REGENETEN™ Bioinductive Implant System in Full-thickness Tears

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: October 2022

Detailed Description

This study is a prospective, multi-center, randomized, controlled clinical study in the treatment of fullthickness 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 REGENTEN. 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 retear rate. Health economic data will also be collected.

Interventions

  • Device: Arthroscopic rotator cuff repair with REGENETEN™ Bioinductive Implant augmentation
    • 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.
  • Procedure: Arthroscopic rotator cuff repair
    • The Arthroscopic rotator cuff repair aims at repairing the rotator cuff following tendon tear without supplement.
  • Device: Arthroscopic rotator cuff repair for revision surgery
    • The Arthroscopic rotator cuff repair can also occur in recurrent tears. The REGENETEN Bioinductive Implant will be applied during the ARCR procedure.

Arms, Groups and Cohorts

  • Experimental: ARCR augmented with REGENETEN™ Bioinductive Implant
    • During the ARCR procedure, the REGENETEN™ Bioinductive Implant is covering the tendon and attached to the bone and the tendon with small anchors.
  • Sham Comparator: ARCR alone
    • The rotator cuff is repaired during arthoscopic standard procedure. No product is added for healing
  • Other: ARCR revision group
    • ARCR revision group allows treatment of subjects having recurrent tears, ARCR supplemented with REGENETEN

Clinical Trial Outcome Measures

Primary Measures

  • 6 months retear rate
    • Time Frame: 6 months post surgery
    • 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).

Secondary Measures

  • Retear rate
    • Time Frame: 3, 12, and 24 months
    • Cumulative 3, 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).
  • Oxford Shoulder Score (OSS)
    • Time Frame: 3, 6, 12 and 24 months
    • 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.
  • Western Ontario Rotator Cuff (WORC)/Chinese version WORC (C-WORC) Index)
    • Time Frame: 3, 6, 12 and 24 months
    • 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).
  • Constant-Murley Score
    • Time Frame: 6, 12 and 24 months
    • 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.
  • Subjective shoulder value (SSV)
    • Time Frame: 3, 6, 12 and 24 months
    • 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).
  • EuroQol 5 Dimension 5 Level (EQ-5D-5L) Score
    • Time Frame: 3, 6, 12 and 24 months
    • 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.
  • Patient satisfaction Questionnaire Outcome
    • Time Frame: 3, 6, 12 and 24 months
    • 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.
  • Pain, Visual analog scale (VAS) Score
    • Time Frame: 2 weeks, 6 weeks, 3, 6, 12 and 24 months
    • 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
  • MRI Tendon Findings in ARCR augmented with REGENETEN versus ARCR alone via Sugaya Score postoperatively
    • Time Frame: 3, 6, 12 and 24 months
    • 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.
  • MRI Tendon Findings in ARCR augmented with REGENETEN versus ARCR alone via Goutallier Classification postoperatively
    • Time Frame: 3, 6, 12 and 24 months
    • 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.
  • Total tendon thickness, tendon length will be assessed by MRI Tendon Findings in ARCR augmented with REGENETEN versus ARCR alone postoperatively
    • Time Frame: 3, 6, 12 and 24 months
    • Tendon thickness, length will be assessed by MRI
  • Retear: Divided into symptomatic and asymptomatic postoperatively
    • Time Frame: 3, 6, 12 and 24 months
    • Retear will be divided into symptomatic and asymptomatic based on MRI Tendon Findings in ARCR augmented with REGENETEN versus ARCR alone.
  • Size of retear: anteroposterior [AP]/mediolateral [ML]) postoperatively
    • Time Frame: 3, 6, 12 and 24 months
    • Size of retear will be based on MRI Tendon Findings in ARCR augmented with REGENETEN versus ARCR alone.
  • Shape of retear postoperatively
    • Time Frame: 3, 6, 12 and 24 months
    • Shape of retear will be based on MRI Tendon Findings in ARCR augmented with REGENETEN versus ARCR alone
  • Outcome of Return to Work Questionnaire in ARCR augmented with REGENETEN versus ARCR alone
    • Time Frame: 2 weeks, 6 weeks, 3, 6, 12 and 24 months
    • Generic questionnaire, covering work related questions,including demographics on laborer/sedentary.
  • Cumulative duration of opioid use in ARCR augmented with REGENETEN versus ARCR alone
    • Time Frame: 2 weeks
    • 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 .
  • Total operative time ARCR augmented with REGENETEN versus ARCR alone
    • Time Frame: Intra-operative time
    • Total operative time ARCR augmented with REGENETEN versus ARCR alone.
  • Sling type and mobilization time in ARCR augmented with REGENETEN versus ARCR alone
    • Time Frame: 2 weeks
    • 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.

Participating in This Clinical Trial

Inclusion Criteria

1. Subject requires Arthroscopic rotator cuff repair (ARCR);

2. Subjects with a diagnosis of a symptomatic primary or recurrent (revision repair subject group), large or massive tear (≥ 3 cm AP/ML as measured on MRI and confirmed on arthroscopy using a calibrated probe) of the supraspinatus and/or infraspinatus tendons amenable to repair;

3. Subject is > 40 years of age (no upper limit);

4. Subject provides written informed consent for study participation using an Independent Ethical Committee (IEC) / Institutional Review Board (IRB) approved consent form;

5. Subject is willing and able to participate in required follow-up visits and is able to complete study activities.

Exclusion Criteria

1. Subjects who are unable to tolerate magnetic resonance imaging (MRI), due to psychiatric or medical contraindications;

2. Subjects with Samilson-Prieto osteoarthritis > 2;

3. Subjects with current or prior infection of the ipsilateral shoulder;

4. Subjects with known hypersensitivity to bovine-derived materials;

5. Subjects with known inflammatory arthropathy, history of inflammatory arthropathy, or chronic joint disease;

6. Subjects with prior shoulder surgery (not including rotator cuff repair [revision repair subject group only], biceps tenodesis/tenotomy, distal clavicle excision [DCE], subacromial decompression);

7. Subjects with an irreparable or partially reparable rotator cuff tear;

8. Subjects with a subscapularis tear requiring repair;

9. Subjects requiring a concomitant labral fixation procedure;

10. Subjects requiring a concomitant os acromiale fixation procedure;

11. Subjects with glenohumeral joint instability (multiple dislocations/subluxations);

12. Subjects with a subacromial or intra-articular injection within 3 months prior to surgery;

13. 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;

14. Subject is pregnant or breast feeding;

15. Subjects who are currently involved in any injury litigation relating to the index shoulder;

16. Subjects who are enrolled, or plan to enroll, in another clinical trial during this study that would affect the outcomes of this study;

17. Subjects with a history of noncompliance with medical treatment, physical therapy (PT)/rehabilitation, or clinical study participation

18. 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;

19. Subjects who do not meet the indication or are contraindicated according to specific Smith+Nephew REGENETEN System's Instructions for Use (IFUs);

20. Subject that meets the definition of a Vulnerable Subject per ISO14155:2011 Section 3.44.

Gender Eligibility: All

Minimum Age: 40 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Smith & Nephew, Inc.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Chris Peach, MBBS MD FRCS (Tr&Orth), Principal Investigator, Manchester University NHS Foundation Trust
  • Overall Contact(s)
    • Isabelle Arrighi, + 41 (0) 79 1234 043, Isabelle.arrighi@smith-nephew.com

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