Evaluation on Fufang Congrong Yizhi Capsules (FCYC) of cognitive impairment after robot-assisted neurosurgery treatment for intracerebral hemorrhage (CONPAIR) : study protocol for a randomized controlled trial

Evaluation on Fufang Congrong Yizhi Capsules (FCYC) of cognitive impairment after robot-assisted neurosurgery treatment for intracerebral hemorrhage (CONPAIR) : study protocol for a randomized controlled 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 Evaluation on Fufang Congrong Yizhi Capsules (FCYC) of cognitive impairment after robot-assisted neurosurgery treatment for intracerebral hemorrhage (CONPAIR) : study protocol for a randomized controlled trial Mengting Mo, Wengang Wang, Mingjing Lu, Junhui Zhao, Shengyong Wang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5901671/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Intracerebral hemorrhage (ICH) is associated with high mortality and disability rates, which places a significant social burden. Robot-assisted neurosurgery with precise positioning and high stability has become an important advance in the development of minimally invasive surgery for ICH. Cognitive impairment is a common complication in patients with ICH, which seriously affects the stroke rehabilitation process. We are not sure about the medication treatment for cognitive impairment after robot-assisted neurosurgery treatment for ICH. In this CONPAIR trial, we will evaluate the safety and efficacy of Fufang Congrong Yizhi Capsules (FCYC) for cognitive impairment after robot-assisted neurosurgery treatment for ICH. Methods and analysis In this multicentrer, randomized, controlled trial involving patients with cognitive impairment after robot-assisted neurosurgery treatment for ICH, we assessed medical management. Two hundred patients will be randomly assigned, in a 1:1 ratio, to either an experimental group or a control group. The experimental group will receive conventional treatment and oral administration of FCYC for 12 weeks or the control group will receive only conventional treatment. The primary safety end point was death within 30 days after enrollment. Ethics and management The Case Report Form (CRF) will be completed and signed by well-trained researchers. We will monitor and promptly report adverse events throughout the trial. The privacy and data of the subjects will be safeguarded. Research Ethics Board approval has been obtained. ClinicalTrials.gov number NCT06673602 Clinical Research Protocol Cognitive impairment Intracerebral hemorrhage Fufang Congrong Yizhi Capsules Robot-assisted neurosurgery Figures Figure 1 BACKGROUND Intracerebral hemorrhage (ICH), accounting for 10–20% of all strokes, has a high case fatality rate and disability rate, imposing a heavy burden on families and society. [ 1 – 4 ] After the initial hemorrhage, hematoma expansion and perihematoma edema cause secondary brain damage and a poor prognosis, so the primary objective of ICH surgery is to remove the hematoma and lower intracranial pressure. [ 5 – 6 ] In recent years, neurosurgical robots have developed rapidly due to the advancements in neuroimaging and robotics technologies. The advantages of robotic surgery include precise positioning, a shorter operative time, and greater stability. [ 7 – 8 ] A clinical study of 142 patients observed that the prognosis of neurological function was better in the robotic surgery group than in the neuro-endoscopic surgery group. [ 9 ] A systematic review and meta-analysis revealed that robot-assisted neurosurgery is a safe and effective approach that outperforms conventional surgery or conservative treatment in terms of rebleeding rates, intracranial infection rates, and neurological function improvement. [ 10 ] Robot-assisted neurosurgery has been a significant advancement in the surgical treatment of ICH. [ 11 ] Cognitive impairment is a common complication in patients with ICH, with about 19%-63.3% of patients experiencing it within four years of ICH onset, which seriously affects the patients’ average lifespan and quality of life. [ 12 – 16 ] Current research mainly focuses on motor function recovery after ICH, but cognitive recovery, especially after robot-assisted neurosurgery treatment for ICH, has received relatively less attention. [ 17 – 19 ] The Fufang Congrong Yizhi Capsules (FCYC), widely used in the long-term combined treatment of vascular dementia (VaD) and vascular cognitive impairment (VCI) with remarkable efficacy, has been documented in the guidelines and expert consensus. [ 20 ] Network pharmacology revealed that FCYC can treat cognitive impairment through multi-component, multi-target, and multi-pathway. [ 21 ] A randomized controlled trial has demonstrated that FCYC can enhance cognitive function in individuals with mild to moderate Alzheimer's disease (AD), especially in the cognitive domains of episodic memory and visual-spatial processing ability, and can regulate the clinical physicochemical indexes related to energy metabolism in the brain. [ 22 ] A systematic review with trial sequential analysis and GRADE Assessment indicates that combining of FCYC with cognition-modifying Western medicine can improve cognitive function and activities of daily living, and alleviate mental and behavioral symptoms in AD patients. [ 23 ] In this CONPAIR trial, we will evaluate the security and effectiveness of FCYC in cognitive impairment after robot-assisted neurosurgery treatment for ICH, and discover new pathways for disease prevention and treatment. METHODS AND ANALYSIS Research objectives The primary objective is to observe the safety and efficacy of FCYC of cognitive impairment after robot-assisted neurosurgery treatment for ICH. The secondary objective is to decipher the contributing factors to cognitive impairment and its impact on outcomes, including patients' characteristics, level of blood pressure, Magnetic Resonance Imaging (MRI) imaging features, and blood proteomics. Study design This is a randomized, controlled clinical study conducted across multiple centers. To avoid regional differences, the research will take place in 6 hospitals located in various regions of China. This study will be conducted in adherence to the Declaration of Helsinki and the guidelines of Good Clinical Practice (GCP). We will recruit patients who meet the inclusion criteria and do not meet the exclusion criteria, to establish a cohort comprising 200 participants with cognitive impairment after robot-assisted neurosurgery treatment for ICH. Participants will sign a consent form and then be randomized into either the experimental or control group. The study design is shown in Fig 1. Eligibility criteria Eligible patients are those who fulfill all of the following inclusion criteria and do not have any listed exclusion criteria. Diagnostic criteria （1）Meet the diagnostic criteria for ICH according to “Chinese guidelines for diagnosis and treatment of acute intracerebral hemorrhage 2019” [24] ; （2）Meet the diagnostic criteria for post-stroke cognitive impairment (PSCI) according to “European Stroke Organisation and European Academy of Neurology joint guidelines on post-stroke cognitive impairment” [12] ; （3）Meet the traditional Chinese medicine (TCM) diagnostic criteria for deficiency of the liver and kidney, phlegm and stagnant blood obstructing the meridians pattern. Inclusion criteria （1）Meet the diagnostic criteria of ICH and use robot-assisted neurosurgery to treat ICH; （2）Meet diagnostic criteria for PSCI; （3）Meet diagnosis of deficiency of the liver and kidney, phlegm and stagnant blood obstructing the meridians pattern; （4）Aged 18 and above; （5）Not limit gender; （6）2 weeks after robot-assisted neurosurgery; （7）The participants exhibit a clear consciousness, possess normal visual and auditory capabilities, and are capable of participating in neuropsychological evaluations; （8）Submit informed consent. Exclusion criteria (1) Other types of dementia besides VaD, such as AD, dementia with Lewy bodies (DLB), and frontotemporal dementia; (2) Patients with other diseases that can affect cognitive function, such as Parkinson's disease (PD), normal pressure hydrocephalus (iNPH), brain tumor, encephalitis, thyroid dysfunction, severe anemia, syphilis, and acquired immune deficiency syndrome(AIDS); (3) Patients experiencing severe visual or auditory impairments, apraxia, aphasia, or apparent neurological abnormalities, who are unable to cooperate with examinations; (4) Patients with communication difficulties, patients with a history of mental disorders； (5) Patients with depression disorder, Hamilton Depression Scale ( HAMD ) ≥ 17 points; (6) Patients diagnosed with alcohol or drug dependency within the past six months; (7) Patients suffering from severe hepatic and renal dysfunction, heart failure or other serious primary diseases; (8) Preconceptional, lactating, and pregnant women. Randomization scheme In this study, subjects will be enrolled in a centralized administration program. All subjects will be enrolled consecutively and randomized into the experimental or control groups (1:1). The randomization number and grouping will be conveyed to the sub-center principal investigator (PI) by the center PI at the time of patient enrollment. Robotic Surgery Operations (1) Preoperative localization: On the day of surgery, perform cranial Computed tomography (CT) at the Radiology Department after the insertion of five bone nails. Then plaster three or four MRAKs on the head surface to encircle the lesion. Ensure that three MRAKs are not collinear, and four MRAKs are not coplanar. Subsequently, the localized image data, including cranial Computed tomography angiography (CTA) with a 1 mm layer thickness, should be imported into a computer system. (2) Use computer surgical planning software to make an operative plan, outline the lesion, confirm surgical target and puncture paths, and display 3D images. Use a 3-pin head immobilization device to secure the patient's head. Perform 3D structured light registration or markers registration. Check that the positioning accuracy is within 1 mm. Then, register the patient and the robotic arm. In succession, click on [Target Lock]-[Target Registration]-[Surgical Simulation]-[Robotic Arm Positioning]. Then, click the path of "Verify Target," select [Target Lock]-[Target Registration]-[Surgical Simulation]-[Positioning], check the path arrival. The robotic arm automatically positions itself at the verification point. Check that the positioning accuracy is within 1 mm. (3) Anesthesia: The choice between local anesthesia and general anesthesia depends on the patient's condition. (4) Disinfection and draping: The surgical area must be sterilized, after which sterile drapes should be draped. Place a sterile bag onto the robotic arm and install the sterile guider and adapter. (5) Surgery: The incision for the surgery follows the path determined by robotic planning. The scalp is incised for approximately 3 centimeters before drilling into the skull. The puncture is executed along the robot's predetermined path, and a drain is subsequently placed along the channel leading to the target location. The volume of aspirated hematoma amounts to 90% of the preoperative calculation. The drain is maneuvered beneath the skin for a distance of 2cm, then threaded through the skin and secured in place. (6) After the surgery, the scalp is sutured in layers, sterilized, and bandaged again, and then patients are sent to the postoperative room. Intervention The control group participants receive conventional treatment, while the experimental group participants receive conventional treatment combined with oral administration of FCYC (four capsules, three times a day) for a 12-week course of treatment. Follow-up and points of data capture The points of follow-up visits in the trial are as follows: 3 months ± 7 days, 6 months ± 14 days, and 12 months ± 14 days after enrolment. The visits will be conducted by trained professionals at each center. These items will be documented during subsequent follow-up visits, including (1) the National Institutes of Health Stroke Scale (NIHSS), the modified Rankin scale (mRS), and perioperative Brain Function Assessment Scale; (2) follow-up events: all-cause death/vasogenic death/non-vasogenic death, recurrent stroke, myocardial infarction/heart failure, endovascular operation or surgery; (3) secondary prevention drug compliance; (4) management of blood pressure; (5) adverse events. In addition, Safety indicators, cranial MRI, blood proteomics, and TCM syndrome evaluation scale are performed at only the first follow-up and enrolment. Outcome measures The primary efficacy outcome of this study is the change in test scores on the Perioperative Brain Function Assessment Scale after 12 weeks of treatment compared to baseline values. The Perioperative Brain Function Assessment Scale comprises several scales, including the Montreal Cognitive Assessment (MoCA), the Mini-Mental State Examination (MMSE), the Verbal Fluency Test (VFT), the Boston Naming Test-15 (BNT-15), the Chinese Auditory Learning Test (CAVLT), the Digital Span Test (DST), the Symbol Digit Modalities Test (SDMT), the Stroop Color-Word Test (Stroop-CWT), the Color Trails Test (CTT), the Rey Complex Figure Test(RCFT), HAMD, the Hamilton Anxiety Scale(HAMA), the Pittsburgh Sleep Quality Index(PSQI), and the Activities of daily living (ADL). The secondary efficacy endpoints include changes in test scores on the NIHSS, the mRS, and the TCM syndrome evaluation scale. Additional information includes demographics, blood pressure and blood lipid levels, MRI imaging features, and blood proteomics. Safety indexes consist of vital signs, laboratory examinations (blood routine, urine test, and hepatorenal assessment), electrocardiogram, and adverse events. Procedures and variables After participants sign the consent form, the researchers register their basic information, demographics, medical history, and previous medication use. Subsequently, the patients undergo a series of medical tests, including blood pressure, electrocardiogram, blood and urine tests, MRI(3D T1 (mprage 1mm）+T2+FLAIR+DWI+SWI+MRA (3D TOF)), blood proteomics (ApoE、GFAP、NEFL、GDF15) and relevant scales. Relevant scales and data capture will be completed at each follow-up visit. Follow-up appointments are scheduled at the end of each visit. The schedule of procedures and variable collection for the trial is presented in Table 1. Sample size estimation Sample size estimation was based on the primary efficacy measures. Based on the results of the previous study, each group should have 80 participants, with a significance level of α at 0.05 for a two-tailed test and a power (1-β) at 0.80. Considering a 20% drop-out rate, the final sample size is 100 cases in the test group and 100 cases in the control group, totaling 200 cases. Statistical analysis SAS software will be used for statistical analysis. All statistical analyses will be performed using two-sided tests or 95% confidence intervals at a 5% significance level. For quantitative data, t-test and one-way ANOVA will be used. Nonparametric data will be analyzed through the Mann-Whitney test, while categorical data will be evaluated using either the chi-squared test or the chi-squared test for trend. The study will evaluate primary efficacy indicators using analysis of covariance (ANCOVA). Survival analysis will be conducted using the Cox proportional-hazards model. Multivariate analysis will be performed using unconditional logistic regression. Correlation analysis will utilize the Spearman correlation test. Number of centers There are six participating organizations: Qinhuangdao Hospital of Traditional Chinese Medicine, Tsinghua University Yuquan Hospital, Kunming Sanbo Brain Hospital, Weifang Hospital of Traditional Chinese Medicine, Kaifeng Third People's Hospital, Shandong Public Health Clinical Center. Ethics and mangement Data recording and management For each enrolled subject, a Case Report Form (CRF) will be completed and signed by the well-trained researchers. This also applies to records for patients who fail to complete the study. If a participant withdraws from the study, the reason must be noted on the CRF. All study-related files, including consent forms, the CRF, questionnaires, medical records, and other records, will be stored in a locked space or on a password-protected computer in each hospital for three years after the study is completed. Researchers must adhere to professional confidentiality rules and maintain the confidentiality of all personal identity and medical information about their patients. A designated person is responsible for managing the original research materials. Independent clinical research associates (CRA) will regularly audit and monitor the study at each hospital. Safety and adverse events In this study, adverse reactions may occur in individuals taking the oral medication FCYC. Adverse reactions are primarily concentrated in the digestive system, with symptoms such as nausea, emesis, abdominal pain, diarrhea, epigastric distension, and decreased appetite. Other systemic symptoms may encompass palpitation and skin pruritus, etc. These adverse reactions are generally mild and can be alleviated by discontinuing the use of FCYC. Adverse events must be recorded on the CRF as they occur. Each event should be described in detail, including start and end dates, severity, relationship to the therapy as judged by the investigator, action taken, and outcome. Reporting serious adverse events and unanticipated problems to the ethics board, competent authorities, sponsors, and drug regulatory agencies is required on time. The principal investigator should perform periodic cumulative reviews of all adverse events and hold investigator meetings as necessary to assess the risks and benefits of the study. Ethical considerations The study has been approved by the ethics committee of Qinhuangdao Hospital, Dongfang Hospital Beijing University of Chinese Medicine (Ethics approval number: 202311A), and has been registered at Clinicaltrials.gov with the identifier: NCT06673602. The investigator is responsible for fully informing subjects or their legal representatives about the purpose, procedures, and potential risks of the study, as well as providing information on alternative treatments. Subjects have the right to withdraw from the study at any time. Ensure that subjects are fully informed, have sufficient time to consider and voluntarily choose to consent to participation in the study. Avoid any inappropriate inducement of subjects. Before the study commences, participants will sign a written informed consent. The privacy and data of the subjects will be safeguarded throughout the study. Abbreviations ICH Intracerebral hemorrhage FCYC Fufang Congrong Yizhi Capsules CRF Case Report Form VaD Vascular dementia VCI Vascular cognitive impairment AD Alzheimer's disease MRI Magnetic Resonance Imaging GCP Good Clinical Practice PSCI Post-stroke cognitive impairment TCM Traditional Chinese medicine DLB Dementia with Lewy bodies PD Parkinson's disease iNPH Normal pressure hydrocephalus AIDS Acquired immune deficiency syndrome HAMD Hamilton Depression Scale PI Principal investigator CT Computed tomography CTA Computed tomography angiography NIHSS National Institutes of Health Stroke Scale mRS Modified Rankin scale MoCA Montreal Cognitive Assessment MMSE Mini-Mental State Examination VFT Verbal Fluency Test BNT-15 Boston Naming Test-15 CAVLT Chinese Auditory Learning Test DST Digital Span Test SDMT Symbol Digit Modalities Test Stroop-CWT Stroop Color-Word Test CTT Color Trails Test RCFT Rey Complex Figure Test PSQI Pittsburgh Sleep Quality Index ADL Activities of daily living CRA Clinical research associates Declarations Acknowledgements We thank the participants for their involvement. Author contributions QZ design the trial and participate in all phases of the study. WW assists with management. Patients are enrolled and observed in subcenters by WW, ML, JZ, SW, JR, and MZ. Data analysis and statistics by MM. All authors read and approved the final manuscript. Funding This study is funded by CHNI Traditional Chinese Medicine Development Center(ZW2023A005) and Lei Yun Shang Pharmaceutical Group Co., Ltd. Ethics approval and consent to participate The study was approved by the local ethics committee of the Qinhuangdao Hospital, Dongfang Hospital Beijing University of Chinese Medicine (Ethics approval number: 202311A). Consent for publication Consent for publication has been obtained from Qinhuangdao Hospital, Dongfang Hospital Beijing University of Chinese Medicine. Competing interests The authors declare that there is no conflict of interest regarding the publication of this article. Author details 1 Department of Neurology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China. 2 Department of Neurology, Qinhuangdao Hospital, Dongfang Hospital Beijing University of Chinese Medicine, Qinhuangdao, Hebei, China. 3 The Faculty of Medicine, Qilu Institute of Technology, Jinan, Shandong, China. 4 Department of Anesthesiology, Weifang Hospital of Traditional Chinese Medicine, Weifang, Shandong, China. 5 Department of Neurosurgery, Kaifeng Third People's Hospital, Kaifeng, Henan, China. 6 Department of Neurosurgery, Kunming Sanbo Brain Hospital, Kunming, Yunnan, China. 7 Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, China. 8 Department of Neurosurgery, Tsinghua University Yuquan Hospital, Beijing, China. References An SJ, Kim TJ, Yoon BW. Epidemiology, Risk Factors, and Clinical Features of Intracerebral Hemorrhage: An Update. J Stroke. 2017;19(1):3-10. doi: 10.5853/jos.2016.00864. 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FCYC: Fufang Congrong Yizhi Capsules\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5901671/v1/f9eb4ffb8ffbbac54c0d09c2.png"},{"id":75409631,"identity":"f751f2c0-1ca7-448d-919d-5619ae000ae6","added_by":"auto","created_at":"2025-02-04 09:04:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":800153,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5901671/v1/c5908a63-d85d-4b18-806e-79fc942a2a6f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Evaluation on Fufang Congrong Yizhi Capsules (FCYC) of cognitive impairment after robot-assisted neurosurgery treatment for intracerebral hemorrhage (CONPAIR) : study protocol for a randomized controlled trial","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eIntracerebral hemorrhage (ICH), accounting for 10\u0026ndash;20% of all strokes, has a high case fatality rate and disability rate, imposing a heavy burden on families and society.\u003csup\u003e[\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e After the initial hemorrhage, hematoma expansion and perihematoma edema cause secondary brain damage and a poor prognosis, so the primary objective of ICH surgery is to remove the hematoma and lower intracranial pressure.\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e In recent years, neurosurgical robots have developed rapidly due to the advancements in neuroimaging and robotics technologies. The advantages of robotic surgery include precise positioning, a shorter operative time, and greater stability. \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003eA clinical study of 142 patients observed that the prognosis of neurological function was better in the robotic surgery group than in the neuro-endoscopic surgery group.\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e A systematic review and meta-analysis revealed that robot-assisted neurosurgery is a safe and effective approach that outperforms conventional surgery or conservative treatment in terms of rebleeding rates, intracranial infection rates, and neurological function improvement.\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e Robot-assisted neurosurgery has been a significant advancement in the surgical treatment of ICH.\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e Cognitive impairment is a common complication in patients with ICH, with about 19%-63.3% of patients experiencing it within four years of ICH onset, which seriously affects the patients\u0026rsquo; average lifespan and quality of life.\u003csup\u003e[\u003cspan additionalcitationids=\"CR13 CR14 CR15\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e Current research mainly focuses on motor function recovery after ICH, but cognitive recovery, especially after robot-assisted neurosurgery treatment for ICH, has received relatively less attention.\u003csup\u003e[\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e The Fufang Congrong Yizhi Capsules (FCYC), widely used in the long-term combined treatment of vascular dementia (VaD) and vascular cognitive impairment (VCI) with remarkable efficacy, has been documented in the guidelines and expert consensus.\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e Network pharmacology revealed that FCYC can treat cognitive impairment through multi-component, multi-target, and multi-pathway.\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e A randomized controlled trial has demonstrated that FCYC can enhance cognitive function in individuals with mild to moderate Alzheimer's disease (AD), especially in the cognitive domains of episodic memory and visual-spatial processing ability, and can regulate the clinical physicochemical indexes related to energy metabolism in the brain.\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e A systematic review with trial sequential analysis and GRADE Assessment indicates that combining of FCYC with cognition-modifying Western medicine can improve cognitive function and activities of daily living, and alleviate mental and behavioral symptoms in AD patients.\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e In this CONPAIR trial, we will evaluate the security and effectiveness of FCYC in cognitive impairment after robot-assisted neurosurgery treatment for ICH, and discover new pathways for disease prevention and treatment.\u003c/p\u003e"},{"header":"METHODS AND ANALYSIS","content":"\u003cp\u003e\u003cstrong\u003eResearch objectives\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary objective is to observe the safety and efficacy of FCYC of cognitive impairment after robot-assisted neurosurgery treatment for ICH. The secondary objective is to decipher the contributing factors to cognitive impairment and its impact on outcomes, including patients\u0026apos; characteristics, level of blood pressure, Magnetic Resonance Imaging (MRI) imaging features, and blood proteomics.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis is a randomized, controlled clinical study conducted across multiple centers. To avoid regional differences, the research will take place in 6 hospitals located in various regions of China. This study will be conducted in adherence to the Declaration of Helsinki and the guidelines of Good Clinical Practice (GCP). We will recruit patients who meet the inclusion criteria and do not meet the exclusion criteria, to establish a cohort comprising 200 participants with cognitive impairment after robot-assisted neurosurgery treatment for ICH. Participants will sign a consent form and then be randomized into either the experimental or control group. The study design is shown in Fig 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEligibility criteria\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEligible patients are those who fulfill all of the following inclusion criteria and do not have any listed exclusion criteria.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eDiagnostic criteria\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e（1）Meet the diagnostic criteria for ICH according to \u0026ldquo;Chinese guidelines for diagnosis and treatment of acute intracerebral hemorrhage 2019\u0026rdquo;\u003csup\u003e[24]\u003c/sup\u003e;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e（2）Meet the diagnostic criteria for post-stroke cognitive impairment (PSCI) according to \u0026ldquo;European Stroke Organisation and European Academy of Neurology joint guidelines on post-stroke cognitive impairment\u0026rdquo;\u003csup\u003e[12]\u003c/sup\u003e;\u003c/p\u003e\n\u003cp\u003e（3）Meet the traditional Chinese medicine (TCM) diagnostic criteria for deficiency of the liver and kidney, phlegm and stagnant blood obstructing the meridians pattern.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eInclusion criteria\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e（1）Meet the diagnostic criteria of ICH and use robot-assisted neurosurgery to treat ICH;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e（2）Meet diagnostic criteria for PSCI;\u003c/p\u003e\n\u003cp\u003e（3）Meet diagnosis of deficiency of the liver and kidney, phlegm and stagnant blood obstructing the meridians pattern;\u003c/p\u003e\n\u003cp\u003e（4）Aged 18 and above;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e（5）Not limit gender;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e（6）2 weeks after robot-assisted neurosurgery;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e（7）The participants exhibit a clear consciousness, possess normal visual and auditory capabilities, and are capable of participating in neuropsychological evaluations;\u003c/p\u003e\n\u003cp\u003e（8）Submit informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eExclusion criteria\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(1)\u0026nbsp; \u0026nbsp;\u0026nbsp;Other types of dementia besides VaD, such as AD, dementia with Lewy bodies (DLB), and frontotemporal dementia;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(2)\u0026nbsp; \u0026nbsp;\u0026nbsp;Patients with other diseases that can affect cognitive function, such as Parkinson\u0026apos;s disease (PD), normal pressure hydrocephalus (iNPH), brain tumor, encephalitis, thyroid dysfunction, severe anemia, syphilis, and acquired immune deficiency syndrome(AIDS);\u003c/p\u003e\n\u003cp\u003e(3)\u0026nbsp; \u0026nbsp;\u0026nbsp;Patients experiencing severe visual or auditory impairments, apraxia, aphasia, or apparent neurological abnormalities, who are unable to cooperate with examinations;\u003c/p\u003e\n\u003cp\u003e(4) Patients with communication difficulties, patients with a history of mental disorders；\u003c/p\u003e\n\u003cp\u003e(5)\u0026nbsp; \u0026nbsp;\u0026nbsp;Patients with depression disorder, Hamilton Depression Scale ( HAMD ) \u0026ge; 17 points;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(6)\u0026nbsp; \u0026nbsp;\u0026nbsp;Patients diagnosed with alcohol or drug dependency within the past six months;\u003c/p\u003e\n\u003cp\u003e(7) \u0026nbsp; \u0026nbsp;Patients suffering from severe hepatic and renal dysfunction, heart failure or other serious primary diseases;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(8) \u0026nbsp; \u0026nbsp;Preconceptional, lactating, and pregnant women.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRandomization scheme\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this study, subjects will be enrolled in a centralized administration program. All subjects will be enrolled consecutively and randomized into the experimental or control groups (1:1). The randomization number and grouping will be conveyed to the sub-center principal investigator (PI) by the center PI at the time of patient enrollment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRobotic Surgery Operations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(1)\u0026nbsp; \u0026nbsp;\u0026nbsp;Preoperative localization: On the day of surgery, perform cranial Computed tomography (CT) at the Radiology Department after the insertion of five bone nails. Then plaster three or four MRAKs on the head surface to encircle the lesion. Ensure that three MRAKs are not collinear, and four MRAKs are not coplanar. Subsequently, the localized image data, including cranial Computed tomography angiography (CTA) with a 1 mm layer thickness, should be imported into a computer system.\u003c/p\u003e\n\u003cp\u003e(2)\u0026nbsp; \u0026nbsp;\u0026nbsp;Use computer surgical planning software to make an operative plan, outline the lesion, confirm surgical target and puncture paths, and display 3D images. Use a 3-pin head immobilization device to secure the patient\u0026apos;s head. Perform 3D structured light registration or markers registration. Check that the positioning accuracy is within 1 mm. Then, register the patient and the robotic arm. In succession, click on [Target Lock]-[Target Registration]-[Surgical Simulation]-[Robotic Arm Positioning]. Then, click the path of \u0026quot;Verify Target,\u0026quot; select [Target Lock]-[Target Registration]-[Surgical Simulation]-[Positioning], check the path arrival. The robotic arm automatically positions itself at the verification point. Check that the positioning accuracy is within 1 mm.\u003c/p\u003e\n\u003cp\u003e(3)\u0026nbsp; \u0026nbsp;\u0026nbsp;Anesthesia: The choice between local anesthesia and general anesthesia depends on the patient\u0026apos;s condition.\u003c/p\u003e\n\u003cp\u003e(4)\u0026nbsp; \u0026nbsp;\u0026nbsp;Disinfection and draping: The surgical area must be sterilized, after which sterile drapes should be draped. Place a sterile bag onto the robotic arm and install the sterile guider and adapter.\u003c/p\u003e\n\u003cp\u003e(5) \u0026nbsp; \u0026nbsp;Surgery: The incision for the surgery follows the path determined by robotic planning. The scalp is incised for approximately 3 centimeters before drilling into the skull. The puncture is executed along the robot\u0026apos;s predetermined path, and a drain is subsequently placed along the channel leading to the target location. The volume of aspirated hematoma amounts to 90% of the preoperative calculation. The drain is maneuvered beneath the skin for a distance of 2cm, then threaded through the skin and secured in place.\u003c/p\u003e\n\u003cp\u003e(6) \u0026nbsp; \u0026nbsp;After the surgery, the scalp is sutured in layers, sterilized, and bandaged again, and then patients are sent to the postoperative room.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIntervention\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe control group participants receive conventional treatment, while the experimental group participants receive conventional treatment combined with oral administration of FCYC (four capsules, three times a day) for a 12-week course of treatment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFollow-up and points of data capture\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe points of follow-up visits in the trial are as follows: 3 months \u0026plusmn; 7 days, 6 months \u0026plusmn; 14 days, and 12 months \u0026plusmn; 14 days after enrolment. The visits will be conducted by trained professionals at each center. These items will be documented during subsequent follow-up visits, including (1) the National Institutes of Health Stroke Scale (NIHSS), the modified Rankin scale (mRS), and perioperative Brain Function Assessment Scale; (2) follow-up events: all-cause death/vasogenic death/non-vasogenic death, recurrent stroke, myocardial infarction/heart failure, endovascular operation or surgery; (3) secondary prevention drug compliance; (4) management of blood pressure; (5) adverse events. In addition, Safety indicators, cranial MRI, blood proteomics, and TCM syndrome evaluation scale are performed at only the first follow-up and enrolment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcome measures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary efficacy outcome of this study is the change in test scores on the Perioperative Brain Function Assessment Scale after 12 weeks of treatment compared to baseline values. The Perioperative Brain Function Assessment Scale comprises several scales, including the Montreal Cognitive Assessment (MoCA), the Mini-Mental State Examination (MMSE), the Verbal Fluency Test (VFT), the Boston Naming Test-15 (BNT-15), the Chinese Auditory Learning Test (CAVLT), the Digital Span Test (DST), the Symbol Digit Modalities Test (SDMT), the Stroop Color-Word Test (Stroop-CWT), the Color Trails Test (CTT), the Rey Complex Figure Test(RCFT), HAMD, the Hamilton Anxiety Scale(HAMA), the Pittsburgh Sleep Quality Index(PSQI), and the Activities of daily living (ADL). The secondary efficacy endpoints include changes in test scores on the NIHSS, the mRS, and the TCM syndrome evaluation scale. Additional information includes demographics, blood pressure and blood lipid levels, MRI imaging features, and blood proteomics. Safety indexes consist of vital signs, laboratory examinations (blood routine, urine test, and hepatorenal assessment), electrocardiogram, and adverse events.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProcedures and variables\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter participants sign the consent form, the researchers register their basic information, demographics, medical history, and previous medication use. Subsequently, the patients undergo a series of medical tests, including blood pressure, electrocardiogram, blood and urine tests, MRI(3D T1 (mprage 1mm）+T2+FLAIR+DWI+SWI+MRA (3D TOF)), blood proteomics (ApoE、GFAP、NEFL、GDF15) and relevant scales. Relevant scales and data capture will be completed at each follow-up visit. Follow-up appointments are scheduled at the end of each visit. The schedule of procedures and variable collection for the trial is presented in Table 1.\u003c/p\u003e\n\u003cp\u003e\u003cimg 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\"\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSample size estimation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSample size estimation was based on the primary efficacy measures. Based on the results of the previous study, each group should have 80 participants, with a significance level of \u0026alpha; at 0.05 for a two-tailed test and a power (1-\u0026beta;) at 0.80. Considering a 20% drop-out rate, the final sample size is 100 cases in the test group and 100 cases in the control group, totaling 200 cases.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSAS software will be used for statistical analysis. All statistical analyses will be performed using two-sided tests or 95% confidence intervals at a 5% significance level. For quantitative data, t-test and one-way ANOVA will be used. Nonparametric data will be analyzed through the Mann-Whitney test, while categorical data will be evaluated using either the chi-squared test or the chi-squared test for trend. The study will evaluate primary efficacy indicators using analysis of covariance (ANCOVA). Survival analysis will be conducted using the Cox proportional-hazards model. Multivariate analysis will be performed using unconditional logistic regression. Correlation analysis will utilize the Spearman correlation test.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNumber of centers\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere are six participating organizations: Qinhuangdao Hospital of Traditional Chinese Medicine, Tsinghua University Yuquan Hospital, Kunming Sanbo Brain Hospital, Weifang Hospital of Traditional Chinese Medicine, Kaifeng Third People\u0026apos;s Hospital, Shandong Public Health Clinical Center.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics and mangement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData recording and management\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor each enrolled subject, a Case Report Form (CRF) will be completed and signed by the well-trained researchers. This also applies to records for patients who fail to complete the study. If a participant withdraws from the study, the reason must be noted on the CRF. All study-related files, including consent forms, the CRF, questionnaires, medical records, and other records, will be stored in a locked space or on a password-protected computer in each hospital for three years after the study is completed. Researchers must adhere to professional confidentiality rules and maintain the confidentiality of all personal identity and medical information about their patients. A designated person is responsible for managing the original research materials. Independent clinical research associates (CRA) will regularly audit and monitor the study at each hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSafety and adverse events\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this study, adverse reactions may occur in individuals taking the oral medication FCYC. Adverse reactions are primarily concentrated in the digestive system, with symptoms such as nausea, emesis, abdominal pain, diarrhea, epigastric distension, and decreased appetite. Other systemic symptoms may encompass palpitation and skin pruritus, etc. These adverse reactions are generally mild and can be alleviated by discontinuing the use of FCYC. Adverse events must be recorded on the CRF as they occur. Each event should be described in detail, including start and end dates, severity, relationship to the therapy as judged by the investigator, action taken, and outcome. Reporting serious adverse events and unanticipated problems to the ethics board, competent authorities, sponsors, and drug regulatory agencies is required on time. The principal investigator should perform periodic cumulative reviews of all adverse events and hold investigator meetings as necessary to assess the risks and benefits of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical considerations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study has been approved by the ethics committee of Qinhuangdao Hospital, Dongfang Hospital Beijing University of Chinese Medicine (Ethics approval number: 202311A), and has been registered at Clinicaltrials.gov with the identifier: NCT06673602. The investigator is responsible for fully informing subjects or their legal representatives about the purpose, procedures, and potential risks of the study, as well as providing information on alternative treatments. Subjects have the right to withdraw from the study at any time. Ensure that subjects are fully informed, have sufficient time to consider and voluntarily choose to consent to participation in the study. Avoid any inappropriate inducement of subjects. Before the study commences, participants will sign a written informed consent. The privacy and data of the subjects will be safeguarded throughout the study.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eICH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIntracerebral hemorrhage\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFCYC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFufang Congrong Yizhi Capsules\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCRF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCase Report Form\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eVaD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eVascular dementia\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eVCI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eVascular cognitive impairment\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAlzheimer's disease\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMRI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMagnetic Resonance Imaging\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eGCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eGood Clinical Practice\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePSCI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePost-stroke cognitive impairment\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTCM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTraditional Chinese medicine\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDLB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDementia with Lewy bodies\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eParkinson's disease\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eiNPH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNormal pressure hydrocephalus\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAIDS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAcquired immune deficiency syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHAMD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHamilton Depression Scale\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePrincipal investigator\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComputed tomography\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCTA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComputed tomography angiography\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNIHSS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNational Institutes of Health Stroke Scale\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003emRS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eModified Rankin scale\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMoCA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMontreal Cognitive Assessment\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMMSE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMini-Mental State Examination\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eVFT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eVerbal Fluency Test\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eBNT-15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eBoston Naming Test-15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCAVLT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eChinese Auditory Learning Test\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDST\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDigital Span Test\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSDMT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSymbol Digit Modalities Test\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eStroop-CWT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eStroop Color-Word Test\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCTT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eColor Trails Test\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRCFT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRey Complex Figure Test\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePSQI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePittsburgh Sleep Quality Index\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eADL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eActivities of daily living\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCRA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eClinical research associates\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the participants for their involvement.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eQZ design the trial and participate in all phases of the study. WW assists with management. Patients are enrolled and observed in subcenters by WW, ML, JZ, SW, JR, and MZ. Data analysis and statistics by MM. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is funded by CHNI Traditional Chinese Medicine Development Center(ZW2023A005) and Lei Yun Shang Pharmaceutical Group Co., Ltd.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the local ethics committee of the Qinhuangdao Hospital, Dongfang Hospital Beijing University of Chinese Medicine (Ethics approval number: 202311A).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConsent for publication has been obtained from Qinhuangdao Hospital, Dongfang Hospital Beijing University of Chinese Medicine.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there is no conflict of interest regarding the publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eDepartment of Neurology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China. \u003csup\u003e2\u003c/sup\u003eDepartment of Neurology, Qinhuangdao Hospital, Dongfang Hospital Beijing University of Chinese Medicine, Qinhuangdao, Hebei, China. \u003csup\u003e3\u003c/sup\u003eThe Faculty of Medicine, Qilu Institute of Technology, Jinan, Shandong, China. \u003csup\u003e4\u003c/sup\u003eDepartment of Anesthesiology, Weifang Hospital of Traditional Chinese Medicine, Weifang, Shandong, China. \u003csup\u003e5\u003c/sup\u003eDepartment of Neurosurgery, Kaifeng Third People\u0026apos;s Hospital, Kaifeng, Henan, China. \u003csup\u003e6\u003c/sup\u003eDepartment of Neurosurgery, Kunming Sanbo Brain Hospital, Kunming, Yunnan, China. \u003csup\u003e7\u003c/sup\u003eDepartment of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, China. \u003csup\u003e8\u003c/sup\u003eDepartment of Neurosurgery, Tsinghua University Yuquan Hospital, Beijing, China.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAn SJ, Kim TJ, Yoon BW. Epidemiology, Risk Factors, and Clinical Features of Intracerebral Hemorrhage: An Update. J Stroke. 2017;19(1):3-10. doi: 10.5853/jos.2016.00864.\u003c/li\u003e\n\u003cli\u003eWriting Group Members; Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, Das SR, de Ferranti S, Despr\u0026eacute;s JP, Fullerton HJ, Howard VJ, Huffman MD, Isasi CR, Jim\u0026eacute;nez MC, Judd SE, Kissela BM, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Magid DJ, McGuire DK, Mohler ER 3rd, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Rosamond W, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Woo D, Yeh RW, Turner MB; American Heart Association Statistics Committee; Stroke Statistics Subcommittee. Executive Summary: Heart Disease and Stroke Statistics--2016 Update: A Report From the American Heart Association. Circulation. 2016;133(4):447-54. doi: 10.1161/CIR.0000000000000366.\u003c/li\u003e\n\u003cli\u003eGBD 2019 Stroke Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol. 2021;20(10):795-820. doi: 10.1016/S1474-4422(21)00252-0.\u003c/li\u003e\n\u003cli\u003eZhang X, Li H, Wang H, Zhang Q, Deng X, Zhang S, Wang L, Guo C, Zhao F, Yin Y, Zhou T, Zhong J, Feng H, Chen W, Zhang J, Feng H, Hu R. Iron/ROS/Itga3 mediated accelerated depletion of hippocampal neural stem cell pool contributes to cognitive impairment after hemorrhagic stroke. Redox Biol. 2024;71:103086. doi: 10.1016/j.redox.2024.103086.\u003c/li\u003e\n\u003cli\u003eFernando SM, Qureshi D, Talarico R, Tanuseputro P, Dowlatshahi D, Sood MM, Smith EE, Hill MD, McCredie VA, Scales DC, English SW, Rochwerg B, Kyeremanteng K. 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Long-Term Cognitive Decline After Stroke: An Individual Participant Data Meta-Analysis. Stroke. 2022;53(4):1318-1327. doi: 10.1161/STROKEAHA.121.035796.\u003c/li\u003e\n\u003cli\u003eZietemann V, Georgakis MK, Dondaine T, M\u0026uuml;ller C, Mendyk AM, Kopczak A, H\u0026eacute;non H, Bombois S, Wollenweber FA, Bordet R, Dichgans M. Early MoCA predicts long-term cognitive and functional outcome and mortality after stroke. Neurology. 2018;91(20):e1838-e1850. doi: 10.1212/WNL.0000000000006506.\u003c/li\u003e\n\u003cli\u003eHill G, Regan S, Francis R; Stroke Priority Setting Partnership Steering Group. Research priorities to improve stroke outcomes. Lancet Neurol. 2022;21(4):312-313. doi: 10.1016/S1474-4422(22)00044-8.\u003c/li\u003e\n\u003cli\u003eBiffi A, Bailey D, Anderson CD, Ayres AM, Gurol EM, Greenberg SM, Rosand J, Viswanathan A. Risk Factors Associated With Early vs Delayed Dementia After Intracerebral Hemorrhage. JAMA Neurol. 2016;73(8):969-76. doi: 10.1001/jamaneurol.2016.0955.\u003c/li\u003e\n\u003cli\u003eMoulin S, Labreuche J, Bombois S, Rossi C, Boulouis G, H\u0026eacute;non H, Duhamel A, Leys D, Cordonnier C. Dementia risk after spontaneous intracerebral haemorrhage: a prospective cohort study. Lancet Neurol. 2016;15(8):820-829. doi: 10.1016/S1474-4422(16)00130-7.\u003c/li\u003e\n\u003cli\u003eLiang X, Jin XL, Peng DT, Guo RJ, Liao X, Zhang YL. Expert consensus on clinical application of Compound Congrong Yizhi Capsules in treatment of vascular dementia. Zhongguo Zhong Yao Za Zhi. 2022;47(23):6514-6519. Chinese. doi: 10.19540/j.cnki.cjcmm.20221008.501.\u003c/li\u003e\n\u003cli\u003eHAN Qin, Xu Xiaoyu, GENG Yifei, Llu jingjing, Sun Xiaobo, Luo Yun. Mechanism of Fufang Congrong Yizhi Capsules in treatment of mild cognitive impairment based on network pharmacology. Chinese Pharmacological Bulletin. 2024; 40(02):334-343. doi: 10.12360/CPB202211034.\u003c/li\u003e\n\u003cli\u003eLi Mengyuan, Sun jinping, Sun Wei, Zhang Zhanjun, Li He. Clinical study of Compound Congrong Yizhi Capsule in treating mild to moderate Alzheimer\u0026prime;s disease. Journal of Beijing University of Traditional Chinese Medicine. 2024;47(08):1145-1151. doi: 10.3969/i.issn.1006 2157.2024.08.017.\u003c/li\u003e\n\u003cli\u003eYefei Wang, Ningqun Wang, Zhenmin Xu, Shaojiao Liu, Xiao Liang, Yunling Zhang, Xianglan Jin. Clinical efficacy and safety of compound Congrong Yizhi Capsules on Alzheimer\u0026apos;s disease in mainland China: A systematic review with trial sequential analysis and GRADE assessment. Ethnopharmacol. 2023;12:309:116208. doi: 10.1016/j.jep.2023.116208.\u003c/li\u003e\n\u003cli\u003eChinese Society of Neurology, Chinese Stroke Society. Chinese guidelines for diagnosis and treatment of acute intracerebral hemorrhage 2019. Chinese Journal of Neurology. 2019;52(12):994-1005. doi: 10.3760/cma.j.issn.1006-7876.2019.12.003.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Clinical Research Protocol, Cognitive impairment, Intracerebral hemorrhage, Fufang Congrong Yizhi Capsules, Robot-assisted neurosurgery","lastPublishedDoi":"10.21203/rs.3.rs-5901671/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5901671/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e \u0026nbsp;Intracerebral hemorrhage (ICH) is associated with high mortality and disability rates, which places a significant social burden. Robot-assisted neurosurgery with precise positioning and high stability has become an important advance in the development of minimally invasive surgery for ICH. Cognitive impairment is a common complication in patients with ICH, which seriously affects the stroke rehabilitation process. We are not sure about the medication treatment for cognitive impairment after robot-assisted neurosurgery treatment for ICH. In this CONPAIR trial, we will evaluate the safety and efficacy of Fufang Congrong Yizhi Capsules (FCYC) for cognitive impairment after robot-assisted neurosurgery treatment for ICH.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods and analysis \u003c/strong\u003eIn this multicentrer,\u003cstrong\u003e \u003c/strong\u003erandomized, controlled trial involving patients with cognitive impairment after robot-assisted neurosurgery treatment for ICH, we assessed medical management. Two hundred patients will be randomly assigned, in a 1:1 ratio, to either an experimental group or a control group. The experimental group will receive conventional treatment and oral administration of FCYC for 12 weeks or the control group will receive only conventional treatment. The primary safety end point was death within 30 days after enrollment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics and management \u003c/strong\u003eThe Case Report Form (CRF) will be completed and signed by well-trained researchers. We will monitor and promptly report adverse events throughout the trial. The privacy and data of the subjects will be safeguarded. Research Ethics Board approval has been obtained.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinicalTrials.gov number \u003c/strong\u003eNCT06673602\u003c/p\u003e","manuscriptTitle":"Evaluation on Fufang Congrong Yizhi Capsules (FCYC) of cognitive impairment after robot-assisted neurosurgery treatment for intracerebral hemorrhage (CONPAIR) : study protocol for a randomized controlled trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-04 08:48:05","doi":"10.21203/rs.3.rs-5901671/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ed04fc26-8125-4873-bffd-7d5af5e984e4","owner":[],"postedDate":"February 4th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-02-04T08:48:05+00:00","versionOfRecord":[],"versionCreatedAt":"2025-02-04 08:48:05","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5901671","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5901671","identity":"rs-5901671","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}