SurgeRy and physiothErapy Versus physIotherapy only for chronic paTellofemorAL paIn: study protocol for a randomiSed controllEd trial (REVITALISE)

SurgeRy and physiothErapy Versus physIotherapy only for chronic paTellofemorAL paIn: study protocol for a randomiSed controllEd trial (REVITALISE) | 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 Study protocol SurgeRy and physiothErapy Versus physIotherapy only for chronic paTellofemorAL paIn: study protocol for a randomiSed controllEd trial (REVITALISE) Myrthe P.F. van de Ven, Martin Ophey, Victor van de Graaf, Sebastiaan A.W. van de Groes, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4252434/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 15 Jan, 2025 Read the published version in BMC Musculoskeletal Disorders → Version 1 posted 9 You are reading this latest preprint version Abstract Background: Patellofemoral pain (PFP) is a common musculoskeletal disorder resulting in anterior knee pain. Physiotherapy is the current standard treatment, while surgical intervention (tibial tubercle transfer [TTT]) is reserved for chronic cases when nonoperative treatment has failed. However, to date, no randomized controlled trials (RCT) have compared TTT combined with a physiotherapy (PT) program PT to PT alone as the initial treatment for PFP. Methods: A single-centre RCT in patients with chronic PFP (>1 year) will be randomized to either TTT followed by PT (n=20) or to PT alone (n=20). The primary outcome is knee pain at 18 weeks for the TTT group and at 12 weeks for the PT group, measured by the visual analog scale (VAS). Secondary outcomes include Patient Recorded Outcome Measures (PROMs) using the Kujala score, International Knee Documentation Committee (IKDC) ‘Subjective Knee Form’, Tegner Activity score and EuroQol 5D-5L for quality of life. Range of motion (ROM) is measured using the decline step-down test (DSDT). The difference in direct medical costs will also be assessed. Discussion: The REVITALISE study is the first randomized study to compare surgical intervention (TTT) followed by PT to PT alone in patients with chronic PFP. This study will generate level-1 evidence on the most effective treatment for chronic PFP, which can be integrated into the national guideline to aid orthopaedic surgeons and physiotherapists in their decision-making and ultimately improve our care for patients with chronic PFP. Trial registration Study Identifier NCT06227806, registered on 26 Jan 2024 on ClinicalTrials.gov. The study underwent independent peer review and received approval from the ethical review board (number NL80956.091.22). Patellofemoral pain tibial tubercle transfer physiotherapy randomized controlled trial Figures Figure 1 Introduction Background and rationale Patellofemoral pain (PFP) is one of the most common forms of anterior knee pain, with a reported prevalence of 15% to 45% in physically active adolescents and adults, and it is more commonly diagnosed in women (1-3). The symptoms are aggravated by activities involving loading the patellofemoral joint during weight bearing on a flexed knee (4). A relatively large proportion of patients (40%) diagnosed with PFP continue to experience symptoms one to six years after diagnosis (5-8). The treatment goals for PFP are to reduce pain, improve patellofemoral tracking and alignment, and return to the preinjury level of activities. The conservative treatment of PFP with physiotherapy for the quadriceps and hip muscles as the cornerstone has shown varying degrees of success, from no difference (9, 10) to improvement (7, 11, 12). To date, surgical intervention is not recommended in the international PFP consensus statement because high-level evidence about its effects is lacking (7). In the Dutch guideline on ‘anterior knee pain’, a multidisciplinary stepped care treatment strategy model is incorporated, consisting of education and an exercise program (13). However, if symptoms persist after 12 weeks, the effect of further exercise therapy or surgery is unknown. Carlson et al. (14) reported that the tibial tubercle-trochlear groove (TT-TG) distance was significantly greater in patients with PFP. In patients with patellar dislocation, a TT-TG >15 mm is considered a clinically relevant anatomical substrate that negatively affects patellofemoral tracking and stability (14, 15). According to a recent meta-analysis, tibial tubercle transfer (TTT) can lead to good results with clinically meaningful improvement in patients with patellofemoral maltracking without instability (16). It is considered a relatively safe procedure with a low complication rate (17, 18). However, no randomized controlled trials (RCT) analysing the value of TTT or comparing TTT with physiotherapy for the treatment of chronic PFP have been published. To further clarify the additional value of surgery in PFP, a RCT will be conducted to compare TTT in conjunction with a physiotherapy (PT) program versus a PT alone in patients with chronic PFP and a TT-TG > 15 mm. Objectives The primary objective of this study is to compare the between-group difference in knee pain over time for TTT followed by PT versus PT alone in patients aged 18-35 years with chronic PFP. We hypothesize that TTT combined with PT will result in a larger decrease in knee pain than PT alone. Secondary objectives are to compare the between-group difference in change in 1) knee function, measured by validated Patient Recorded Outcome Measures (PROMs), 2) range of motion (ROM), 3) quality of life (QoL), 4) the functional limitations, and 5) the direct medical costs. The results of this study can be used to develop and implement a better stepped care treatment strategy for PFP and can be integrated in the national guideline for “anterior knee pain” (13). Methods Study design and setting A single-centre RCT. All patients will be recruited and included at the Orthopaedics Department of the Canisius Wilhelmina Hospital (CWZ), Nijmegen, the Netherlands. Eligible patients are randomized into two equal groups: The TTT group: 20 PFP patients who will be treated with TTT at the hospital of randomisation, followed by a 12-week supervised PT protocol; The PT group: 20 PFP patients who will be treated with the same 12-week supervised PT protocol. This study will be conducted according to the principles of the Declaration of Helsinki (19) and in accordance with the Medical Research Involving Human Subjects Act (WMO), Good Clinical Practice (GCP) and the General Data Protection Regulation. The study will also be carried out in accordance with local legal requirements. This study was approved by the independent Ethical Committee METC Oost-Nederland (protocol number NL80956.091.22) and was registered on ClinicalTrials.gov (study identifier NCT06227806). Written informed consent will be provided by each participant before the start of the study assessments or the intervention. This protocol adheres to the SPIRIT checklist items. Participants Participants between 18 and 35 years of age with at least 12 months of PFP and a tibial tubercle trochlear groove (TT-TG) distance ≥15 mm on CT or MRI will be recruited at the CWZ hospital in Nijmegen, The Netherlands. PFP is defined as: Pain around or behind the patella aggravated by at least one activity that loads the patellofemoral joint (e.g., squatting, running, or jumping); Pain during daily life activities, such as: standing for an extended period, walking, or walking upstairs or downstairs. Participants will be excluded when one or more of the following exclusion criteria are met: Previous knee surgery; Reported ligamentous or meniscal injuries of the knee; A history of patellar dislocation; however, subjects with patellar subluxation are included in the study; Malrotational deformity of the lower extremity evident from physical examination; Disabling general illness; Other diagnosed knee injuries, either clinically (such as jumper's knee) or radiologically (such as osteochondritis dissecans); Patients who cannot undergo surgery; Pregnancy; Patients with inability to complete follow-up or with limited understanding of the Dutch language. Patient recruitment All eligible patients will be approached by their treating physician at the orthopaedic department of the CWZ, provided with adequate patient information, and handed out a patient information file (PIF). They will be instructed about the TTT, PT, and possibility to crossover after 12 weeks of the PT. After having had sufficient time (>24 h) to reconsider participation, they will be contacted by a researcher to obtain approval and plan a baseline visit where participants will sign informed consent. Patients will also be asked for permission to approach them for future related research. A list of all eligible patients will be recorded in a screening log, including those that do not wish to participate, as well as the reason if provided. Randomisation Patients will be enrolled in the study by the study coordinator in the orthopaedic department. All patients who consent to participate in the study and meet the inclusion criteria will be randomized. Patients will be randomised to the TTT + PT: PT only in a 1:1 ratio. The randomisation process will be carried out using a computer-generated randomisation method in the Castor electronic data capture (EDC) system (20), in random blocks of 4. The exact randomisation algorithm is unknown to any of the investigators; hence, concealment of allocation is successful in all patients. Blinding Neither the treatment providers nor the study coordinator will be blinded due to the study design (with a blatant intervention). Interventions Tibial Tubercle Transfer (TTT) The TTT is a surgical procedure that realigns the patella and, as a result, improves patellar tracking in the trochlear groove. TTT is a relatively safe procedure with a low complication rate (<1% for all major complications) (17, 18). The TTT will be scheduled as soon as possible after randomisation, with a target of <2 weeks. All surgeries will be carried out by either SK or Dr. S. Tigchelaar, both of whom have extensive experience in treating patellofemoral knee disorders. The operative technique used is described previously (21). Patients will be discharged the same day after surgery. Then, a splint phase is started for 4-6 weeks. The physiotherapist will be instructed to contact the study coordinator when the PT begins (see below). After 6 weeks, an outpatient visit with the orthopaedic surgeon is scheduled for a check-up following regular care. At 6 months, there will be an outpatient visit following regular care for evaluation of possible symptoms caused by the hardware. Consequently, removal of hardware (ROH) can be performed if the patient experiences pain derived from the hardware and if complete bone healing is observed on radiographs. Physiotherapy (PT) program This will start as soon as possible in the PT group and after the splint phase in the TTT group. The PT will consist of three levels and will be supervised by a physiotherapist. According to predefined criteria, the physiotherapist decides whether a patient can step onto the next level within the PT. The PT consists of flexibility, neuromuscular coordination, and strength exercises for the quadriceps and hip muscles. The PT is developed by a team of experienced physiotherapists who are specialized in treating patients with PFP and based upon the most recent physiotherapeutic insights (7). In addition to training, education about PFP is incorporated into the PT according to the most recent insights regarding pain mechanisms (22, 23). Physiotherapists who participate as self-chosen treating health care professionals by patients will be requested to follow the instructional video developed by the REVITALISE study team. Additionally, the three levels of exercise of the PT program are available on the Physitrack® tool for both participating physiotherapists and patients with PFP to improve exercise adherence and support clinical decision-making. In total, there will be 12 sessions with the physiotherapist. In the first three weeks of the PT, patients visit the physiotherapist twice a week. This will occur once a week from week 3 to week 6. This will occur every other week from week 6 to week 12. However, the treating physiotherapist may increase or decrease the number of appointments if needed. The PT is included in the Supplementary file, which contains more detailed information and instructions. TTT and PT versus PT only The study involves four outpatient visits (at inclusion/randomisation, 6 weeks after the start of the intervention, after 12 (PT group)/18 weeks (surgery + PT group), and after 26 weeks in both groups). A physical examination will take place at every outpatient visit, with the addition of the decline step-down test (DSDT) at baseline and 12/18 weeks after randomisation. Patients will complete online questionnaires at every outpatient visit and 12 months after randomisation. After randomisation, patients will either have a TTT (treatment group) or start with the PT (control group) . From 12 weeks, there will be the possibility to crossover from the PT group to surgery if the symptoms do not improve. Surgery will then be performed within 2 weeks . Participants will then follow the same protocol as the TTT group, including the PT program, surveys, and physical measurements. Criteria for discontinuing or modifying allocated interventions Subjects can leave the study at any time for any reason if they wish to do so without any consequences. The investigator can decide to withdraw a subject from the study for urgent medical reasons. There will be no follow-up of patients who withdraw from the study, but reasons for withdrawal will be recorded. Patients who withdraw from the study will not be replaced. Strategies to improve adherence to interventions To improve adherence, patients will receive the PT in text and with visual instructions on the Physitrack app if possible. They will also receive a weekly questionnaire to register the amount of exercising with the physiotherapist and at home, as well as their VAS score during the 12-week PT. Relevant concomitant care permitted or prohibited during the trial Patients are permitted to take any medication such as paracetamol or other prescribed pain killers. The use of other interventions, such as braces or insoles, is not restricted. Provisions for post-trial care Post-trial care will follow standard care, especially for the surgery group. Therefore, we do not expect post-trial harm from participation in this study. There are no specific provisions for post-trial care. Outcomes Primary outcome The main study parameter will be the between-group difference in activity-related knee pain at 10-12 weeks after PT in both groups (week 16-18 in TTT group, week 10-12 in PT group), measured with the 10cm VAS-scale. In this period, an expected plateau phase of pain will be reached. The mean from the three scores (week 10, 11, and 12) will be used to account for variance in pain levels. Participants will assess the maximum pain they had felt during the previous 7 days when participating in activities of daily living such as ascending stairs, descending stairs and standing up from a sitting position. The 10-cm VAS is a valid and responsive tool for evaluating overall pain in patients with PFP (24). A minimal clinically important difference (MCID) of 2 cm or 20% has been reported to reflect real changes in a patient’s symptoms (24). Secondary outcomes Secondary outcomes are between-group difference in: pain during the intervention (VAS); functional outcomes (Kujala score, IKDC), activity level (Tegner score), quality of life (EQ-5D-5L), and functional ROM (DSDT) at 12/18 weeks follow-up, as well as the change over time from baseline to 12 months follow-up. Furthermore, this study will provide a global overview of the direct medical costs of surgery + PT compared to PT only treatment. VAS Difference in participants’ assessment of pain during the intervention (TTT + PT or PT only) is measured by the VAS pain score in the weekly questionnaires during the PT, and at 6 and 12 months follow-up. Functional outcomes The Kujala score is a 13-item questionnaire used to evaluate subjective symptoms and functional limitations in patients with PFP (25). Kujala grade ranges from 0-100, with 100 reflecting no signs of PFP. This index shows high validity and is responsive to change (24). To detect improvement, a change of 8-10 points is required (24). The International Knee Documentation Committee (IKDC) ‘Subjective Knee Form’ is a tool containing 11 items: 7 on knee symptoms, 2 on function, and 2 on sports activities, resulting in a score ranging from 0-100, with 100 reflecting the highest level of pain and functional restrictions. The IKDC showed high internal consistency (0.92) and test-retest reliability (0.95), with a value change of 9 points indicating true change (26). Activity level The Tegner activity score consists of 1 item, which scores the level of work- and sport activities on a 10-point scale, with 10 reflecting a high level of activity (27). Quality of life The health-related quality of life (EQ-5D-5L) questionnaire consists of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that are scored on 5 levels (no problems, slight problems, moderate problems, severe problems, and extreme problems) (28). An index value will be calculated to reflect health status on a scale of 0 to 1, where 1 represents maximum quality of life. Functional ROM The maximum pain-free flexion angle (MPFFA) is measured by the DSDT. The DSDT is a reliable and valid performance test simulating stair descent with almost perfect intra- and interobserver reliability ( ICC 0.83-0.85) and an average positive correlation between the DSDT score and the total AKPS score ( r s = 0.31, p = .030) (29). Other study parameters This study will include items strongly recommended by the International Patellofemoral Research Network (iPFRN) in the REPORT-PFP consensus statement (30). These include demographics, such as age, biological sex, symptom duration, and unilateral/bilateral symptoms (30). Furthermore, physical examination data, such as height and weight (and hence BMI) will be recorded. To evaluate the adherence to the PT, patients will also receive a weekly email during the PT asking how often they have visited the physiotherapist and how often they have executed the PT at home. Any adverse events (AEs) will be monitored, as explained in the ‘Adverse event reporting and harms’ section. The rate of ROH after surgery will be registered as a separate outcome. Participant timeline Figure 1 provides an overview of the study design and procedures. Sample size Our primary outcome is the between-group difference in overall knee pain 12 weeks after PT and 18 weeks after TTT and PT, measured with the VAS score. Our hypothesis is that the improvement in the TTT group will be greater than the improvement in the PT group. To detect the superiority of the treat-to-target TTT with PT to PT alone, we calculated the required sample size for an independent samples t-test on the following assumptions: power (1-beta) 0.8, significance level (alpha) 0.05, two-sided testing, MCID mean VAS-pain in TTT + PT: mean 4.1, standard deviation (SD) 2.0, versus PT alone: mean 6.1, and SD 1.9. The SD was based on a study by Bayoumi et al., which compared different surgical techniques for patellar maltracking without instability (16). The MCID was based on a study by Crossley et al., who demonstrated that a change in the VAS score of two points or more is considered clinically relevant and worthwhile for performing surgery (24). Based on these parameters, a sample size of 16 patients per group is needed. Anticipating on a loss to follow-up of 20%, 20 patients per group are needed. Feasibility of recruitment Given the >50 TTTs for patients with chronic PFP already performed annually in the CWZ, and accounting for patients who are not willing to participate, we expect to have sufficient numbers of patients for our inclusion within 12 months. The CWZ is a nationally recognized top clinical expertise centre in (patellofemoral) knee surgery and performs approximately 80% of patellofemoral surgeries in the Netherlands, including TTT (31). Data collection methods Plans for assessment and collection of outcomes The clinical assessment data and PROMs data will be collected in CastorEDC. This data collection will be organized by the study coordinator. Plans to promote participant retention and complete follow-up Participants will be closely monitored by the study coordinator to ensure follow-up. To reduce patient burden, data collection will be web-based as often as possible. Data management We have created a data management plan in line with the General Data Protection Regulation, which can be viewed upon request. The data will be managed within the online CastorEDC system. This is a secure cloud-based platform that contains an audit trail, automatic range checks, and pseudomized study IDs for all data. Confidentiality The type of data that is collected is in line with the General Data Protection Regulation. Study IDs are pseudonymized in CastorEDC for all data. The key to the study ID is safely kept by the study coordinator. The data will be stored for 15 years. Statistical methods for primary and secondary outcomes In accordance with the international patellofemoral research network, the REPORT-PFP consensus statement outcome measure description will be adequate (30). The items described in the assessment will be in adequate detail to allow replication. We will report n (%), the mean (SD), and median (interquartile range; IQR) for categorical/descriptive, normally distributed continuous and non-normally distributed continuous data, respectively (30). Results over time will be visualized descriptively in spaghetti plots. The primary analyses will be performed following the intention-to-treat method. Statistical analyses will be done using R software (R Foundation for Statistical Computing, Vienna, Austria). Primary endpoint The primary outcome parameter is the between-group difference in VAS score, at 10-12 weeks after start of the PT (week 16-18 for TTT group). For analysis of the primary parameter, the mean of the three VAS scores at 10, 11, and 12 weeks of the PT in the TTT group will be compared with that of the PT group. Baseline VAS score, biological sex, and treatment group will be included as covariates in a multivariable linear regression analysis. Secondary endpoints For the secondary parameters (functional outcomes on the Kujala and IKDC score, activity level on Tegner score, QoL on the EuroQol-5D-5L score, and functional ROM on the DSDT score) at 12 weeks after the start of the PT (week 18 for TTT group), the between-group difference will be assessed using multivariable linear regression analysis in the same manner as the primary endpoint. To assess the longitudinal clinical effectiveness of both groups, linear mixed models for repeated measures (MMRM) will be used for the secondary outcomes and activity-related knee pain on VAS score during the PT from baseline to 12 months follow-up. MMRMs take the correlation of multiple measurements over time within one patient into account. In the MMRM, this secondary outcomes will be analysed as dependent variables. To evaluate the effect at different time points, the fixed effects will be patient, time, and the treatment group (TTT versus PT only). Time will be included as dummy variable, with baseline as reference. The main effects for treatment will be reported as difference in means with 95% confidence intervals (CI). Other study parameters The economic aspect will be published based upon an estimation of the direct medical healthcare costs for TTT + PT and conservative care for PFP + PT, including costs for hospital visits, scans, surgery, physiotherapy, prescription medication, and possible readmission. The medical costs are based on resource costs. Furthermore, ROH and complications will be reported. Methods for additional analyses (e.g. subgroup analyses) Per-protocol analyses will be performed including only the patients that did not crossover from the PT to TTT group, for comparison with intention-to treat analysis. Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data In the case of missing outcome values, data will be imputed before analysis using multiple imputation methods. Plans to provide access to the full protocol, participant-level data and statistical code The trial protocol is available from the corresponding author upon reasonable request. Data will be handled according to the FAIR principles (a guideline to improve the Findability, Accessibility, Interoperability, and Reusability of Digital Assets) (32). After completion of the study, metadata will be available upon request. For access to anonymised participant-level data and statistical code, an application can be submitted to the corresponding author. Monitoring Data monitoring A data monitoring plan has been created and is available upon request. As both groups in this study are within the spectrum of regular care, no data safety monitoring board is installed. Furthermore, since this is a monocentre study, a coordinating centre and trial steering committee are not needed. No interim analyses will be performed. As the treatments in both groups are within the range of usual care, we do not anticipate differences between the groups that could warrant early cessation of the study due to detrimental effects to the participant. Adverse event reporting and harms All AEs reported spontaneously by the subject or observed by the investigator or his staff will be recorded. The patient's general practitioner will receive a letter about the patient's participation in the study. To prevent underregistration of AEs, we will ask for this information during outpatient visits. AEs will be reported until 12 weeks for the PT group and 18 weeks for the surgery group. Elective hospital admission will not be considered a serious adverse event (SAE). Prolongation of initial hospital stay after surgery due to pain or reduced mobility and the need for mobilization under sedation (hardly ever performed after TTT) will not be considered a serious adverse event. The investigator will report all SAEs to the sponsor without any delay after obtaining knowledge of the events. The sponsor will report the SAEs through the web portal ToetsingOnline to the accredited METC, which approved the protocol within 7 days of first knowledge for SAEs that result in death or are life threatening, followed by a period of a maximum of 8 days to complete the initial preliminary report. All other SAEs will be reported within a maximum of 15 days after the sponsor has first knowledge of the serious adverse events. SAEs will be reported until 12 weeks for the PT group and 18 weeks for the surgery group. Auditing Monitoring will be performed once per year. It will involve monitoring the investigator site file, informed consent, SAEs, in- and exclusion criteria, among others. Monitoring will be performed according to Nederlandse Federatie van Universitair Medische Centra (NFU) guidelines and a monitoring plan by a monitor from the CWZ academy. Protocol amendments All amendments will be reported to the ethical review committee that gave a favourable opinion. Non-substantial amendments will not be notified to the accredited ethical review committee or the competent authority but will be recorded and filed by the investigator. Dissemination plans Overall trial results will be communicated to participants, presented at (inter)national conferences, and reported in peer-reviewed journals. There are no publication restrictions. Medically relevant incidental findings will be shared with the study subject. Discussion The REVITALISE study is the first RCT to compare surgical intervention followed by PT to PT alone in patients with chronic PFP. This study’s results will gain insight into the most effective treatment for patients with chronic PFP and will enhance our treatment of this high burden disease with currently a high variability of provided care (13). This variation seems to be not or weakly associated with patient characteristics, elucidating the need for a more standardized approach to prevent over- or under treatment. The study will answer the question whether patients receiving TTT followed by PT have less pain and better functional outcomes than those receiving PT alone. In addition to measuring the effectiveness of TTT plus PT versus PT alone, a range of other outcomes will be assessed (e.g., physical function, complications, direct medical costs), to provide a broader view of the effect of both treatments. The strengths of the study include the randomized controlled design supported with multiple involved professions. Physiotherapists are involved in the design of the PT. Orthopaedic surgeons are involved in the TTT protocol. Since this is a single-centre study, little or no variation in surgical technique is expected. This study has several limitations. First, the crossover design potentially affects long-term (i.e., >12 weeks) comparisons of the groups, as well as induces bias in cases where patients become less motivated to follow physiotherapy. However, as the primary analysis is according to the intention-to-treat principles, we do not expect this to have a major impact. Second, at the time of presentation at the hospitals, patients will have had different treatments, i.e., the care given by the family physician, the outpatient physiotherapist, or other involved professionals. In our physiotherapy program, special care is given to education of the patient about PFP, as well as a focus on building balance and strength in multiple muscle groups, not only the quadriceps. Third, for logistical reasons, it is not possible for all participants to receive physiotherapy from the same physiotherapist. To limit protocol variations, we will contact each physiotherapist to explain the research design, the PT, and the need to adhere to this program. Simultaneously, the physiotherapist should tailor the program to the participants, as their individual needs and limitations are always the highest priority. The results of this study will address an important evidence gap and will have a significant impact on the care of patients with chronic PFP. TRIAL STATUS The study is currently open for inclusion. Recruitment started on 24 October 2023, and the expected end date of recruitment is 24 October 2024. Abbreviations AE: Adverse event; AKPS: Anterior Knee Pain Score (Kujala score); BMI: Body Mass Index; CI: Confidence Interval; CT: Computer Tomography (scan); CWZ: Canisius Wilhelmina Ziekenhuis; DSDT: Decline step down test; EDC: Electronic data capture; EQ-5D-5L: Questionnaire for measuring health-related quality of life; GCP: Good Clinical Practise; IKDC: International Knee Documentation Committee Subjective Knee Form; iPFRN: International Patellofemoral Research Network; IQR: Interquartile range; MCID: Minimal clinically important difference; METC: Medical research ethics committee; in Dutch: medisch-ethische toetsingscommissie; MMRM: Mixed model repeated measures; MPFFA: Maximum Pain-Free Flexion Angle; MRI: Magnetic Resonance Imaging (scan); NFU: Nederlandse Federatie van Universitair Medische Centra; PFP: Patellofemoral Pain; PROMS: Patient Reported Outcome Measures; PT: Physiotherapy program; QoL: Quality of Life; RCT : Randomized controlled trial; ROH: Removal of Hardware; ROM: Range of movement; SAE: Serious adverse event; SD: Standard deviation; TTT: Tibial Tubercle Transfer; TT-TG: Tibial tubercle trochlear groove; VAS: Visual analog scale; WMO: Medical Research Involving Human Subjects Act; In Dutch: Wet Medisch-wetenschappelijk Onderzoek; Declarations Ethics approval and consent to participate This study was approved by the independent Ethical Committee METC Oost-Nederland (protocol number NL80956.091.22) and was registered on ClinicalTrials.gov (study identifier NCT06227806). Written informed consent will be provided by each participant before the start of the study assessments or the intervention. Consent for publication The patient data that will be published are stated in the informed consent. The Dutch consent form for this trial is available upon request. Availability of data and materials Data will be handled according to FAIR principles. After completion of the study, metadata will be available upon request. For access to participant-level data and statistical code, an application can be submitted to the corresponding author. The PT used in the current study is available as supplementary material (see Supplementary file). Competing interests The authors declare that they have no competing interests. Funding This study is funded by the STZ CWZ research fund (33). PFP and osteotomies were prioritized as research topics on the research agenda of the Royal Dutch Orthopaedic Association (NOV) in 2023 (34). This study protocol underwent independent peer review and received approval from the ethical review board. Authors’ contributions SK, MS, MV, and MO designed the study. MO and MV designed the PT. MV wrote the study protocol. SK, MO, SG, VG, MS, and CW adjusted the manuscript. All authors read and approved the final manuscript. Acknowledgments Not applicable. References Boling M, Padua D, Marshall S, Guskiewicz K, Pyne S, Beutler A. Gender differences in the incidence and prevalence of patellofemoral pain syndrome. Scand J Med Sci Sports. 2010;20(5):725-30. DeHaven KE, Lintner DM. Athletic injuries: comparison by age, sport, and gender. Am J Sports Med. 1986;14(3):218-24. Smith BE, Selfe J, Thacker D, Hendrick P, Bateman M, Moffatt F, et al. Incidence and prevalence of patellofemoral pain: A systematic review and meta-analysis. PLoS One. 2018;13(1):e0190892. Crossley KM, Stefanik JJ, Selfe J, Collins NJ, Davis IS, Powers CM, et al. 2016 Patellofemoral pain consensus statement from the 4th International Patellofemoral Pain Research Retreat, Manchester. Part 1: Terminology, definitions, clinical examination, natural history, patellofemoral osteoarthritis and patient-reported outcome measures. Br J Sports Med. 2016;50(14):839-43. Crossley KM, van Middelkoop M, Callaghan MJ, Collins NJ, Rathleff MS, Barton CJ. 2016 Patellofemoral pain consensus statement from the 4th International Patellofemoral Pain Research Retreat, Manchester. Part 2: recommended physical interventions (exercise, taping, bracing, foot orthoses and combined interventions). Br J Sports Med. 2016;50(14):844-52. Witvrouw E, Callaghan MJ, Stefanik JJ, Noehren B, Bazett-Jones DM, Willson JD, et al. Patellofemoral pain: consensus statement from the 3rd International Patellofemoral Pain Research Retreat held in Vancouver, September 2013. Br J Sports Med. 2014;48(6):411-4. Collins NJ, Barton CJ, van Middelkoop M, Callaghan MJ, Rathleff MS, Vicenzino BT, et al. 2018 Consensus statement on exercise therapy and physical interventions (orthoses, taping and manual therapy) to treat patellofemoral pain: recommendations from the 5th International Patellofemoral Pain Research Retreat, Gold Coast, Australia, 2017. Br J Sports Med. 2018;52(18):1170-8. Kastelein M, Luijsterburg PA, Heintjes EM, van Middelkoop M, Verhaar JA, Koes BW, et al. The 6-year trajectory of non-traumatic knee symptoms (including patellofemoral pain) in adolescents and young adults in general practice: a study of clinical predictors. Br J Sports Med. 2015;49(6):400-5. Hott A, Brox JI, Pripp AH, Juel NG, Liavaag S. Patellofemoral pain: One year results of a randomized trial comparing hip exercise, knee exercise, or free activity. Scand J Med Sci Sports. 2020;30(4):741-53. Collins N, Crossley K, Beller E, Darnell R, McPoil T, Vicenzino B. Foot orthoses and physiotherapy in the treatment of patellofemoral pain syndrome: randomised clinical trial. Bmj. 2008;337:a1735. Crossley K, Bennell K, Green S, Cowan S, McConnell J. Physical therapy for patellofemoral pain: a randomized, double-blinded, placebo-controlled trial. Am J Sports Med. 2002;30(6):857-65. van Linschoten R, van Middelkoop M, Berger MY, Heintjes EM, Verhaar JA, Willemsen SP, et al. Supervised exercise therapy versus usual care for patellofemoral pain syndrome: an open label randomised controlled trial. Bmj. 2009;339:b4074. Federatie van Medische Specialisten. Anterieure kniepijn: Richtlijnendatabase; Accessed 22 Jan 2024 [updated 25-01-2022. Available from: https://richtlijnendatabase.nl/richtlijn/anterieure_kniepijn/startpagina_-_anterieure_kniepijn.html. Carlson VR, Boden BP, Shen A, Jackson JN, Yao L, Sheehan FT. The Tibial Tubercle-Trochlear Groove Distance Is Greater in Patients With Patellofemoral Pain: Implications for the Origin of Pain and Clinical Interventions. Am J Sports Med. 2017;45(5):1110-6. Tigchelaar S, van Essen P, Bénard M, Koëter S, Wymenga A. A self-centring osteotomy of the tibial tubercle for patellar maltracking or instability: results with ten-years' follow-up. Bone Joint J. 2015;97-b(3):329-36. Bayoumi T, Benner JL, Stavenuiter MHJ, van der List JP. Tibial tubercle transfer leads to clinically relevant improvement in patients with patellar maltracking without instability: a systematic review and meta-analysis. Knee Surg Sports Traumatol Arthrosc. 2021;29(4):1137-49. Rood A, van Sambeeck J, Koëter S, van Kampen A, van de Groes SAW. A detaching, V-shaped tibial tubercle osteotomy is a safe procedure with a low complication rate. Arch Orthop Trauma Surg. 2020;140(12):1867-72. van Sambeeck JDP, Rood A, Tigchelaar S, van de Groes SAW, Koëter S. Complications of a self-centering sliding tibial tubercle osteotomy for patellofemoral complaints; low incidence of non-union and fracture. Orthop Traumatol Surg Res. 2020;106(5):957-61. World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. Jama. 2013;310(20):2191-4. Castor EDC. Castor Electronic Data Capture 2024 [2 February 2024]. Available from: https://castoredc.com. Koëter S, Diks MJ, Anderson PG, Wymenga AB. A modified tibial tubercle osteotomy for patellar maltracking: results at two years. J Bone Joint Surg Br. 2007;89(2):180-5. Barton CJ, Rathleff MS. 'Managing My Patellofemoral Pain': the creation of an education leaflet for patients. BMJ Open Sport Exerc Med. 2016;2(1):e000086. Djurtoft C, Bruun MK, Riel H, Hoegh MS, Darlow B, Rathleff MS. How do we explain painful non-traumatic knee conditions to adolescents? A multiple-method study to develop credible explanations. Eur J Pain. 2023. Crossley KM, Bennell KL, Cowan SM, Green S. Analysis of outcome measures for persons with patellofemoral pain: which are reliable and valid? Arch Phys Med Rehabil. 2004;85(5):815-22. Kujala UM, Jaakkola LH, Koskinen SK, Taimela S, Hurme M, Nelimarkka O. Scoring of patellofemoral disorders. Arthroscopy. 1993;9(2):159-63. Irrgang JJ, Anderson AF, Boland AL, Harner CD, Kurosaka M, Neyret P, et al. Development and validation of the international knee documentation committee subjective knee form. Am J Sports Med. 2001;29(5):600-13. Tegner Y, Lysholm J. Rating systems in the evaluation of knee ligament injuries. Clin Orthop Relat Res. 1985(198):43-9. Rabin R, de Charro F. EQ-5D: a measure of health status from the EuroQol Group. Ann Med. 2001;33(5):337-43. Ophey MJ, Bosch K, Khalfallah FZ, Wijnands A, van den Berg RB, Bernards NTM, et al. The decline step-down test measuring the maximum pain-free flexion angle: A reliable and valid performance test in patients with patellofemoral pain. Phys Ther Sport. 2019;36:43-50. Barton CJ, De Oliveira Silva D, Morton S, Collins NJ, Rathleff MS, Vicenzino B, et al. REPORT-PFP: a consensus from the International Patellofemoral Research Network to improve REPORTing of quantitative PatelloFemoral Pain studies. Br J Sports Med. 2021;55(20):1135-43. Canisius Wilhelmina Ziekenhuis. Knie expertisecentrum. Accessed 23 Jan 2024 [Available from: https://www.cwz.nl/afdelingen/knie-expertisecentrum/#. Wilkinson MD, Dumontier M, Aalbersberg IJ, Appleton G, Axton M, Baak A, et al. The FAIR Guiding Principles for scientific data management and stewardship. Scientific Data. 2016;3(1):160018. STZ. Samenwerkende Topklinische Ziekenhuizen. Accessed 23 Jan 2024 [Available from: https://www.stz.nl/. Nederlandse Orthopaedische Vereniging (NOV). Onderzoeksagenda Beweegzorg 2023 [Available from: https://www.orthopeden.org/wetenschap/zorgevaluatie/onderzoeksagenda/. Additional Declarations No competing interests reported. Supplementary Files Supplementaryfile.pdf Cite Share Download PDF Status: Published Journal Publication published 15 Jan, 2025 Read the published version in BMC Musculoskeletal Disorders → Version 1 posted Editorial decision: Revision requested 06 Nov, 2024 Reviews received at journal 31 Oct, 2024 Reviewers agreed at journal 07 Oct, 2024 Reviews received at journal 01 Oct, 2024 Reviewers agreed at journal 01 Oct, 2024 Reviewers invited by journal 27 Sep, 2024 Editor assigned by journal 18 May, 2024 Submission checks completed at journal 18 May, 2024 First submitted to journal 11 Apr, 2024 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. 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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-4252434","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Study protocol","associatedPublications":[],"authors":[{"id":308047225,"identity":"dfb0c896-5f3a-4c60-853d-5564bc3f1eb7","order_by":0,"name":"Myrthe P.F. van de Ven","email":"","orcid":"","institution":"Canisius Wilhelmina Ziekenhuis","correspondingAuthor":false,"prefix":"","firstName":"Myrthe","middleName":"P.F. van","lastName":"de Ven","suffix":""},{"id":308047226,"identity":"66092c06-8a5b-495c-80c0-05fc1d988ceb","order_by":1,"name":"Martin Ophey","email":"","orcid":"","institution":"Amsterdam UMC","correspondingAuthor":false,"prefix":"","firstName":"Martin","middleName":"","lastName":"Ophey","suffix":""},{"id":308047227,"identity":"602cc0e6-9b9f-45d7-a4e6-aed90761904a","order_by":2,"name":"Victor van de Graaf","email":"","orcid":"","institution":"Bergman Clinics","correspondingAuthor":false,"prefix":"","firstName":"Victor","middleName":"van","lastName":"de Graaf","suffix":""},{"id":308047228,"identity":"c8b6e639-1c1a-483b-acde-76f5d15d0ea5","order_by":3,"name":"Sebastiaan A.W. van de Groes","email":"","orcid":"","institution":"Radboud University Medical Centre","correspondingAuthor":false,"prefix":"","firstName":"Sebastiaan","middleName":"A.W. van","lastName":"de Groes","suffix":""},{"id":308047229,"identity":"22c2f3b2-4e58-4d5a-8379-3a7828e143b6","order_by":4,"name":"Marijn Sinkeldam","email":"","orcid":"","institution":"Canisius Wilhelmina Ziekenhuis","correspondingAuthor":false,"prefix":"","firstName":"Marijn","middleName":"","lastName":"Sinkeldam","suffix":""},{"id":308047230,"identity":"7cdad6d3-cfc8-46c0-be01-2f9e9cfb2deb","order_by":5,"name":"Charlotte W.H. 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The symptoms are aggravated by activities involving loading the patellofemoral joint during weight bearing on a flexed knee\u0026nbsp;(4). A relatively large proportion of patients (40%) diagnosed with PFP continue to experience symptoms one to six years after diagnosis\u0026nbsp;(5-8).\u003c/p\u003e\n\u003cp\u003eThe treatment goals for PFP are to reduce pain, improve patellofemoral tracking and alignment, and return to the preinjury level of activities. The conservative treatment of PFP with physiotherapy for the quadriceps and hip muscles as the cornerstone has shown varying degrees of success, from no difference\u0026nbsp;(9, 10)\u0026nbsp;to improvement\u0026nbsp;(7, 11, 12). To date, surgical intervention is not recommended in the international PFP consensus statement because high-level evidence about its effects is lacking\u0026nbsp;(7). In the Dutch guideline on \u0026lsquo;anterior knee pain\u0026rsquo;, a multidisciplinary stepped care treatment strategy model is incorporated, consisting of education and an exercise program\u0026nbsp;(13). However, if symptoms persist after 12 weeks, the effect of further exercise therapy or surgery is unknown.\u003c/p\u003e\n\u003cp\u003eCarlson et al.\u0026nbsp;(14)\u0026nbsp;reported that the tibial tubercle-trochlear groove (TT-TG) distance was significantly greater in patients with PFP. In patients with patellar dislocation, a TT-TG \u0026gt;15 mm is considered a clinically relevant anatomical substrate that negatively affects patellofemoral tracking and stability\u0026nbsp;(14, 15). According to a recent meta-analysis, tibial tubercle transfer (TTT) can lead to good results with clinically meaningful improvement in patients with patellofemoral maltracking without instability\u0026nbsp;(16). It is considered a relatively safe procedure with a low complication rate\u0026nbsp;(17, 18). However, no randomized controlled trials (RCT) analysing the value of TTT or comparing TTT with physiotherapy for the treatment of chronic PFP have been published.\u003c/p\u003e\n\u003cp\u003eTo further clarify the additional value of surgery in PFP, a RCT will be conducted to compare TTT in conjunction with a physiotherapy (PT) program versus a PT alone in patients with chronic PFP and a TT-TG \u0026gt; 15 mm.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjectives\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary objective of this study is to compare the between-group difference in knee pain over time for TTT followed by PT versus PT alone in patients aged 18-35 years with chronic PFP. We hypothesize that TTT combined with PT will result in a larger decrease in knee pain than PT alone.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSecondary objectives are to compare the between-group difference in change in 1) \u0026nbsp; knee function, measured by validated Patient Recorded Outcome Measures (PROMs), 2) range of motion (ROM), 3) quality of life (QoL), 4) the functional limitations, and 5) the direct medical costs.\u003c/p\u003e\n\u003cp\u003eThe results of this study can be used to develop and implement a better stepped care treatment strategy for PFP and can be integrated in the national guideline for \u0026ldquo;anterior knee pain\u0026rdquo; (13).\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy design and setting\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA single-centre RCT. All patients will be recruited and included at the Orthopaedics Department of the Canisius Wilhelmina Hospital (CWZ), Nijmegen, the Netherlands. Eligible patients are randomized into two equal groups:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eThe TTT group: 20 PFP patients who will be treated with TTT at the hospital of randomisation, followed by a 12-week supervised PT protocol;\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eThe PT group: 20 PFP patients who will be treated with the same 12-week supervised PT protocol.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThis study will be conducted according to the principles of the Declaration of Helsinki\u0026nbsp;(19)\u0026nbsp;and in accordance with the Medical Research Involving Human Subjects Act (WMO), Good Clinical Practice (GCP) and the General Data Protection Regulation. The study will also be carried out in accordance with local legal requirements. This study was approved by the independent Ethical Committee METC Oost-Nederland (protocol number NL80956.091.22) and was registered on ClinicalTrials.gov (study identifier NCT06227806). Written informed consent will be provided by each participant before the start of the study assessments or the intervention. This protocol adheres to the SPIRIT checklist items.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eParticipants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants between 18 and 35 years of age with at least 12 months of PFP and a tibial tubercle trochlear groove (TT-TG) distance \u0026ge;15 mm on CT or MRI will be recruited at the CWZ hospital in Nijmegen, The Netherlands. PFP is defined as:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003ePain around or behind the patella aggravated by at least one activity that loads the patellofemoral joint (e.g., squatting, running, or jumping);\u003c/li\u003e\n \u003cli\u003ePain during daily life activities, such as: standing for an extended period, walking, or walking upstairs or downstairs.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eParticipants will be excluded when one or more of the following exclusion criteria are met:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003ePrevious knee surgery;\u003c/li\u003e\n \u003cli\u003eReported ligamentous or meniscal injuries of the knee;\u003c/li\u003e\n \u003cli\u003eA history of patellar dislocation; however, subjects with patellar subluxation are included in the study;\u003c/li\u003e\n \u003cli\u003eMalrotational deformity of the lower extremity evident from physical examination;\u003c/li\u003e\n \u003cli\u003eDisabling general illness;\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eOther diagnosed knee injuries, either clinically (such as jumper\u0026apos;s knee) or radiologically (such as osteochondritis dissecans);\u003c/li\u003e\n \u003cli\u003ePatients who cannot undergo surgery;\u003c/li\u003e\n \u003cli\u003ePregnancy;\u0026nbsp;\u003c/li\u003e\n \u003cli\u003ePatients with inability to complete follow-up or with limited understanding of the Dutch language. \u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003ePatient recruitment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll eligible patients will be approached by their treating physician at the orthopaedic department of the CWZ, provided with adequate patient information, and handed out a patient information file (PIF). They will be instructed about the TTT, PT, and possibility to crossover after 12 weeks of the PT. After having had sufficient time (\u0026gt;24 h) to reconsider participation, they will be contacted by a researcher to obtain approval and plan a baseline visit where participants will sign informed consent. Patients will also be asked for permission to approach them for future related research. A list of all eligible patients will be recorded in a screening log, including those that do not wish to participate, as well as the reason if provided.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRandomisation\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients will be enrolled in the study by the study coordinator in the orthopaedic department. All patients who consent to participate in the study and meet the inclusion criteria will be randomized. Patients will be randomised to the TTT + PT: PT only in a 1:1 ratio. The randomisation process will be carried out using a computer-generated randomisation method in the Castor electronic data capture (EDC) system (20), in random blocks of 4. The exact randomisation algorithm is unknown to any of the investigators; hence, concealment of allocation is successful in all patients. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBlinding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNeither the treatment providers nor the study coordinator will be blinded due to the study design (with a blatant intervention).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInterventions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTibial Tubercle Transfer (TTT)\u003c/p\u003e\n\u003cp\u003eThe TTT is a surgical procedure that realigns the patella and, as a result, improves patellar tracking in the trochlear groove. TTT is a relatively safe procedure with a low complication rate (\u0026lt;1% for all major complications) (17, 18). The TTT will be scheduled as soon as possible after randomisation, with a target of \u0026lt;2 weeks. All surgeries will be carried out by either SK or Dr. S. Tigchelaar, both of whom have extensive experience in treating patellofemoral knee disorders. The operative technique used is described previously (21). Patients will be discharged the same day after surgery. Then, a splint phase is started for 4-6 weeks. The physiotherapist will be instructed to contact the study coordinator when the PT begins (see below). After 6 weeks, an outpatient visit with the orthopaedic surgeon is scheduled for a check-up following regular care. At 6 months, there will be an outpatient visit following regular care for evaluation of possible symptoms caused by the hardware. Consequently, removal of hardware (ROH) can be performed if the patient experiences pain derived from the hardware and if complete bone healing is observed on radiographs. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePhysiotherapy (PT) program\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis will start as soon as possible in the PT group and after the splint phase in the TTT group. The PT will consist of three levels and will be supervised by a physiotherapist. According to predefined criteria, the physiotherapist decides whether a patient can step onto the next level within the PT. The PT consists of flexibility, neuromuscular coordination, and strength exercises for the quadriceps and hip muscles. The PT is developed by a team of experienced physiotherapists who are specialized in treating patients with PFP and based upon the most recent physiotherapeutic insights\u0026nbsp;(7). In addition to training, education about PFP is incorporated into the PT according to the most recent insights regarding pain mechanisms\u0026nbsp;(22, 23). Physiotherapists who participate as self-chosen treating health care professionals by patients will be requested to follow the instructional video developed by the REVITALISE study team. Additionally, the three levels of exercise of the PT program are available on the Physitrack\u0026reg; tool for both participating physiotherapists and patients with PFP to improve exercise adherence and support clinical decision-making. In total, there will be 12 sessions with the physiotherapist. In the first three weeks of the PT, patients visit the physiotherapist twice a week. This will occur once a week from week 3 to week 6. This will occur every other week from week 6 to week 12. However, the treating physiotherapist may increase or decrease the number of appointments if needed. The PT is included in the Supplementary file, which contains more detailed information and instructions.\u003c/p\u003e\n\u003cp\u003eTTT and PT versus PT only\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe study involves four outpatient visits (at inclusion/randomisation, 6 weeks after the start of the intervention, after 12 (PT group)/18 weeks (surgery + PT group), and after 26 weeks in both groups). A physical examination will take place at every outpatient visit, with the addition of the decline step-down test (DSDT) at baseline and 12/18 weeks after randomisation. Patients will complete online questionnaires at every outpatient visit and 12 months after randomisation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAfter randomisation, patients will either have a TTT (treatment group) or start with the PT (control group)\u003cem\u003e.\u003c/em\u003e From 12 weeks, there will be the possibility to crossover from the PT group to surgery if the symptoms do not improve. Surgery will then be performed within 2 weeks\u003cem\u003e.\u003c/em\u003e Participants will then follow the same protocol as the TTT group, including the PT program, surveys, and physical measurements.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCriteria for discontinuing or modifying allocated interventions\u003c/p\u003e\n\u003cp\u003eSubjects can leave the study at any time for any reason if they wish to do so without any consequences. The investigator can decide to withdraw a subject from the study for urgent medical reasons. There will be no follow-up of patients who withdraw from the study, but reasons for withdrawal will be recorded. Patients who withdraw from the study will not be replaced.\u003c/p\u003e\n\u003cp\u003eStrategies to improve adherence to interventions\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo improve adherence, patients will receive the PT in text and with visual instructions on the Physitrack app if possible. They will also receive a weekly questionnaire to register the amount of exercising with the physiotherapist and at home, as well as their VAS score during the 12-week PT.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRelevant concomitant care permitted or prohibited during the trial\u003c/p\u003e\n\u003cp\u003ePatients are permitted to take any medication such as paracetamol or other prescribed pain killers. The use of other interventions, such as braces or insoles, is not restricted.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eProvisions for post-trial care\u003c/p\u003e\n\u003cp\u003ePost-trial care will follow standard care, especially for the surgery group. Therefore, we do not expect post-trial harm from participation in this study. There are no specific provisions for post-trial care.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcomes\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePrimary outcome\u003c/p\u003e\n\u003cp\u003eThe main study parameter will be the between-group difference in activity-related knee pain at 10-12 weeks after PT in both groups (week 16-18 in TTT group, week 10-12 in PT group), measured with the 10cm VAS-scale. In this period, an expected plateau phase of pain will be reached. The mean from the three scores (week 10, 11, and 12) will be used to account for variance in pain levels. Participants will assess the maximum pain they had felt during the previous 7 days when participating in activities of daily living such as ascending stairs, descending stairs and standing up from a sitting position. The 10-cm VAS is a valid and responsive tool for evaluating overall pain in patients with PFP\u0026nbsp;(24). A minimal clinically important difference (MCID) of 2 cm or 20% has been reported to reflect real changes in a patient\u0026rsquo;s symptoms\u0026nbsp;(24).\u003c/p\u003e\n\u003cp\u003eSecondary outcomes\u003c/p\u003e\n\u003cp\u003eSecondary outcomes are between-group difference in: pain during the intervention (VAS); functional outcomes (Kujala score, IKDC), activity level (Tegner score), quality of life (EQ-5D-5L), and functional ROM (DSDT) at 12/18 weeks follow-up, as well as the change over time from baseline to 12 months follow-up. Furthermore, this study will provide a global overview of the direct medical costs of surgery + PT compared to PT only treatment.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eVAS\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eDifference in participants\u0026rsquo; assessment of pain during the intervention (TTT + PT or PT only) is measured by the VAS pain score in the weekly questionnaires during the PT, and at 6 and 12 months follow-up. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunctional outcomes\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe Kujala score is a 13-item questionnaire used to evaluate subjective symptoms and functional limitations in patients with PFP (25). Kujala grade ranges from 0-100, with 100 reflecting no signs of PFP. This index shows high validity and is responsive to change (24). To detect improvement, a change of 8-10 points is required (24).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe International Knee Documentation Committee (IKDC) \u0026lsquo;Subjective Knee Form\u0026rsquo; is a tool containing 11 items: 7 on knee symptoms, 2 on function, and 2 on sports activities, resulting in a score ranging from 0-100, with 100 reflecting the highest level of pain and functional restrictions. The IKDC showed high internal consistency (0.92) and test-retest reliability (0.95), with a value change of 9 points indicating true change (26).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eActivity level\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe Tegner activity score consists of 1 item, which scores the level of work- and sport activities on a 10-point scale, with 10 reflecting a high level of activity (27).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eQuality of life\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe health-related quality of life (EQ-5D-5L) questionnaire consists of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that are scored on 5 levels (no problems, slight problems, moderate problems, severe problems, and extreme problems) (28). An index value will be calculated to reflect health status on a scale of 0 to 1, where 1 represents maximum quality of life.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunctional ROM\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe maximum pain-free flexion angle (MPFFA) is measured by the DSDT. The DSDT is a reliable and valid performance test simulating stair descent with almost perfect intra- and interobserver reliability (\u003cem\u003eICC\u003c/em\u003e 0.83-0.85) and an average positive correlation between the DSDT score and the total AKPS score (\u003cem\u003er\u003c/em\u003e\u003cem\u003e\u003csub\u003es\u003c/sub\u003e\u003c/em\u003e= 0.31, \u003cem\u003ep\u0026nbsp;\u003c/em\u003e= .030) (29).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOther study parameters\u003c/p\u003e\n\u003cp\u003eThis study will include items strongly recommended by the International Patellofemoral Research Network (iPFRN) in the REPORT-PFP consensus statement (30). These include demographics, such as \u0026nbsp;age, biological sex, symptom duration, and unilateral/bilateral symptoms (30). Furthermore, physical examination data, such as height and weight (and hence BMI) will be recorded. To evaluate the adherence to the PT, patients will also receive a weekly email during the PT asking how often they have visited the physiotherapist and how often they have executed the PT at home.\u003c/p\u003e\n\u003cp\u003eAny adverse events (AEs) will be monitored, as explained in the \u0026lsquo;Adverse event reporting and harms\u0026rsquo; section. The rate of ROH after surgery will be registered as a separate outcome.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eParticipant timeline\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFigure 1 provides an overview of the study design and procedures.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSample size\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur primary outcome is the between-group difference in overall knee pain 12 weeks after PT and 18 weeks after TTT and PT, measured with the VAS score. Our hypothesis is that the improvement in the TTT group will be greater than the improvement in the PT group.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo detect the superiority of the treat-to-target TTT with PT to PT alone, we calculated the required sample size for an independent samples t-test on the following assumptions: power (1-beta) 0.8, significance level (alpha) 0.05, two-sided testing, MCID mean VAS-pain in TTT + PT: mean 4.1, standard deviation (SD) 2.0, versus PT alone: mean 6.1, and SD 1.9. The SD was based on a study by Bayoumi et al., which compared different surgical techniques for patellar maltracking without instability \u0026nbsp;(16). The MCID was based on a study by Crossley et al., who demonstrated that a change in the VAS score of two points or more is considered clinically relevant and worthwhile for performing surgery (24).\u003c/p\u003e\n\u003cp\u003eBased on these parameters, a sample size of 16 patients per group is needed. Anticipating on a loss to follow-up of 20%, 20 patients per group are needed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFeasibility of recruitment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGiven the \u0026gt;50 TTTs for patients with chronic PFP already performed annually in the CWZ, and accounting for patients who are not willing to participate, we expect to have sufficient numbers of patients for our inclusion within 12 months. The CWZ is a nationally recognized top clinical expertise centre in (patellofemoral) knee surgery and performs approximately 80% of patellofemoral surgeries in the Netherlands, including TTT (31).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData collection methods\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePlans for assessment and collection of outcomes\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe clinical assessment data and PROMs data will be collected in CastorEDC. This data collection will be organized by the study coordinator.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePlans to promote participant retention and complete follow-up\u003c/p\u003e\n\u003cp\u003eParticipants will be closely monitored by the study coordinator to ensure follow-up. To reduce patient burden, data collection will be web-based as often as possible.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData management\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe have created a data management plan in line with the General Data Protection Regulation, which can be viewed upon request. The data will be managed within the online CastorEDC system. This is a secure cloud-based platform that contains an audit trail, automatic range checks, and pseudomized study IDs for all data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConfidentiality\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe type of data that is collected is in line with the General Data Protection Regulation. Study IDs are pseudonymized in CastorEDC for all data. The key to the study ID is safely kept by the study coordinator. The data will be stored for 15\u0026nbsp;years.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical methods for primary and secondary outcomes\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn accordance with the international patellofemoral research network, the REPORT-PFP consensus statement outcome measure description will be adequate (30). The items described in the assessment will be in adequate detail to allow replication. We will report \u003cem\u003en\u003c/em\u003e (%), the mean (SD), and median (interquartile range; IQR) for categorical/descriptive, normally distributed continuous and non-normally distributed continuous data, respectively (30). Results over time will be visualized descriptively in spaghetti plots. The primary analyses will be performed following the intention-to-treat method.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eStatistical analyses will be done using \u003cem\u003eR\u003c/em\u003e software (R Foundation for Statistical Computing, Vienna, Austria).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePrimary endpoint\u003c/p\u003e\n\u003cp\u003eThe primary outcome parameter is the between-group difference in VAS score, at 10-12 weeks after start of the PT (week 16-18 for TTT group). For analysis of the primary parameter, the mean of the three VAS scores at 10, 11, and 12 weeks of the PT \u0026nbsp;in the TTT group will be compared with that of the PT group. Baseline VAS score, biological sex, and treatment group will be included as covariates in a multivariable linear regression analysis.\u003c/p\u003e\n\u003cp\u003eSecondary endpoints\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor the secondary parameters (functional outcomes on the Kujala and IKDC score, activity level on Tegner score, QoL on the EuroQol-5D-5L score, and functional ROM on the DSDT score) at 12 weeks after the start of the PT (week 18 for TTT group), the between-group difference will be assessed using multivariable linear regression analysis in the same manner as the primary endpoint.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo assess the longitudinal clinical effectiveness of both groups, linear mixed models for repeated measures (MMRM) will be used for the secondary outcomes and activity-related knee pain on VAS score during the PT from baseline to 12 months follow-up. MMRMs take the correlation of multiple measurements over time within one patient into account. In the MMRM, this secondary outcomes will be analysed as dependent variables. To evaluate the effect at different time points, the fixed effects will be patient, time, and the treatment group (TTT versus PT only). Time will be included as dummy variable, with baseline as reference.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe main effects for treatment will be reported as difference in means with 95% confidence intervals (CI).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOther study parameters\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe economic aspect will be published based upon an estimation of the direct medical healthcare costs for TTT + PT and conservative care for PFP + PT, including costs for hospital visits, scans, surgery, physiotherapy, prescription medication, and possible readmission. The medical costs are based on resource costs. Furthermore, ROH and complications will be reported.\u003c/p\u003e\n\u003cp\u003eMethods for additional analyses (e.g. subgroup analyses)\u003c/p\u003e\n\u003cp\u003ePer-protocol analyses will be performed including only the patients that did not crossover from the PT to TTT group, for comparison with intention-to treat analysis. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMethods in analysis to handle protocol non-adherence and any statistical methods to handle missing data\u003c/p\u003e\n\u003cp\u003eIn the case of missing outcome values, data will be imputed before analysis using multiple imputation methods.\u003c/p\u003e\n\u003cp\u003ePlans to provide access to the full protocol, participant-level data and statistical code\u003c/p\u003e\n\u003cp\u003eThe trial protocol is available from the corresponding author upon reasonable request. Data will be handled according to the FAIR principles (a guideline to improve the Findability, Accessibility, Interoperability, and Reusability of Digital Assets)\u0026nbsp;(32). After completion of the study, metadata will be available upon request. For access to anonymised participant-level data and statistical code, an application can be submitted to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMonitoring\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData monitoring\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA data monitoring plan has been created and is available upon request. As both groups in this study are within the spectrum of regular care, no data safety monitoring board is installed. Furthermore, since this is a monocentre study, a coordinating centre and trial steering committee are not needed.\u003c/p\u003e\n\u003cp\u003eNo interim analyses will be performed. As the treatments in both groups are within the range of usual care, we do not anticipate differences between the groups that could warrant early cessation of the study due to detrimental effects to the participant.\u003c/p\u003e\n\u003cp\u003eAdverse event reporting and harms\u003c/p\u003e\n\u003cp\u003eAll AEs reported spontaneously by the subject or observed by the investigator or his staff will be recorded. The patient\u0026apos;s general practitioner will receive a letter about the patient\u0026apos;s participation in the study. To prevent underregistration of AEs, we will ask for this information during outpatient visits. AEs will be reported until 12 weeks for the PT group and 18 weeks for the surgery group.\u003c/p\u003e\n\u003cp\u003eElective hospital admission will not be considered a serious adverse event (SAE). Prolongation of initial hospital stay after surgery due to pain or reduced mobility and the need for mobilization under sedation (hardly ever performed after TTT) will not be considered a serious adverse event. The investigator will report all SAEs to the sponsor without any delay after obtaining knowledge of the events. The sponsor will report the SAEs through the web portal ToetsingOnline to the accredited METC, which approved the protocol within 7 days of first knowledge for SAEs that result in death or are life threatening, followed by a period of a maximum of 8 days to complete the initial preliminary report. All other SAEs will be reported within a maximum of 15 days after the sponsor has first knowledge of the serious adverse events. SAEs will be reported until 12 weeks for the PT group and 18 weeks for the surgery group.\u003c/p\u003e\n\u003cp\u003eAuditing \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMonitoring will be performed once per year. It will involve monitoring the investigator site file, informed consent, SAEs, in- and exclusion criteria, among others. Monitoring will be performed according to Nederlandse Federatie van Universitair Medische Centra (NFU) guidelines and a monitoring plan by a monitor from the CWZ academy.\u003c/p\u003e\n\u003cp\u003eProtocol amendments\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll amendments will be reported to the ethical review committee that gave a favourable opinion. Non-substantial amendments will not be notified to the accredited ethical review committee or the competent authority but will be recorded and filed by the investigator.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDissemination plans\u003c/p\u003e\n\u003cp\u003eOverall trial results will be communicated to participants, presented at (inter)national conferences, and reported in peer-reviewed journals. There are no publication restrictions. Medically relevant incidental findings will be shared with the study subject.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe REVITALISE study is the first RCT to compare surgical intervention followed by PT to PT alone in patients with chronic PFP. This study\u0026rsquo;s results will gain insight into the most effective treatment for patients with chronic PFP and will enhance our treatment of this high burden disease with currently a high variability of provided care\u0026nbsp;(13). This variation seems to be not or weakly associated with patient characteristics, elucidating the need for a more standardized approach to prevent over- or under treatment. The study will answer the question whether patients receiving TTT followed by \u0026nbsp;PT have less pain and better functional outcomes than those receiving PT alone. In addition to measuring the effectiveness of TTT plus PT versus PT alone, a range of other outcomes will be assessed (e.g., physical function, complications, direct medical \u0026nbsp;costs), to provide a broader view of the effect of both treatments.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe strengths of the study include the randomized controlled design supported with multiple involved professions. Physiotherapists are involved in the design of the PT. Orthopaedic surgeons are involved in the TTT protocol. Since this is a single-centre study, little or no variation in surgical technique is expected.\u003c/p\u003e\n\u003cp\u003eThis study has several limitations. First, the crossover design potentially affects long-term (i.e., \u0026gt;12 weeks) comparisons of the groups, as well as induces bias in cases where patients become less motivated to follow physiotherapy. However, as the primary analysis is according to the intention-to-treat principles, we do not expect this to have a major impact. Second, at the time of presentation at the hospitals, patients will have had different treatments, i.e., the care given by the family physician, the outpatient physiotherapist, or other involved professionals. In our physiotherapy program, special care is given to education of the patient about PFP, as well as a focus on building balance and strength in multiple muscle groups, not only the quadriceps. Third, for logistical reasons, it is not possible for all participants to receive physiotherapy from the same physiotherapist. To limit protocol variations, we will contact each physiotherapist to explain the research design, the PT, and the need to adhere to this program. Simultaneously, the physiotherapist should tailor the program to the participants, as their individual needs and limitations are always the highest priority.\u003c/p\u003e\n\u003cp\u003eThe results of this study will address an important evidence gap and will have a significant impact on the care of patients with chronic PFP.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTRIAL STATUS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study is currently open for inclusion. Recruitment started on 24 October 2023, and the expected end date of recruitment is 24 October 2024.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAE: Adverse event;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAKPS: Anterior Knee Pain Score (Kujala score);\u003c/p\u003e\n\u003cp\u003eBMI: Body Mass Index;\u003c/p\u003e\n\u003cp\u003eCI: Confidence Interval;\u003c/p\u003e\n\u003cp\u003eCT: Computer Tomography (scan);\u003c/p\u003e\n\u003cp\u003eCWZ: Canisius Wilhelmina Ziekenhuis;\u003c/p\u003e\n\u003cp\u003eDSDT: Decline step down test;\u003c/p\u003e\n\u003cp\u003eEDC: Electronic data capture;\u003c/p\u003e\n\u003cp\u003eEQ-5D-5L: Questionnaire for measuring health-related quality of life;\u003c/p\u003e\n\u003cp\u003eGCP: Good Clinical Practise;\u003c/p\u003e\n\u003cp\u003eIKDC: International Knee Documentation Committee Subjective Knee Form;\u003c/p\u003e\n\u003cp\u003eiPFRN: International Patellofemoral Research Network;\u003c/p\u003e\n\u003cp\u003eIQR: Interquartile range;\u003c/p\u003e\n\u003cp\u003eMCID: Minimal clinically important difference;\u003c/p\u003e\n\u003cp\u003eMETC: Medical research ethics committee; in Dutch: medisch-ethische toetsingscommissie;\u003c/p\u003e\n\u003cp\u003eMMRM: Mixed model repeated measures;\u003c/p\u003e\n\u003cp\u003eMPFFA: Maximum Pain-Free Flexion Angle;\u003c/p\u003e\n\u003cp\u003eMRI: Magnetic Resonance Imaging (scan);\u003c/p\u003e\n\u003cp\u003eNFU: Nederlandse Federatie van Universitair Medische Centra;\u003c/p\u003e\n\u003cp\u003ePFP: Patellofemoral Pain;\u003c/p\u003e\n\u003cp\u003ePROMS: Patient Reported Outcome Measures;\u003c/p\u003e\n\u003cp\u003ePT: Physiotherapy program;\u003c/p\u003e\n\u003cp\u003eQoL: Quality of Life;\u003c/p\u003e\n\u003cp\u003eRCT : Randomized controlled trial;\u003c/p\u003e\n\u003cp\u003eROH: Removal of Hardware;\u003c/p\u003e\n\u003cp\u003eROM: Range of movement;\u003c/p\u003e\n\u003cp\u003eSAE: Serious adverse event;\u003c/p\u003e\n\u003cp\u003eSD: Standard deviation;\u003c/p\u003e\n\u003cp\u003eTTT: Tibial Tubercle Transfer;\u003c/p\u003e\n\u003cp\u003eTT-TG: Tibial tubercle trochlear groove;\u003c/p\u003e\n\u003cp\u003eVAS: Visual analog scale;\u003c/p\u003e\n\u003cp\u003eWMO: Medical Research Involving Human Subjects Act; In Dutch: Wet Medisch-wetenschappelijk Onderzoek;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the independent Ethical Committee\u0026nbsp;METC Oost-Nederland (protocol number NL80956.091.22) and was registered on ClinicalTrials.gov (study identifier NCT06227806). Written informed consent will be provided by each participant before the start of the study assessments or the intervention.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient data that will be published are stated in the informed consent. The Dutch consent form for this trial is available upon request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData will be handled according to FAIR principles. After completion of the study, metadata will be available upon request. For access to participant-level data and statistical code, an application can be submitted to the corresponding author. The PT used in the current study is available as supplementary material (see Supplementary file).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is funded by the STZ CWZ research fund\u0026nbsp;(33). PFP and osteotomies were prioritized as research topics on the research agenda of the Royal Dutch Orthopaedic Association (NOV) in 2023\u0026nbsp;(34). This study protocol underwent independent peer review and received approval from the ethical review board.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSK, MS, MV, and MO designed the study. MO and MV designed the PT. MV wrote the study protocol. SK, MO, SG, VG, MS, and CW adjusted the manuscript. All authors read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBoling M, Padua D, Marshall S, Guskiewicz K, Pyne S, Beutler A. Gender differences in the incidence and prevalence of patellofemoral pain syndrome. Scand J Med Sci Sports. 2010;20(5):725-30.\u003c/li\u003e\n\u003cli\u003eDeHaven KE, Lintner DM. Athletic injuries: comparison by age, sport, and gender. Am J Sports Med. 1986;14(3):218-24.\u003c/li\u003e\n\u003cli\u003eSmith BE, Selfe J, Thacker D, Hendrick P, Bateman M, Moffatt F, et al. Incidence and prevalence of patellofemoral pain: A systematic review and meta-analysis. PLoS One. 2018;13(1):e0190892.\u003c/li\u003e\n\u003cli\u003eCrossley KM, Stefanik JJ, Selfe J, Collins NJ, Davis IS, Powers CM, et al. 2016 Patellofemoral pain consensus statement from the 4th International Patellofemoral Pain Research Retreat, Manchester. Part 1: Terminology, definitions, clinical examination, natural history, patellofemoral osteoarthritis and patient-reported outcome measures. Br J Sports Med. 2016;50(14):839-43.\u003c/li\u003e\n\u003cli\u003eCrossley KM, van Middelkoop M, Callaghan MJ, Collins NJ, Rathleff MS, Barton CJ. 2016 Patellofemoral pain consensus statement from the 4th International Patellofemoral Pain Research Retreat, Manchester. Part 2: recommended physical interventions (exercise, taping, bracing, foot orthoses and combined interventions). Br J Sports Med. 2016;50(14):844-52.\u003c/li\u003e\n\u003cli\u003eWitvrouw E, Callaghan MJ, Stefanik JJ, Noehren B, Bazett-Jones DM, Willson JD, et al. 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The decline step-down test measuring the maximum pain-free flexion angle: A reliable and valid performance test in patients with patellofemoral pain. Phys Ther Sport. 2019;36:43-50.\u003c/li\u003e\n\u003cli\u003eBarton CJ, De Oliveira Silva D, Morton S, Collins NJ, Rathleff MS, Vicenzino B, et al. REPORT-PFP: a consensus from the International Patellofemoral Research Network to improve REPORTing of quantitative PatelloFemoral Pain studies. Br J Sports Med. 2021;55(20):1135-43.\u003c/li\u003e\n\u003cli\u003eCanisius Wilhelmina Ziekenhuis. Knie expertisecentrum. Accessed 23 Jan 2024 [Available from: https://www.cwz.nl/afdelingen/knie-expertisecentrum/#.\u003c/li\u003e\n\u003cli\u003eWilkinson MD, Dumontier M, Aalbersberg IJ, Appleton G, Axton M, Baak A, et al. The FAIR Guiding Principles for scientific data management and stewardship. Scientific Data. 2016;3(1):160018.\u003c/li\u003e\n\u003cli\u003eSTZ. Samenwerkende Topklinische Ziekenhuizen. Accessed 23 Jan 2024 [Available from: https://www.stz.nl/.\u003c/li\u003e\n\u003cli\u003eNederlandse Orthopaedische Vereniging (NOV). Onderzoeksagenda Beweegzorg 2023 [Available from: https://www.orthopeden.org/wetenschap/zorgevaluatie/onderzoeksagenda/.\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":"bmc-musculoskeletal-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmsd","sideBox":"Learn more about [BMC Musculoskeletal Disorders](http://bmcmusculoskeletdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12891","title":"BMC Musculoskeletal Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Patellofemoral pain, tibial tubercle transfer, physiotherapy, randomized controlled trial","lastPublishedDoi":"10.21203/rs.3.rs-4252434/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4252434/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003ePatellofemoral pain (PFP) is a common musculoskeletal disorder resulting in anterior knee pain. Physiotherapy is the current standard treatment, while surgical intervention (tibial tubercle transfer [TTT]) is reserved for chronic cases when nonoperative treatment has failed. However, to date, no randomized controlled trials (RCT) have compared TTT combined with a physiotherapy (PT) program PT to PT alone as the initial treatment for PFP.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eA single-centre RCT in patients with chronic PFP (\u0026gt;1 year) will be randomized to either TTT followed by PT (n=20) or to PT alone (n=20). The primary outcome is knee pain at 18 weeks for the TTT group and at 12 weeks for the PT group, measured by the visual analog scale (VAS). Secondary outcomes include Patient Recorded Outcome Measures (PROMs) using the Kujala score, International Knee Documentation Committee (IKDC) ‘Subjective Knee Form’, Tegner Activity score and EuroQol 5D-5L for quality of life. Range of motion (ROM) is measured using the decline step-down test (DSDT). The difference in direct medical costs will also be assessed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion: \u003c/strong\u003eThe REVITALISE study is the first randomized study to compare surgical intervention (TTT) followed by PT to PT alone in patients with chronic PFP. This study will generate level-1 evidence on the most effective treatment for chronic PFP, which can be integrated into the national guideline to aid orthopaedic surgeons and physiotherapists in their decision-making and ultimately improve our care for patients with chronic PFP.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudy Identifier NCT06227806, registered on 26 Jan 2024 on ClinicalTrials.gov. The study underwent independent peer review and received approval from the ethical review board (number NL80956.091.22).\u003c/p\u003e","manuscriptTitle":"SurgeRy and physiothErapy Versus physIotherapy only for chronic paTellofemorAL paIn: study protocol for a randomiSed controllEd trial (REVITALISE)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-04 21:56:32","doi":"10.21203/rs.3.rs-4252434/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-11-06T17:45:47+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-31T19:50:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"180587170332839588641944006782516036976","date":"2024-10-07T09:13:53+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-01T11:29:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"19143769305131046147989331104292346898","date":"2024-10-01T09:29:16+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-09-27T09:13:31+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-05-19T02:09:50+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-05-19T02:09:49+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Musculoskeletal Disorders","date":"2024-04-11T12:26:14+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-musculoskeletal-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmsd","sideBox":"Learn more about [BMC Musculoskeletal Disorders](http://bmcmusculoskeletdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12891","title":"BMC Musculoskeletal Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"503819d3-36cc-4a88-a941-db1fab81ded2","owner":[],"postedDate":"June 4th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-01-20T16:01:50+00:00","versionOfRecord":{"articleIdentity":"rs-4252434","link":"https://doi.org/10.1186/s12891-024-08226-y","journal":{"identity":"bmc-musculoskeletal-disorders","isVorOnly":false,"title":"BMC Musculoskeletal Disorders"},"publishedOn":"2025-01-15 15:57:31","publishedOnDateReadable":"January 15th, 2025"},"versionCreatedAt":"2024-06-04 21:56:32","video":"","vorDoi":"10.1186/s12891-024-08226-y","vorDoiUrl":"https://doi.org/10.1186/s12891-024-08226-y","workflowStages":[]},"version":"v1","identity":"rs-4252434","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4252434","identity":"rs-4252434","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}