REGENETEN™ Bioinductive Implant System in Full-thickness Tears

Study Overview
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Brief Summary
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The study is designed to assess the safety and efficacy of Arthroscopic rotator cuff repair (ARCR) augmented with REGENETEN in subjects requiring full-thickness rotator cuff tear repair or revision repair versus Arthroscopic rotator cuff repair alone.

Detailed Description
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This study is a prospective, multi-center, randomized, controlled clinical study in the treatment of full thickness tears of the rotator cuff (large or massive ≥3 cm in AP or ML according to Cofield classification). The subjects meeting the inclusion/exclusion criteria specified in the protocol will receive either ARCR augmented with REGENETEN or ARCR alone. Subjects enrolled into the revision repair subject group will receive ARCR augmented with REGENETEN. The clinical follow-up evaluation will be performed preoperatively (Baseline), 2 weeks, 6 weeks, 3, 6, 12, and 24 months after surgery, respectively using subjective outcome measures, objective measures of movement and an MRI scan to assess the integrity of the repair and assess the re-tear rate. Health economic data will also be collected.

Official Title
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A Prospective, Multi-center, Randomized Controlled Study to Evaluate the Safety and Efficacy of ARCR Augmented With REGENETEN™ Bioinductive Implant System in Full-thickness Tears (Large or Massive) Repair Versus ARCR Alone

Conditions
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Rotator Cuff Injuries

Intervention / Treatment
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* Device: Arthroscopic rotator cuff repair with REGENETEN™ Bioinductive Implant augmentation
* Procedure: Arthroscopic rotator cuff repair
* Device: Arthroscopic rotator cuff repair for revision surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject requires Arthroscopic rotator cuff repair (ARCR); Subjects with a diagnosis of a symptomatic primary or recurrent (revision repair subject group), large or massive tear (≥ 3 cm AP/ML) of the supraspinatus and/or infraspinatus tendons amenable to repair. For screening purposes, a ≥ 2 cm AP/ML tear as measured on MRI will be eligible to proceed to the operative visit but will have to be confirmed as ≥ 3 cm on arthroscopy using a calibrated probe to proceed; Subject is > 40 years of age (no upper limit); Subject provides written informed consent for study participation using an Independent Ethical Committee (IEC) / Institutional Review Board (IRB) approved consent form; Subject is willing and able to participate in required follow-up visits and is able to complete study activities. Exclusion Criteria: Subjects who are unable to tolerate magnetic resonance imaging (MRI), due to psychiatric or medical contraindications; Subjects with Samilson-Prieto osteoarthritis > 2; Subjects with current or prior infection of the ipsilateral shoulder; Subjects with known hypersensitivity to bovine-derived materials; Subjects with known inflammatory arthropathy, history of inflammatory arthropathy, or chronic joint disease; Subjects with prior shoulder surgery (not including rotator cuff repair [revision repair subject group only], biceps tenodesis/tenotomy, distal clavicle excision [DCE], subacromial decompression); Subjects with an irreparable or partially reparable rotator cuff tear; Subjects with a subscapularis tear requiring repair; Subjects requiring a concomitant labral fixation procedure; Subjects requiring a concomitant os acromiale fixation procedure; Subjects with glenohumeral joint instability (multiple dislocations/subluxations); Subjects with a subacromial or intra-articular injection within 3 months prior to surgery; Subjects with condition(s) that contraindicate or complicate outcomes of ARCR e.g., > Hamada 3 rotator cuff arthropathy on X-ray, Goutallier atrophy > Grade 3, proximal humeral fracture or scapular fracture, avascular necrosis of the humeral head or glenoid, history of immunodeficiency disorders, history of chronic inflammatory disorders, oral or injected steroid use in last 4 weeks; Subjects who are pregnant or breast feeding; Subjects who are currently involved in any injury litigation or workers compensation claims; Subjects who are enrolled, or plan to enroll, in another clinical trial during this study that would affect the outcomes of this study; Subjects with a history of noncompliance with medical treatment, physical therapy (PT)/rehabilitation, or clinical study participation Subject who, in the opinion of the Investigator, has an emotional or neurological condition that would pre-empt their ability or willingness to participate in the study including mental illness, mental retardation, and drug or alcohol abuse; Subjects who do not meet the indication or are contraindicated according to specific Smith+Nephew REGENETEN System's Instructions for Use (IFUs); Subject that meets the definition of a Vulnerable Subject per ISO14155:2020 Section 3.44.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARCR augmented with REGENETEN™ Bioinductive Implant<br>During the ARCR procedure, the REGENETEN™ Bioinductive Implant is covering the tendon and attached to the bone and the tendon with small anchors. | Device: Arthroscopic rotator cuff repair with REGENETEN™ Bioinductive Implant augmentation<br>* The Arthroscopic rotator cuff repair aims at repairing the rotator cuff following tendon tear. The REGENETEN Bioinductive Implant is a medical device intended for the management and protection of tendon injuries. The REGENETEN Bioinductive Implant is indicated for the management and protection of rotator cuff tendon injuries in which there has been no substantial loss of tendon tissue. The REGENETEN Bioinductive Implant is a bioabsorbable implant device that provides a layer of collagen over injured tendons. The implant is designed to provide a layer of collagen between a flat tendon and the surrounding tissue. After hydration, the implant is an easy-to-handle, pliable, nonfriable, porous collagen sheet.<br>|
| Sham Comparator: ARCR alone<br>The rotator cuff is repaired during arthroscopic standard procedure. No product is added for healing | Procedure: Arthroscopic rotator cuff repair<br>* The Arthroscopic rotator cuff repair aims at repairing the rotator cuff following tendon tear without supplement.<br>|
| Other: ARCR revision group<br>ARCR revision group allows treatment of subjects having recurrent tears, ARCR supplemented with REGENETEN | Device: Arthroscopic rotator cuff repair for revision surgery<br>* The Arthroscopic rotator cuff repair can also occur in recurrent tears. The REGENETEN Bioinductive Implant will be applied during the ARCR procedure.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 months retear rate | The cumulative 6 months retear rate after full-thickness ARCR augmented with REGENETEN versus ARCR alone. Failure is defined as Sugaya Type IV or V retear/recurrence (fullthickness discontinuity seen on both coronal and oblique sagittal MRI images). | 6 months post surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Retear rate | Cumulative 3, 6, 12, and 24 months retear rate after fullthickness ARCR augmented with REGENETEN (confirmed on MRI) versus ARCR alone. Failure is defined as Sugaya Type IV or V retear/recurrence (full-thickness discontinuity seen on both coronal and oblique sagittal MRI images). | 3, 6, 12, and 24 months | 
| Oxford Shoulder Score (OSS) | The Oxford Shoulder Score (OSS) is a questionnaire for the assessment of outcomes of shoulder surgery, which can reduce the observer's errors in the evaluation. It contains 12- item patient-reported outcome (PRO) measures specifically designed and developed for assessing outcomes of shoulder surgery such as assessing the impact on patients' quality of life of degenerative conditions (e.g., arthritis and rotator cuff problems). The OSS consists of 12 questions each scored 0 to 4 (0=unbearable, 1=severe, 2=moderate, 3=mild, 4=none) with 4 representing the best outcome. When the 12 items are summed, this produces overall scores that run from 0 to 48, with zero (0) representing a severe shoulder problem and 48 representing no related problem. Higher scores represent better clinical outcomes. | Baseline, 3, 6, 12 and 24 months | 
| Western Ontario Rotator Cuff (WORC)/Chinese version WORC (C-WORC) Index) | The WORC/C-WORC Index is self-administered, and includes a 5 different domains (physical symptoms, sports and recreation, work, social function, and emotions). Each question uses a visual analog scale (VAS) representing a 100-point scale ranging from 0 to 100. The maximum score is 2100 (worst possible symptoms). Zero (0) represents no symptoms at all. The final score can also be presented as a percentage by subtracting the total from 2100, dividing by 2100, and multiplying by 100. This will give you an overall percentage. The total final WORC/CWORC Index scores can, therefore, range from 0% (lowest functional status level) to 100% (highest functional status level). | Baseline, 3, 6, 12 and 24 months | 
| Constant-Murley Score | The Constant-Murley Score is a validated assessment of pain and shoulder functionality. The Constant Score is divided into 4 subscales: pain (15 points; VAS score range of 0-15), activities of daily living (20 points; range 0=worst, 5=best), strength (25 points; 1 point given per 0.5 kg of weights raised), and range of motion - forward flexion, external rotation, abduction and internal rotation of the shoulder (40 points; range 0=worst, 10=best). The higher the score, the higher the quality of function. | Baseline, 3, 6, 12 and 24 months | 
| Subjective shoulder value (SSV) | Overall performance of full-thickness ARCR augmented with REGENETEN versus ARCR alone at Baseline and at 3, 6, 12 and 24 months assessed by the Subjective Shoulder Value (SSV). The SSV is defined as a patient's subjective shoulder assessment expressed as a percentage of an entirely normal shoulder, which would score 100% (0% to 100% scale with 100% being normal). | Baseline, 3, 6, 12 and 24 months | 
| EuroQol 5 Dimension 5 Level (EQ-5D-5L) Score | The EQ-5D-5L score consists of two parts: a descriptive system and a visual analogue scale. The descriptive system is used to describe the subject's health state and consists of five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels to choose the most appropriate answer: no problems, slight problems, moderate problems, severe problems and extreme problems. The subject is asked to indicate his/her health state by marking the most appropriate statement in each of the five areas. The visual analogue scale records the subject's self-rated health on a vertical visual analogue scale.The endpoints on the scale are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome as judged by the individual respondents. | Baseline, 3, 6, 12 and 24 months | 
| Patient satisfaction Questionnaire Outcome | The Patient Satisfaction Questionnaire is a simple subjective assessment of the success of surgery from the patient's perspective. Pre-Op: will be documented on a visual analogue score of 0-100. Rated by the subject with 0 is the least satisfied, 100 the most satisfied.Post-Op:This includes the VAS Patient Satisfaction Score as for pre-Op and additional five questions ask of the patient:1. How well did the surgery relieve the pain? 2. How well did the surgery increase your ability to perform regular activities? 3. How well did the surgery allow you to perform heavy work or sport activities (if allowed by Dr)? 4. How well did the surgery meet your expectations? Questions rated by the patient with excellent, very good,good, fair and poor. 5. Would you have the operation again if needed on another joint? Question rated by the patient with Definitely yes, Probably yes, Possibly not, Definitely not Rated by the subject with 0 is the least satisfied, 100 the most satisfied. | Baseline, 3, 6, 12 and 24 months | 
| Pain, Visual analog scale (VAS) Score | Overall performance of full-thickness ARCR augmented with REGENETEN versus ARCR alone at Baseline and at 3, 6,12 and 24 months assessed by the VAS Pain Score. Pain is assessed on a 100-point scale ranging from 0 to 100, with zero (0) representing no pain and 100 representing the worst pain imaginable | Baseline, 2 weeks, 6 weeks, 3 and 6 months | 
| MRI Tendon Findings in ARCR augmented with REGENETEN versus ARCR alone via Sugaya Score postoperatively | The Sugaya score will be used to determine postoperative cuff integrity through magnetic resonance imaging classified into 5 categories: Type I to Type V. Type I indicates sufficient thickness with homogenously low intensity. Type II indicates sufficient thickness with partial high intensity. Type III indicates insufficient thickness without discontinuity. Type IV indicates presence of a minor discontinuity, suggesting a small full-thickness tear. Type V indicates the presence of a major discontinuity, suggesting a medium or large full-thickness tear. | Baseline, 3, 6, 12 and 24 months | 
| MRI Tendon Findings in ARCR augmented with REGENETEN versus ARCR alone via Goutallier Classification postoperatively | The Goutallier classification will be used to classify the fatty infiltration of the rotator cuff. The Goutallier classification ranges from a grade of 0 indicating a completely normal muscles without any fatty streaks to a grade of 4 which indicates that more fat than muscle is present. | Baseline, 3, 6, 12 and 24 months | 
| Total tendon thickness, tendon length will be assessed by MRI Tendon Findings in ARCR augmented with REGENETEN versus ARCR alone postoperatively | Tendon thickness, length will be assessed by MRI | Baseline, 3, 6, 12 and 24 months | 
| Size of retear: anteroposterior [AP]/mediolateral [ML]) postoperatively | Size of retear will be based on MRI Tendon Findings in ARCR augmented with REGENETEN versus ARCR alone. | Baseline, 3, 6, 12 and 24 months | 
| Shape of retear postoperatively | Shape of retear will be based on MRI Tendon Findings in ARCR augmented with REGENETEN versus ARCR alone | Baseline, 3, 6, 12 and 24 months | 
| Outcome of Return to Work Questionnaire in ARCR augmented with REGENETEN versus ARCR alone | Generic questionnaire, covering work related questions,including demographics on laborer/sedentary. | Baseline, 2 weeks, 6 weeks, 3, 6, 12 and 24 months | 
| Cumulative duration of opioid use in ARCR augmented with REGENETEN versus ARCR alone | Self-reported opioid use diary completed by the patient on a daily basis, from day 0-14, documenting opioid use. Consumption daily (YES/NO) x14 days, 'Have you taken any opioid medication today for shoulder pain?' Y/N . | 2 weeks | 
| Total operative time ARCR augmented with REGENETEN versus ARCR alone | Total operative time ARCR augmented with REGENETEN versus ARCR alone. | Intra-operative time | 
| Sling type and mobilization time in ARCR augmented with REGENETEN versus ARCR alone | The type of sling will be collected and presented for each treatment arm summarizing if standard sling, shoulder immobilizer, abduction sling, ER sling, or other were advised and mobilization time will be calculated for both arms summarizing mobilization duration. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rotator cuff tendon, Full thickness tears, REGENETEN Bioinductive Implant System