research manager to be unsuitable for participation in clinical trials\u003c/p\u003e\n\u003cp\u003e* When assessing the efficacy of medications for fecal incontinence, it is crucial to establish specific exclusion criteria to ensure the safety of participants and the integrity of the study results. Patients unable to swallow oral medications are excluded to ensure that all participants can properly ingest and absorb the medications being tested. Individuals with significant anatomical changes due to colorectal or pelvic surgery are excluded as they may have altered bowel function, which could confound the study results. Patients with inflammatory bowel disease are excluded due to the underlying gastrointestinal inflammation that could affect bowel habits independently of the medication being tested. Those treating cancer related to the gastrointestinal tract are also excluded, as cancer treatments can significantly impact bowel function, making it difficult to isolate the effects of the study medications. To ensure safety, anyone with known allergies to the study medications must be excluded to prevent adverse reactions. Individuals who took medication for fecal incontinence within one month before enrollment are excluded to prevent the influence of recent treatments on bowel function. Pregnant and lactating female patients are excluded to protect both mother and child, as the safety of the study medications for these groups has not been established. Patients with contraindications to both test drugs are excluded to prevent potential worsening of their conditions. Those taking two test drugs contraindicated in combination use are also excluded to avoid harmful drug interactions. Finally, patients deemed unsuitable for participation by the principal investigator and research manager are excluded to provide a safeguard, allowing clinical judgment to exclude any participant who may be at risk or unlikely to benefit from the study for unspecified reasons. By adhering to these exclusion criteria, the study aims to maintain a homogenous participant group, thereby enhancing the reliability and validity of the findings regarding the efficacy of the medications for treating fecal incontinence.\u003c/p\u003e\n\u003cp\u003e3) \u003cstrong\u003eSurgeons\u003c/strong\u003e with a subspecialty qualification in colorectal surgery\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWho will take informed consent? {26a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe researcher explains the study to patients who visit outpatient clinics with fecal incontinence\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdditional consent provisions for collection and use of participant data and biological specimens {26b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eN/A\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInterventions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExplanation for the choice of comparators {6b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1)\u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eIrribow\u003csup\u003e\u0026reg;\u003c/sup\u003e (Ramosetron HCl)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA. \u0026nbsp; \u0026nbsp;Comparator: FISI scores before and after using Ramosetron.\u003c/p\u003e\n\u003cp\u003eB. \u0026nbsp; \u0026nbsp;Reason: To evaluate the effectiveness of Ramosetron in improving fecal incontinence symptoms, we compare the pre-treatment and post-treatment states.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2) \u0026nbsp; \u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAGIO\u003csup\u003e\u0026reg;\u003c/sup\u003e granules (Psyllium, (AGIO\u003csup\u003e\u0026reg;\u003c/sup\u003e))\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA. \u0026nbsp; \u0026nbsp;Comparator: FISI scores before and after using Psyllium.\u003c/p\u003e\n\u003cp\u003eB. \u0026nbsp; \u0026nbsp;Reason: To evaluate the effectiveness of Psyllium in improving fecal incontinence symptoms, we compare the pre-treatment and post-treatment states.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIntervention description {11a}\u003c/strong\u003e\u003cbr\u003e\u003cstrong\u003eMethod in specific\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(1) \u0026nbsp;Among patients diagnosed with fecal incontinence, select a group of patients who meet the inclusion and exclusion criteria.\u003c/p\u003e\n\u003cp\u003e(2)\u0026nbsp;\u0026nbsp;Research consent from subject to the study is obtained and the subject will be divided into two test groups (Irribow\u0026reg; group, AGIO\u0026reg; group) through randomization. Random assignment will be carried out at MRCC through the researcher in charge, and the probability of a subject belonging to one group is equal.\u003c/p\u003e\n\u003cp\u003e(3)\u0026nbsp;\u0026nbsp;The MRCC is the entity that prepares the allocation of unique codes (randomization table) for each group, and independently manages the preparation and allocation of the randomization table so that researchers remain blinded. If access to the code is unavoidably necessary due to an emergency situation such as a serious adverse drug reaction, or if it is deemed necessary for the rights and safety of the test subject, blinding can be lifted. When the blindness is lifted, only the unique code of the test subject can be viewed. Lifting the blindness should be considered on a case-by-case basis and only in serious medical emergencies.\u003c/p\u003e\n\u003cp\u003e(4)\u0026nbsp;\u0026nbsp;The medication provided to the patient is packaged at the pharmacy at clinical trial center so that the researcher does not know which group the patient assigned. In this way, the researcher can evaluate the subject without any subjective evaluation. The blindness should be maintained by only the initials and assigned number of the patient are provided so that no one can know which group the subject belongs to.\u003c/p\u003e\n\u003cp\u003e(5)\u0026nbsp;\u0026nbsp;The drug is administered once a day in the morning, regardless of meal, for 1 month.\u003c/p\u003e\n\u003cp\u003e(6) \u0026nbsp;On the visit \u0026lsquo;Before treatment\u0026rsquo;, \u0026lsquo;at 1 month\u0026rsquo;, \u0026lsquo;at 4 months\u0026rsquo;, and \u0026lsquo;at 12 months\u0026rsquo; through an outpatient clinic, the Fecal Incontinence Severity Index (FISI), patient quality of life (QoL), patient satisfaction, and defecation pattern related to fecal incontinence symptoms (Bristol stool scale) were surveyed. If it is difficult to visit the outpatient clinic for one month, the questionnaire will be distributed in advance and instructed to fill out the information during the 4th cycle of medication and submit it at the clinic visit.\u003c/p\u003e\n\u003cp\u003e(7) \u0026nbsp;Compile the results of the questionnaire and analyze the correlation between them.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInstructions of test drugs\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(1) Irribow\u003csup\u003e\u0026reg;\u003c/sup\u003e (Ramosetron HCl)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e- Male: Orally administer 5㎍\u0026nbsp;once a day.\u003c/p\u003e\n\u003cp\u003eThe dose is appropriately increased or decreased depending on symptoms, and the minimum daily dose is 2.5㎍ and the maximum daily dose is 10㎍.\u003c/p\u003e\n\u003cp\u003e- Women: Administer 2.5㎍\u0026nbsp;orally once a day.\u003c/p\u003e\n\u003cp\u003eThe dose is appropriately increased or decreased to 2.5㎍ depending on symptoms, and the maximum daily dose is 5㎍.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e* Regulatory authorities and clinical guidelines often recommend different dosages based on gender-specific data from clinical trials. For instance, the approved doses for Ramosetron in Japan and other countries typically recommend 5 \u0026mu;g for men and 2.5 \u0026mu;g for women for IBS-D, reflecting the findings from gender-specific analyses\u003csup\u003e23\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(2) AGIO\u003csup\u003e\u0026reg;\u003c/sup\u003e granules (Psyllium, (AGIO\u003csup\u003e\u0026reg;\u003c/sup\u003e))\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e- Administer 2 packets (12g) orally once a day.\u003c/p\u003e\n\u003cp\u003eThe dose is appropriately increased or decreased depending on symptoms, and the maximum daily dose is 18g (6g in the morning, 12g in the evening). Do not chew this medicine and take it with 1 to 2 cups of water.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCriteria for discontinuing or modifying allocated interventions {11b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(1)\u0026nbsp; \u0026nbsp;When a permanent stoma was performed\u003c/p\u003e\n\u003cp\u003e(2)\u0026nbsp; \u0026nbsp;Patient showing an allergy to the test drug\u003c/p\u003e\n\u003cp\u003e(3)\u0026nbsp; \u0026nbsp;Inability to eat or defecate\u003c/p\u003e\n\u003cp\u003e(4)\u0026nbsp; \u0026nbsp;Rectal bleeding of unknown cause occurs\u003c/p\u003e\n\u003cp\u003e(5)\u0026nbsp; \u0026nbsp;Symptoms with severe dehydration\u003c/p\u003e\n\u003cp\u003e(6)\u0026nbsp; \u0026nbsp;In case of acute abdominal disease or inflammatory bowel disease\u003c/p\u003e\n\u003cp\u003e(7)\u0026nbsp; \u0026nbsp;In case of intestinal obstruction or intestinal stenosis\u003c/p\u003e\n\u003cp\u003e(8)\u0026nbsp; \u0026nbsp;When another serious illness occurs and treatment is required\u003c/p\u003e\n\u003cp\u003e(9) \u0026nbsp; Where research cannot be performed properly\u003c/p\u003e\n\u003cp\u003e(10) \u0026nbsp;When the research subject withdraws participation\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStrategies to improve adherence to interventions {11c}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients will receive detailed education and counseling on the importance of adherence to the prescribed medication regimen. This will include information on how the medication works, the expected benefits, and the importance of taking the medication as prescribed. Educational sessions will be provided at the start of the study and reinforced during follow-up visits. Follow-up visits will occur at 1 month, 4 months, and 12 months. During these visits, adherence will be monitored through patient interviews and medication logs. Each prescription will be provided in blister packs that clearly indicate the dosage schedule.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRelevant concomitant care permitted or prohibited during the trial {11d}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOther bulking agents, antidiarrheal drugs that inhibit intestinal motility (diphenoxylate, diphenoxin, loperamide hydrochloride, opium, etc.), and laxatives are prohibited from being used together while taking the test drug. \u003cstrong\u003e\u003cbr\u003e\u0026nbsp;Provisions for post-trial care {30}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients will be scheduled for follow-up visits at post-trial to monitor their health status and manage any ongoing or new symptoms that may arise. if a side effect occurs due to the drug, the best treatment will be provided immediately, and the researcher will bear the appropriate treatment cost according to the registered clinical trial liability insurance. Participants will be informed about the results of the trial and its implications for their health.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcomes {12}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary outcome of this study is the change in the Fecal Incontinence Severity Index (FISI) from baseline (pre-treatment) to post-treatment in the two test groups. The mean change in FISI scores will be measured at baseline and 1-month post-treatment. This outcome measures the effectiveness of the interventions (Ramosetron and Psyllium) in reducing the severity of fecal incontinence, with a significant reduction indicating clinical efficacy.\u003c/p\u003e\n\u003cp\u003eThe secondary outcomes include the following: First, the difference in FISI scores between the two test groups. This will be measured by the mean difference in the change from baseline at 1 month, 4 months, and 12 months post-treatment, helping to determine which treatment is more effective. Second, the changes in quality of life (QoL) scores and patient satisfaction will be assessed using the Fecal Incontinence Quality of Life Scale (FIQL) and patient satisfaction surveys. The mean changes from baseline will be measured at the same time points, reflecting the broader impact of the treatments on patients\u0026apos; daily lives and overall well-being. Third, the differences in Bristol Stool Scale (BSS) scores will be evaluated by the mean change from baseline, also at the same time points, indicating the effect of the treatments on stool consistency.\u003c/p\u003e\n\u003cp\u003eAdditionally, clinical information such as age, gender, BMI, smoking status, past medical history, and survey dates will be collected to understand the demographic and clinical characteristics of the participants and to control for potential confounding factors in the analysis.\u003cbr\u003e\u003cstrong\u003eParticipant timeline {13}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSample size {14}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe sample size was calculated using a method similar to the study by Markland et al. (2015)\u003csup\u003e\u0026nbsp;15\u003c/sup\u003e. The Fecal Incontinence Severity Index (FISI) score decreased by 4.2 points, with a standard deviation of 11, in patients before and after treatment. With a significance level of 0.05 and a power of 0.8, 56 participants are needed. Accounting for a 20% dropout rate and an additional 10% dropout for those with less than 80% drug compliance, the final target is 74 subjects per group. Thus, a total of 148 patients will be required for the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRecruitment {15}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo recruit the research subjects, the researcher explains the study to patients who visit outpatient clinics with fecal incontinence and obtains consent for the participation. The principal investigator of the study and the clinical research team in each center will not exclude patients who may participate in this study based on race or socioeconomic status. If the patients meet the selection criteria for the study, researchers of the study will make every effort to allow as many patients as possible to participate in the study. The research subjects will be informed the purpose of the study so that they can represent the entire population of patients with fecal incontinence treated at our institution\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssignment of interventions: allocation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSequence generation {16a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe allocation sequence for this clinical trial will be generated using SAS 9.4 software, which will create computer-generated random numbers. Stratification will be based on gender (men and women). The randomization will be conducted using a block randomization method to ensure a balanced allocation of participants to the two test groups (Ramosetron and Psyllium) in a 1:1 ratio. The randomization details, including the block size, will be documented separately and will not be accessible to the individuals responsible for enrolling participants or assigning interventions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConcealment mechanism {16b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe allocation sequence will be implemented through a web-based randomization system operated by the Medical Research Collaboration Center (MRCC) at Seoul National University College of Medicine/Seoul National University Hospital. This system will ensure that the sequence remains concealed until the interventions are assigned. The clinical trial center pharmacy will ship the medicines after confirming the randomization with MRCC. Clinical pharmacists, who are not part of the research team, will handle the medication distribution to maintain blinding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eImplementation {16c}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe allocation sequence will be generated by the MRCC at Seoul National University College of Medicine/Seoul National University Hospital. Participants will be enrolled by the clinical research coordinators, who will not have access to the allocation sequence. The assignment of participants to the interventions will be carried out through the web-based randomization system managed by MRCC.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssignment of interventions: Blinding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWho will be blinded {17a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBlinding will be meticulously maintained for trial participants, care providers, outcome assessors, and data analysts. The Seoul National University Hospital Medical Research Collaborating Center (SNUH MRCC) will oversee the web-based randomization system, ensuring the blinding process is managed and maintained throughout the study. Participants will be randomly assigned to receive either Ramosetron (Irribow\u0026reg;) or Psyllium (AGIO\u0026reg;) using a computer-generated randomization sequence, which will be securely stored within the SNUH MRCC system, inaccessible to the research team. The system will conceal allocation using unique participant identifiers, ensuring that neither participants nor the research team can predict or influence group assignments. Clinical pharmacists, also blinded to the group assignments, will dispense medications based on codes provided by the web-based system, with medications labeled and packaged identically to maintain blinding for participants and care providers. Outcome assessors and data analysts will remain blinded to the allocation throughout data collection and analysis phases. The web-based system will securely manage and store all trial data, with restricted access to ensure blinding integrity. The SNUH MRCC will continuously monitor the system for potential breaches in blinding and conduct regular audits to ensure adherence to the blinding process throughout the study duration. By utilizing the SNUH MRCC\u0026apos;s web-based randomization system, we ensure a robust and reliable blinding process, enhancing the validity and reliability of our study results.\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;Procedure for unblinding if needed {17b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUnblinding will only be permissible in cases of medical emergencies where knowing the assigned intervention is essential for the participant\u0026rsquo;s safety. If unblinding is required, the principal investigator will make the decision and access the allocation information through the MRCC web-based system. The circumstances and reasons for unblinding will be documented and reported accordingly..\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData collection and management\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePlans for assessment and collection of outcomes {18a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe assessment and collection of outcome, baseline, and other trial data will be conducted through standardized procedures to ensure data quality and reliability. Outcome data, including FISI scores, FIQL scores, patient satisfaction surveys, and Bristol Stool Scale (BSS) scores, will be collected at baseline, 1 month, 4 months, and 12 months post-treatment. Baseline data such as age, gender, BMI, smoking status, past medical history, and survey dates will be recorded at the initial visit. Validated questionnaires, such as the FISI, FIQL, and BSS, will be used, with their reliability and validity well-documented in the literature.\u003c/p\u003e\n\u003cp\u003eTo enhance data quality, assessors will be trained to administer the questionnaires and collect data uniformly. Duplicate measurements will be taken where feasible to ensure accuracy, and regular data audits will be conducted to check for consistency and completeness. Data collection forms included in the protocol appendix will standardize data entry and ensure that all relevant information is collected systematically.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePlans to promote participant retention and complete follow-up {18b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo promote participant retention and ensure complete follow-up in this study, several strategies will be implemented. Participants will receive reminders via text messages and phone calls prior to their scheduled follow-up visits to inform them of their appointment dates. Additionally, participants who complete all required surveys will be provided with a small incentive in the form of a gift card. These measures are designed to encourage continued participation and ensure that follow-up data is thoroughly collected.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData management {19}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data management plan for this study includes several key components to ensure the confidentiality, integrity, and security of the data. Data entry will be performed by trained personnel using a secure electronic database, with double data entry employed to minimize errors. Data will be coded using standardized coding schemes to ensure consistency and facilitate analysis. All electronic data will be encrypted and stored on secure servers with restricted access, while physical records will be stored in locked cabinets in a secure facility. Data will be retained for at least 3 years after the study ends, with provisions for extended storage for future research purposes, subject to participants\u0026apos; consent. Regular data inspection will be conducted to ensure data integrity and completeness.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConfidentiality {27}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe names of research subjects in the trial are initialized, and the subject identifier and medical record number are encrypted and managed by the principal investigator in each center in a separate file to prevent personal information from being exposed. Using the test results for purposes other than the original purpose of the study or providing them to others is limited to cases where the research subject gives written consent, and the inclusion of personal information in this case also depends on the subject\u0026apos;s consent. If the research subject or legal representative requests to view or issue a copy of the records or consent form regarding test results and objections, the researcher will comply. In this clinical trial, files containing subjects\u0026apos; personal information and test results will be encrypted and stored so that only the principal investigator and researchers can view them. Samples will be managed and handled by assigning a research participation number that does not identify the individual. Research-related records are kept for 3 years from the end of the study period, and documents that are out of date of the storage institution are destroyed. However, there may be plans to keep it for more than 3 years for follow-up research, recording, and accumulation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePlans for collection, laboratory evaluation and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eN/A\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical methods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical methods for primary and secondary outcomes {20a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEffectiveness evaluation is conducted using the ITT (Intention-to-treat) analysis group as the main analysis and the PP (per-protocol) analysis group as the auxiliary analysis. The intent-to-treat (ITT) analysis group consists of subjects who are randomly assigned, administer the test drug at least once, and measure the primary endpoint (modified ITT). The per-protocol (PP) analysis group includes cases of failure to obtain consent, violation of selection/exclusion criteria, administration of prohibited drugs during the clinical trial period, and omission of major tests at the start and end of the clinical trial. A subject who completes the clinical trial protocol without violation and has drug compliance of 80% or more was also defined as PP analysis group. The safety evaluation analysis group includes subjects who have taken the test drug at least once.\u003c/p\u003e\n\u003cp\u003eReporting of results will mainly focus on data description, and for statistical analysis, Student t-test, Pearson \u0026chi;2 test and Fisher\u0026apos;s exact test will be used calculated by R version 4.4.0 (R Foundation for Statistical Computing, Vienna, Austria)\u003c/p\u003e\n\u003cp\u003e(1) \u0026nbsp; Primary endpoint: FISI (Fecal Incontinence Severity Index) at 1 month after administration\u003c/p\u003e\n\u003cp\u003e(2) \u0026nbsp; Secondary endpoints: QOL score, FISI (Fecal Incontinence Severity Index), and bowel movement pattern (Bristol stool scale) at 1, 4, and 12 months after administration.\u003c/p\u003e\n\u003cp\u003e- \u0026nbsp; \u0026nbsp; Continuous variables present descriptive statistics (mean, standard deviation, median, minimum, maximum, etc.), and categorical variables present frequency and fraction.\u003c/p\u003e\n\u003cp\u003e- \u0026nbsp; \u0026nbsp; At a significance level of 5%, continuous variables are tested using an independent t-test (two-tailed test), and categorical variables are tested using a Chi-square test (two-tailed test). If necessary, comparisons are made through non-parametric tests.\u003c/p\u003e\n\u003cp\u003e- \u0026nbsp; \u0026nbsp; Safety evaluation: Safety evaluation will be based on side effects that occur during the study period. Frequency and fraction of side effects will be summarize and present with the 95% confidence intervals.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInterim analyses {21b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAn interim analysis of the primary endpoint will not be conducted, and no decision will be made to continue, change, or discontinue the trial. This decision is justified by several factors. First, no severe side effects of the drug have been reported, indicating a low risk profile that does not necessitate early stopping for safety concerns. Second, the minimum number of research subjects required to evaluate effectiveness has been judged to be 148 patients, ensuring that a sufficiently powered final analysis can be achieved only with the full cohort. Additionally, considering the trial duration and potential risks, conducting an interim analysis could introduce unnecessary complexity and potential biases, potentially compromising the integrity of the study. By foregoing interim analysis, we can maintain a straightforward and robust study design, ultimately providing more reliable and valid results.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods for additional analyses (e.g. subgroup analyses) {20b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo specific subgroup analyses are planned. The primary and secondary outcomes will be analyzed for the entire study population without further stratification. If any unexpected trends or findings arise during the primary analysis, exploratory post-hoc analyses may be considered to investigate these observations, but these will be clearly identified as exploratory and not pre-specified. All analyses will be thoroughly documented, and the results will be interpreted with caution, taking into account the limitations of unplanned analyses.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary analysis will be conducted on an intention-to-treat (ITT) basis, including all randomized participants regardless of protocol adherence. To address protocol non-adherence, a per-protocol (PP) analysis will also be performed, including only participants who adhered to the intervention protocols. Missing data will be handled using multiple imputation techniques to ensure robustness of the results. Specifically, multiple imputation will involve creating multiple datasets with imputed values based on an appropriate imputation model. Each dataset will be analyzed separately, and the results will be combined to provide estimates that account for the uncertainty due to missing data. This approach will enhance the reliability and validity of the study findings, ensuring comprehensive analysis despite missing values.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePlans to give access to the full protocol, participant level-data and statistical code {31c}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe results of the study will be disseminated through peer-reviewed journal articles and conference presentations. Access to the detailed data and protocol will be restricted to protect the confidentiality of the participants and the integrity of the research process. Researchers interested in further information or collaboration may contact the principal investigator, and requests will be considered on a case-by-case basis, in accordance with ethical guidelines and participants\u0026apos; consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOversight and monitoring\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eComposition of the coordinating centre and trial steering committee {5d}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe person in charge of monitoring is the lead principal investigator who regularly (once per year) confirms that the clinical trial protocol and GCP are being followed and reviews the supporting data to ensure that the recorded information are accurate. Make sure that the patient\u0026apos;s handwritten questionnaire matches the case record. In addition, during the clinical trial, the evaluation results of the research subjects will be continuously monitored by the lead principal investigator. If an adverse reaction is reported, it will be immediately reported to the IRB, and the continuation of the clinical trial will be determined depending on the severity of the adverse reaction. Data analysis and writing of the results report for this study will also be carried out with the help of MRCC, which has no conflict of interest with this trial.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eComposition of the data monitoring committee, its role and reporting structure {21a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this study, a separate Data Monitoring Committee (DMC) will not be established. Instead, the research team, in collaboration with the Medical Research Collaboration Center (MRCC) at Seoul National University College of Medicine/Seoul National University Hospital, will jointly monitor the trial. The monitoring team will consist of key members from the research team and representatives from the MRCC, including clinical experts, statisticians, and data management specialists.\u003c/p\u003e\n\u003cp\u003eThe joint monitoring team will oversee the safety and integrity of the trial, ensuring that all procedures adhere to the study protocol and regulatory requirements. They will regularly review interim data and safety reports to monitor the progress of the trial and ensure participant safety. The team will assess efficacy and safety data at predefined intervals and make decisions regarding the continuation, modification, or termination of the trial based on the data. Recommendations will be provided to the principal investigator regarding any necessary protocol modifications or other actions to ensure participant safety and data integrity.\u003c/p\u003e\n\u003cp\u003eThe monitoring team will report its findings and recommendations to the principal investigator after each review meeting. Regular meetings will be scheduled quarterly, with additional meetings held as needed in response to emerging safety concerns or other issues. This monitoring process ensures that significant findings are promptly communicated to the relevant parties to facilitate timely decision-making.\u003c/p\u003e\n\u003cp\u003eAlthough an independent DMC is not established, efforts will be made to ensure that the monitoring process remains unbiased and objective. Members of the MRCC involved in monitoring will not have any financial or personal interests that could influence their judgment regarding the trial. Given the scope and potential risks of this clinical trial, the decision to use a joint monitoring approach involving the research team and MRCC is deemed sufficient to ensure effective oversight and the safety of all participants. This collaborative approach leverages the expertise of both groups to maintain rigorous monitoring standards throughout the trial.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdverse event reporting and harms {22}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSide effects of the drug can be monitored through the usual history taking and physical examination during outpatient visits at 1 month (4 weeks after), 4 months, and 12 months after drug administration. Laboratory and radiological tests can be considered to check for complications and side effects of drugs. Additionally, if adverse reactions or side effects occur during drug administration, the research team will be discussing whether adjusting the outpatient treatment schedule or discontinuing the medication.\u003c/p\u003e\n\u003cp\u003eIf an adverse reaction or side effect occurs, documentation and report to the IRB is necessary. If it is a serious adverse event (SAE), it will be report immediately. Serious adverse reactions are defined as any unintended medical phenomenon that occurs in research subjects during a clinical trial, as follows:\u003c/p\u003e\n\u003cp\u003e1) When it causes death\u003c/p\u003e\n\u003cp\u003e2) Life-threatening: Life-threatening refers to a case where the investigator determines that the patient is at risk of death at the time of the incident, and does not include adverse reactions that could lead to death if the event becomes more serious. .\u003c/p\u003e\n\u003cp\u003e3) When hospitalization or extension of hospitalization period is necessary\u003c/p\u003e\n\u003cp\u003e4) If it causes persistent or significant disability or functional decline\u003c/p\u003e\n\u003cp\u003e5) Cases where congenital deformities or abnormalities occur in the offspring of research subjects (male or female) who received the clinical trial drug.\u003c/p\u003e\n\u003cp\u003e6) Reactions that endanger the study subject or require medical or surgical treatment to prevent the consequences listed above, even if they do not fall within the criteria listed above for seriousness.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFrequency and plans for auditing trial conduct {23}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe auditing of trial conduct will be performed internally by the research team across the three participating hospitals. Each hospital will be responsible for auditing the trial conduct at the other participating hospitals to ensure compliance with the study protocol, regulatory requirements, and Good Clinical Practice (GCP) guidelines.\u003c/p\u003e\n\u003cp\u003eAudits will be conducted quarterly by each participating hospital. Each hospital will audit one of the other participating hospitals, rotating every quarter to ensure comprehensive coverage. The auditing process will involve a thorough review of trial documentation, including informed consent forms, case report forms, data entry logs, and any adverse event reports. Auditors will verify that the trial is being conducted in accordance with the approved protocol, GCP guidelines, and applicable regulatory requirements.\u003c/p\u003e\n\u003cp\u003eAfter each audit, the auditing hospital will prepare a detailed report summarizing their findings, including any deviations from the protocol or areas of concern. This report will be shared with the audited hospital, the principal investigator, and the research team. The principal investigator at the audited hospital will be responsible for addressing any issues identified in the audit report and implementing corrective actions as necessary. Follow-up audits will be conducted to ensure that corrective actions have been properly implemented.\u003c/p\u003e\n\u003cp\u003eBy implementing this cross-hospital auditing system, the research team ensures continuous oversight and maintains high standards of trial conduct. This collaborative approach leverages the expertise of each participating hospital to enhance the integrity and quality of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePlans for communicating important protocol amendments to relevant parties (e.g. trial participants, ethical committees) {25}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAny important protocol amendments, such as changes to eligibility criteria, outcomes, or analyses, will be communicated promptly to all relevant parties to ensure transparency and compliance with regulatory requirements.\u003c/p\u003e\n\u003cp\u003eProtocol amendments will be immediately communicated to all investigators and research team members through email notifications and team meetings, with detailed documentation of the changes provided, along with a rationale for the amendments and any implications for the study conduct.\u003c/p\u003e\n\u003cp\u003eFor Institutional Review Boards (IRBs), protocol amendments will be submitted for review and approval. The submission will include a summary of the changes, the rationale for the amendments, and any updated study documents, such as informed consent forms and data collection forms. Approval from the IRBs will be obtained before implementing any changes.\u003c/p\u003e\n\u003cp\u003eParticipants will be informed of any protocol amendments that may affect their participation or the study outcomes through verbal and written notifications. These notifications will include a clear explanation of the changes, the reasons behind them, and any potential impact on their involvement in the study. Updated informed consent forms will be provided if necessary.\u003c/p\u003e\n\u003cp\u003eSignificant protocol amendments will be updated in the trial registries where the study is registered, such as ClinicalTrials.gov, including a summary of the changes and the date of the amendment.\u003c/p\u003e\n\u003cp\u003eIf the protocol amendments have implications for previously published protocols or ongoing submissions, the relevant journals will be notified, with a detailed explanation of the changes and their potential impact on the study findings provided.\u003c/p\u003e\n\u003cp\u003eBy following this comprehensive communication plan, the research team ensures that all relevant parties are promptly and adequately informed of important protocol amendments, maintaining transparency and regulatory compliance throughout the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDissemination plans {31a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe dissemination of trial results will be carried out through a comprehensive communication strategy aimed at ensuring that all relevant parties are informed of the findings. Participants will be informed of the trial results through personalized letters or emails, which will provide a summary of the study findings, the implications for their health, and any follow-up actions or recommendations.\u003c/p\u003e\n\u003cp\u003eHealthcare professionals will be informed through presentations at medical conferences and meetings. Detailed findings will be published in peer-reviewed medical journals to ensure that clinicians and researchers have access to the data and can apply the findings in clinical practice.\u003c/p\u003e\n\u003cp\u003eThe trial results will be reported in relevant results databases, such as ClinicalTrials.gov, to ensure compliance with regulatory requirements and enhance transparency. Data sharing arrangements will be made with other researchers and institutions interested in conducting further analyses or secondary research, subject to data sharing agreements and ethical approvals.\u003c/p\u003e\n\u003cp\u003eThere will be no publication restrictions. The investigators will have the freedom to publish the trial results in a timely manner in accordance with the principles of academic freedom and scientific integrity. By following this dissemination plan, the research team ensure that trial results are effectively communicated to participants, healthcare professionals, the public, and other relevant groups, promoting transparency, knowledge sharing, and the application of research findings in practice.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCurrently, pharmacological treatments for fecal incontinence are limited to Psyllium and Loperamide. Many other treatments involve additional invasive procedures, highlighting the need for effective symptom management through simple oral medications\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Psyllium, being a granular formulation, poses difficulties for patients with swallowing disorders, while Loperamide carries the risk of severe constipation and toxic colitis\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e and has restrictions when used with cardiovascular medications\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Therefore, beyond demonstrating the superiority or non-inferiority of new drugs compared to existing ones, it is crucial to develop a broader range of pharmacological options for treating fecal incontinence.\u003c/p\u003e \u003cp\u003eIn general, comparative studies of pharmaceuticals typically involve evaluating the efficacy of two drugs against each other or comparing a drug's efficacy against a placebo. However, in this study, we aim to assess the performance of each drug using a pre-post comparison method and, as a secondary outcome, compare the two drugs. The rationale behind this approach is that demonstrating non-inferiority or superiority in the FISI change between the two drugs would require an excessively large initial sample size. Given that this is the first study on Ramosetron, we believe conducting a randomized parallel single-group pre-post test study as a preliminary research step is more prudent. This approach ensures patient safety and allows for a more efficient study design. Once the efficacy of Ramosetron is clearly demonstrated, we can then proceed to comparative studies with existing drugs. Using this method, we calculated that 74 patients per group, totaling 148 patients for both drug groups, would be necessary. This calculation aligns with the methodology used by Markland et al. in their 2015 study\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIf this study confirms the efficacy and safety of Ramosetron, it will significantly expand the treatment options available to clinicians, allowing for more tailored and comprehensive management plans for patients. The potential impact on clinical guidelines would be substantial, as it would provide a new oral medication option that could be safer and more effective for certain populations. Specifically, Ramosetron could be particularly beneficial for patients who have difficulty swallowing granular medications like Psyllium or those who experience severe side effects from Loperamide.\u003c/p\u003e \u003cp\u003e The confirmation of ramosetron\u0026rsquo;s efficacy and safety could lead to its inclusion in clinical guidelines for the treatment of fecal incontinence. This would provide an additional option for clinicians, enabling them to offer a medication that could be more suitable for patients with specific needs, such as those with cardiovascular comorbidities or those who are at risk for severe constipation and toxic colitis with Loperamide. If Ramosetron is shown to be effective, it could be recommended as a first-line or adjunctive treatment in managing fecal incontinence, particularly for patients who cannot tolerate current standard treatments.\u003c/p\u003e \u003cp\u003eBased on the results of this study, future research could focus on direct comparative studies between Ramosetron and existing treatments such as Loperamide. Additionally, further studies could explore the specific efficacy of Ramosetron in subgroups of patients, such as those with predominantly loose stools or those with cardiovascular comorbidities where Loperamide use is restricted. This could help to refine treatment protocols and ensure that patients receive the most appropriate and effective care based on their individual conditions and risk profiles.\u003c/p\u003e \u003cp\u003eIn conclusion, this study represents a critical step in expanding the pharmacological toolkit for treating fecal incontinence. By establishing the efficacy and safety of Ramosetron, we pave the way for more nuanced and effective management strategies, ultimately improving patient outcomes and quality of life.\u003c/p\u003e \u003cp\u003e \u003cb\u003eTrial status\u003c/b\u003e \u003c/p\u003e \u003cp\u003eOur trial protocol is currently at version 1.6, which was finalized on June 7, 2024. Recruitment for the trial began on January 19, 2024, and we anticipate that recruitment will be completed around June 2025.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e5-HT3 receptor antagonist : 5-hydroxytryptamine 3 receptor antagonist\u003c/p\u003e\n\u003cp\u003eBSS : Bristol stool scale\u003c/p\u003e\n\u003cp\u003eFI : Fecal incontinence\u003c/p\u003e\n\u003cp\u003eFISI : Fecal incontinence severity index\u003c/p\u003e\n\u003cp\u003eFIQL : Fecal incontinence Quality of Life\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJesung Park, Hong-min Ahn and Seung-Bum Ryoo contributed equally as the first authors\u003c/p\u003e\n\u003cp\u003eRumi Shin are recognized as corresponding authors, having jointly overseen the research and contributed to the study's correspondence and coordination\u003c/p\u003e\n\u003cp\u003eCorrespondence to\u003c/p\u003e\n\u003cp\u003eRumi Shin, MD, PhD\u003c/p\u003e\n\u003cp\u003eAssociate Professor\u003c/p\u003e\n\u003cp\u003eDivision of Colorectal Surgery, Department of Sugery, Seoul National University Boramae Medical Center\u003c/p\u003e\n\u003cp\u003e20, Boramae-ro 5-gil, Dongjak-gu, Seoul, 07061, South Korea\u003c/p\u003e\n\u003cp\u003eE-mail: [email protected]\u003c/p\u003e\n\u003cp\u003eSupported by grant from the Seoul National University College of Medicine Research foundation\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions {31b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eJesung Park, Hong-min Ahn and Seung-Bum Ryoo\u003c/strong\u003e contributed equally as the \u003cstrong\u003efirst authors\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRumi Shin\u003c/strong\u003e are recognized as corresponding authors, having jointly overseen the research and contributed to the study's \u003cstrong\u003ecorrespondence and coordination\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJesung Park and Hong-min Ahn were responsible for the conceptualization and design of the study, as well as drafting the initial manuscript. Yungyeong Oh and Jin sun Choi conducted the data collection and management. Heung-Kwon Oh, Rumi Shin, and Seung-Bum Ryoo supervised the study and provided overall guidance. All authors read and approved the final manuscript.\u003cbr\u003e \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding {4}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was supported by a grant of the Korean cancer survivors Healthcare R\u0026amp;D Project through the National Cancer Center, funded by the Ministry of Health \u0026amp; Welfare, Republic of Korea (RS-2023-CC140143)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials {29}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. There are no contractual agreements that limit access to the data for any of the investigators involved in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate {24}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Institutional Review Board (IRB) of Seoul National University Hospital, under the reference number 2303-158-1417. Written informed consent to participate in the study was obtained from all participants. For participants under the age of 18, consent was obtained from their parents or legal guardians.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication {32}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests {28}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003cbr\u003e \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u003c/strong\u003e\u003cstrong\u003e’ \u003c/strong\u003e\u003cstrong\u003einformation (optional) \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJesung Park, MD. PhD.\u003csup\u003e1*\u003c/sup\u003e, Hong-Min Ahn, MD.\u003csup\u003e 4*\u003c/sup\u003e, Seung-Bum Ryoo MD. PhD.\u003csup\u003e1,2*\u003c/sup\u003e, Yungyeong Oh\u003csup\u003e1\u003c/sup\u003e, Jin Sun Choi, MD.\u003csup\u003e3\u003c/sup\u003e, Heung-Kwon Oh MD. PhD.\u003csup\u003e4\u003c/sup\u003e, Rumi Shin MD. PhD.\u003csup\u003e3\u003c/sup\u003e\u003csup\u003e†\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e1. Department of Surgery, Seoul National University hospital, Seoul, Republic of Korea\u003c/p\u003e\n\u003cp\u003e2. Department of Surgery, Seoul National College of Medicine, Seoul, Republic of Korea\u003c/p\u003e\n\u003cp\u003e3. Department of Surgery, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea\u003c/p\u003e\n\u003cp\u003e4. Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Republic of Korea\u003c/p\u003e\n\u003cp\u003e*Co-first author, †Corresponding author\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eShah R, Villanueva Herrero JA. Fecal Incontinence. \u003cem\u003eStatPearls\u003c/em\u003e. 2024.\u003c/li\u003e\n\u003cli\u003eMenees S, Chey WD. Fecal Incontinence: Pathogenesis, Diagnosis, and Updated Treatment Strategies. \u003cem\u003eGastroenterol Clin North Am\u003c/em\u003e. Mar 2022;51(1):71-91. doi:10.1016/j.gtc.2021.10.005\u003c/li\u003e\n\u003cli\u003eNg KS, Sivakumaran Y, Nassar N, Gladman MA. Fecal Incontinence: Community Prevalence and Associated Factors--A Systematic Review. \u003cem\u003eDis Colon Rectum\u003c/em\u003e. Dec 2015;58(12):1194-209. doi:10.1097/dcr.0000000000000514\u003c/li\u003e\n\u003cli\u003eAitola P, Lehto K, Fonsell R, Huhtala H. Prevalence of faecal incontinence in adults aged 30 years or more in general population. \u003cem\u003eColorectal Dis\u003c/em\u003e. Jul 2010;12(7):687-91. doi:10.1111/j.1463-1318.2009.01878.x\u003c/li\u003e\n\u003cli\u003ePasricha T, Staller K. Fecal Incontinence in the Elderly. \u003cem\u003eClin Geriatr Med\u003c/em\u003e. Feb 2021;37(1):71-83. doi:10.1016/j.cger.2020.08.006\u003c/li\u003e\n\u003cli\u003eRey E, Choung RS, Schleck CD, Zinsmeister AR, Locke GR, Talley NJ. Onset and risk factors for fecal incontinence in a US community. \u003cem\u003eAm J Gastroenterol\u003c/em\u003e. Feb 2010;105(2):412-9. doi:10.1038/ajg.2009.594\u003c/li\u003e\n\u003cli\u003eDitah I, Devaki P, Luma HN, et al. Prevalence, trends, and risk factors for fecal incontinence in United States adults, 2005-2010. \u003cem\u003eClin Gastroenterol Hepatol\u003c/em\u003e. Apr 2014;12(4):636-43.e1-2. doi:10.1016/j.cgh.2013.07.020\u003c/li\u003e\n\u003cli\u003eOmar MI, Alexander CE. Drug treatment for faecal incontinence in adults. \u003cem\u003eCochrane Database Syst Rev\u003c/em\u003e. Jun 11 2013;2013(6):CD002116. doi:10.1002/14651858.CD002116.pub2\u003c/li\u003e\n\u003cli\u003eNorton C, Chelvanayagam S, Wilson-Barnett J, Redfern S, Kamm MA. Randomized controlled trial of biofeedback for fecal incontinence. \u003cem\u003eGastroenterology\u003c/em\u003e. Nov 2003;125(5):1320-9. doi:10.1016/j.gastro.2003.09.039\u003c/li\u003e\n\u003cli\u003eHeymen S, Scarlett Y, Jones K, Ringel Y, Drossman D, Whitehead WE. Randomized controlled trial shows biofeedback to be superior to pelvic floor exercises for fecal incontinence. \u003cem\u003eDis Colon Rectum\u003c/em\u003e. Oct 2009;52(10):1730-7. doi:10.1007/DCR.0b013e3181b55455\u003c/li\u003e\n\u003cli\u003eMaeda Y, Laurberg S, Norton C. Perianal injectable bulking agents as treatment for faecal incontinence in adults. \u003cem\u003eCochrane Database Syst Rev\u003c/em\u003e. Feb 28 2013;(2):CD007959. doi:10.1002/14651858.CD007959.pub3\u003c/li\u003e\n\u003cli\u003eBravo Gutierrez A, Madoff RD, Lowry AC, Parker SC, Buie WD, Baxter NN. Long-term results of anterior sphincteroplasty. \u003cem\u003eDis Colon Rectum\u003c/em\u003e. May 2004;47(5):727-31; discussion 731-2. doi:10.1007/s10350-003-0114-6\u003c/li\u003e\n\u003cli\u003eWexner SD, Coller JA, Devroede G, et al. Sacral nerve stimulation for fecal incontinence: results of a 120-patient prospective multicenter study. \u003cem\u003eAnn Surg\u003c/em\u003e. Mar 2010;251(3):441-9. doi:10.1097/SLA.0b013e3181cf8ed0\u003c/li\u003e\n\u003cli\u003eJelovsek JE, Markland AD, Whitehead WE, et al. Controlling faecal incontinence in women by performing anal exercises with biofeedback or loperamide: a randomised clinical trial. \u003cem\u003eLancet Gastroenterol Hepatol\u003c/em\u003e. Sep 2019;4(9):698-710. doi:10.1016/s2468-1253(19)30193-1\u003c/li\u003e\n\u003cli\u003eMarkland AD, Burgio KL, Whitehead WE, et al. Loperamide Versus Psyllium Fiber for Treatment of Fecal Incontinence: The Fecal Incontinence Prescription (Rx) Management (FIRM) Randomized Clinical Trial. \u003cem\u003eDis Colon Rectum\u003c/em\u003e. Oct 2015;58(10):983-93. doi:10.1097/dcr.0000000000000442\u003c/li\u003e\n\u003cli\u003eBliss DZ, Jung HJ, Savik K, et al. Supplementation with dietary fiber improves fecal incontinence. \u003cem\u003eNurs Res\u003c/em\u003e. 2001;50(4):203-13. doi:10.1097/00006199-200107000-00004\u003c/li\u003e\n\u003cli\u003eStaller K, Song M, Grodstein F, et al. Increased Long-term Dietary Fiber Intake Is Associated With a Decreased Risk of Fecal Incontinence in Older Women. \u003cem\u003eGastroenterology\u003c/em\u003e. Sep 2018;155(3):661-667.e1. doi:10.1053/j.gastro.2018.05.021\u003c/li\u003e\n\u003cli\u003eWu PE, Juurlink DN. Clinical Review: Loperamide Toxicity. \u003cem\u003eAnn Emerg Med\u003c/em\u003e. Aug 2017;70(2):245-252. doi:10.1016/j.annemergmed.2017.04.008\u003c/li\u003e\n\u003cli\u003eMcGregor A, Brown M, Thway K, Wright SG. Fulminant amoebic colitis following loperamide use. \u003cem\u003eJ Travel Med\u003c/em\u003e. 2007;14(1):61-2. doi:10.1111/j.1708-8305.2006.00096.x\u003c/li\u003e\n\u003cli\u003eScarlett Y. Medical management of fecal incontinence. \u003cem\u003eGastroenterology\u003c/em\u003e. Jan 2004;126(1 Suppl 1):S55-63. doi:10.1053/j.gastro.2003.10.007\u003c/li\u003e\n\u003cli\u003eTomita T, Fukui H, Morishita D, et al. Efficacy of Serotonin Type 3 Receptor Antagonist Ramosetron on Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D)-Like Symptoms in Patients with Quiescent Inflammatory Bowel Disease: A Randomized, Double-Blind, Placebo-Controlled Trial. \u003cem\u003eJ Clin Med\u003c/em\u003e. Nov 22 2022;11(23)doi:10.3390/jcm11236882\u003c/li\u003e\n\u003cli\u003eQi Q, Zhang Y, Chen F, Zuo X, Li Y. Ramosetron for the treatment of irritable bowel syndrome with diarrhea: a systematic review and meta-analysis of randomized controlled trials. \u003cem\u003eBMC Gastroenterol\u003c/em\u003e. Jan 8 2018;18(1):5. doi:10.1186/s12876-017-0734-2\u003c/li\u003e\n\u003cli\u003eFukudo S, Kinoshita Y, Okumura T, et al. Effect of ramosetron in female patients with irritable bowel syndrome with diarrhea: a phase III long-term study. \u003cem\u003eJ Gastroenterol\u003c/em\u003e. Sep 2016;51(9):874-82. doi:10.1007/s00535-016-1165-5\u003c/li\u003e\n\u003cli\u003eMin YW, Rhee PL. The clinical potential of ramosetron in the treatment of irritable bowel syndrome with diarrhea (IBS-D). \u003cem\u003eTherap Adv Gastroenterol\u003c/em\u003e. May 2015;8(3):136-42. doi:10.1177/1756283X15572580\u003c/li\u003e\n\u003cli\u003eRyoo SB, Park JW, Lee DW, et al. Anterior resection syndrome: a randomized clinical trial of a 5-HT3 receptor antagonist (ramosetron) in male patients with rectal cancer. \u003cem\u003eBr J Surg\u003c/em\u003e. Jun 22 2021;108(6):644-651. doi:10.1093/bjs/znab071\u003c/li\u003e\n\u003cli\u003eKoo HL, Koo DC, Musher DM, DuPont HL. Antimotility agents for the treatment of Clostridium difficile diarrhea and colitis. \u003cem\u003eClin Infect Dis\u003c/em\u003e. Mar 01 2009;48(5):598-605. doi:10.1086/596711\u003c/li\u003e\n\u003cli\u003eWald A, Bharucha AE, Limketkai B, et al. ACG Clinical Guidelines: Management of Benign Anorectal Disorders. \u003cem\u003eAm J Gastroenterol\u003c/em\u003e. Oct 01 2021;116(10):1987-2008. doi:10.14309/ajg.0000000000001507\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"trials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"trls","sideBox":"Learn more about [Trials](http://trialsjournal.biomedcentral.com/)","snPcode":"13063","submissionUrl":"https://www.editorialmanager.com/trls","title":"Trials","twitterHandle":"MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Fecal incontinence, 5-HT3 receptor antagonist, Ramosetron, Psyllium, Fecal Incontinence Severity Index","lastPublishedDoi":"10.21203/rs.3.rs-5153650/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5153650/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Fecal incontinence (FI) is a prevalent condition affecting 2% to 21% of the general population, with higher rates in older adults and specific settings such as nursing homes and hospitals. Current treatments include supportive care, biofeedback, anal injections, and sacral nerve stimulation, though these can be invasive or costly. Pharmacological therapies, like stool bulking agents and constipating agents, help manage symptoms but can have side effects. Ramosetron, a 5-HT3 receptor antagonist, shows promise for FI treatment by reducing intestinal motility and improving stool consistency. This study aims to compare the effectiveness and safety of Ramosetron (Irribow®) and AGIO granules (AGIO®) in treating FI.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: This study will include adults aged 19 and above diagnosed with FI. Participants will be randomly assigned to receive either Ramosetron (5μg for males, 2.5μg for females) or Psyllium (6g) once daily. The primary endpoint will compare changes in Fecal Incontinence Severity Index (FISI) scores before and after medication. Secondary endpoints will include comparisons of FISI scores, Fecal Incontinence Quality of Life (FIQL) scores, patient satisfaction surveys, and Bristol Stool Scale scores between the two groups. Follow-up visits will occur before treatment, and at 1, 4, and 12 months to assess symptoms and administer surveys. A sample size of 56 participants is needed for statistical significance at a 0.05 level with 0.8 power, accounting for dropout, totaling 148 participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion\u003c/strong\u003e: It is believed that 5-HT3 receptor antagonists, along with Psyllium, can improve bowel habits and alleviate symptoms, thereby enhancing the quality of life for patients with FI.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration\u003c/strong\u003e: ClinicalTrials.gov NCT06166615, December 12, 2023\u003c/p\u003e","manuscriptTitle":"The Safety and Efficacy of Ramosetron versus Psyllium for the Treatment of Fecal Incontinence (SERAFI) : Study protocol for a randomized trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-15 10:28:00","doi":"10.21203/rs.3.rs-5153650/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-08-03T16:56:51+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-09T11:32:17+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-11T08:20:41+00:00","index":"","fulltext":""},{"type":"submitted","content":"Trials","date":"2025-03-11T04:18:13+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"trials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"trls","sideBox":"Learn more about [Trials](http://trialsjournal.biomedcentral.com/)","snPcode":"13063","submissionUrl":"https://www.editorialmanager.com/trls","title":"Trials","twitterHandle":"MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"50c6f4e1-e9fb-4ef7-8086-3ed113552a54","owner":[],"postedDate":"May 15th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-11-10T16:06:12+00:00","versionOfRecord":{"articleIdentity":"rs-5153650","link":"https://doi.org/10.1186/s13063-025-09165-2","journal":{"identity":"trials","isVorOnly":false,"title":"Trials"},"publishedOn":"2025-11-05 15:57:19","publishedOnDateReadable":"November 5th, 2025"},"versionCreatedAt":"2025-05-15 10:28:00","video":"","vorDoi":"10.1186/s13063-025-09165-2","vorDoiUrl":"https://doi.org/10.1186/s13063-025-09165-2","workflowStages":[]},"version":"v1","identity":"rs-5153650","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5153650","identity":"rs-5153650","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}