Study report CAMOPED study

1. Summary The following report was prepared as part of a trial guideline in accordance with Section 137e (1) SGB V to evaluate the benefits of the use of CAM splints for self-application by patients in the post-surgical rehabilitative treatment of ruptures of the anterior cruciate ligament. The primary aim of the study project was to test the hypothesis that rehabilitation with CAMOped in addition to standardised rehabilitation (intervention group, IG) is superior to standardised rehabilitation alone (control group, KG) in terms of knee joint function measured with the sIKDC (subjective assessment) at 6 weeks post surgery (FU2) compared to the time of assessment immediately post-surgical (T4). Between June 2020 and January 2023, 105 patients (m:w 62:43, age 33 ± 11 years) were randomised in a stratified manner (50 IG and 55 KG) and included in the study, which was evaluated using an intention-to-treat (ITT) approach. 88 subjects had a simple anterior cruciate ligament rupture, 17 subjects also received a meniscal intervention. The study was discontinued for ethical reasons when the CPM splint was included in standard care and thus not carried out in accordance with the protocol for the CG in January 2023. There were 87 usable data sets (42 IG and 45 KG) for analysing the primary research question. With regard to the relevant preoperative influencing variables (age, Tegner score, injury, sex ratio or oIKDC) at the time of study inclusion (T0), both study groups were equal. In the IG, 5 patients received an additional meniscus intervention (10% of the IG), while in the KG the proportion was 22% with 12 patients. The CAM splint was used for a period of 3 weeks preoperatively and 6 [5-7] weeks post-surgical. At post surgery discharge (time point T4), knee joint function (sIKDC) was significantly higher (higher knee joint function) in the IG compared to the KG (n=87, 33.0 [23.0 - 46.0] vs. 28.0 [21.0 - 33.0], p=0.024). Three weeks post-surgical (FU1, n=85), knee joint function was the same in both groups. At the time of the follow-up examinations after 6 weeks (FU2, time of recording the primary endpoint), there was no difference in the sIKDC score between the intervention and control groups (n=87, 56.5 [48.0 - 64.0] vs. 54.0 [48.0 - 63.0], p=n.s.). The prespecified analysis, in which the change at the follow-up time after 6 weeks post-surgical (FU2) was analysed in relation to the assessment at post surgery discharge (T4), showed that the absolute change in knee joint function was significantly lower in the IG (n= 42) than in the KG (24.5 [12.0 - 31.0] vs. 29.0 [18.0 - 35.0], p=0.041). After 12 weeks (FU3), the subjective knee joint function was identical in both treatment groups. During the one-year follow-up period, 91 adverse events occurred, including 8 serious adverse events, each unrelated to the investigational product. From 12/2021 - the date on which the CPM splint was included in standard care - the high number of refusals to participate in a study without CPM splints in the control group by patients and the number of protocol violations and dropouts was striking. After conducting the interim analysis on 19 September 2022 and subsequent discussion with the LKP and the principal investigators, this led to the principal investigator discontinuing the study for ethical reasons. A respective letter in german from the PI to the sponsor of the study can be requested from the study contact. Competing Interest Statement The authors have declared no competing interest. Clinical Trial DRKS: 00021739 Funding Statement This study was funded by OPED GmbH Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics Committee: The Ethics Committee of Charite, Universitaetsmedizin Berlin, Campus Charite Mitte, Chariteplatz 1, 10117 Berlin The ethics vote (german language) will be sent upon request. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes about the trial study “Multicenter, randomised, controlled, single-blinded clinical study to prove the effectiveness of an active movement splint (CAMOped) for home self-application in the treatment of ruptures of the anterior cruciate ligament in addition to standardised physiotherapeutic rehabilitation” Can MObility Post surgery Enhance Direct rehabilitation - CAMOPED Independent medical and scientific advice: PD Dr. Caroline Schmidt-Lucke, MEDIACC GmbH, Sächsische Straße 70, 10707 Berlin, Germany, Phone: +49 30 521 044 80, Fax: +49 30 521 044 83, E-mail: caroline.schmidt-lucke{at}mediacc.de Consultant statistician: Dr. Jan Multmeier, c/o MEDIACC GmbH, E-mail: mail{at}janmultmeier.de Client: OPED GmbH, Medical Park 1, D-83626 Valley/Oberlaindern, Germany Additional information on the following study report: The following document has been translated by an automatic translator. Appendices can be issued by the publisher in German on request. Please contact anne.schraplau{at}mediacc.org Data Availability All data produced in the present study are available upon reasonable request to the authors List of abbreviations - Abbreviation - Meaning - ACL - anterior cruciate ligament - AC - Adverse event - ADE - Undesirable effects of the product (adverse device effect) - CAM - Continuous active motion (active motion rail) - CPM - Continuous passive motion (passive motion rail) - DD - Product defect (device defect) - EC - Ethics Committee - FU - Follow-up (follow-up examination) - G-BA - Joint Federal Committee - GAS - Goal Attainment Scale - IG - Intervention group - IQWiG - Institute for Quality and Efficiency in Health Care - CG - Control group - KOOS - Knee Injury and Osteoarthritis Outcome Score - LERAS-13 - Lower Extremity Early Rehabilitation Score-13 - LKP - Head of the clinical trial (principal investigator) - LCL - Lateral collateral ligament - MCID - Minimal clinically important difference - MCL - medial collateral ligament - PROM - Passive range of motion - RCT - randomised controlled trial (randomised controlled study) - SADE - Serious undesirable effects of the product (serious adverse device effect) - SAE - Serious adverse event - SCB - Substantial clinical benefit - IKDC - International Knee Documentation committee - TMF - Trial Master File - ACL - Anterior cruciate ligament - ACLR - Anterior cruciate ligament rupture