REGENETEN™ Bioinductive Implant System in Full-thickness Tears

Not Applicable

Terminated

Conditions: Rotator Cuff Injuries

Interventions: Procedure: Arthroscopic rotator cuff repair
Device: Arthroscopic rotator cuff repair with REGENETEN™ Bioinductive Implant augmentation
Device: Arthroscopic rotator cuff repair for revision surgery

Registration Number: NCT04450342

Lead Sponsor: Smith & Nephew, Inc.

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 119

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ARCR alone	Arthroscopic rotator cuff repair	The rotator cuff is repaired during arthroscopic standard procedure. No product is added for healing
ARCR augmented with REGENETEN™ Bioinductive Implant	Arthroscopic rotator cuff repair with REGENETEN™ Bioinductive Implant augmentation	During the ARCR procedure, the REGENETEN™ Bioinductive Implant is covering the tendon and attached to the bone and the tendon with small anchors.
ARCR revision group	Arthroscopic rotator cuff repair for revision surgery	ARCR revision group allows treatment of subjects having recurrent tears, ARCR supplemented with REGENETEN

Primary Outcome Measures

Name	Time	Method
Retear Rate at 6 Months	6 months	Retear rate was measured by the percentage of retears 6 months after full-thickness arthroscopic rotator cuff repair (ARCR) surgery. Retear was defined as Sugaya Type IV or V retear/recurrence (full-thickness discontinuity seen on both coronal and oblique sagittal MRI images).

Secondary Outcome Measures

Name	Time	Method
Size of Retear: Mediolateral (ML) Length	Day 0, 3 months and 6 months	Mediolateral (ML) length of retear in millimeters (mm) at operation day (Day 0), 3 months, and 6 months taken from magnetic resonance imaging (MRI).
Shape of Retear: Operative Visit	Day 0	Shape of tear at operative visit (Day 0) from magnetic resonance imaging (MRI) for those with re-tear at 6 months. Participants were categorized as one of the following tear shapes: * Crescent * L Shape * Reverse L * U Shape * Massive/Contracted * Unable to Determine
Number of Retears at 3 Months, 12 Months, and 24 Months	3 months, 12 months, and 24 months	Number of participants with retears present 3 months, 12 months, and 24 months after full-thickness arthroscopic rotator cuff repair (ARCR) surgery. Retear was 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)	Baseline, 3 months, 6 months, 12 months 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	Baseline, 3 months, 6 months, 12 months 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). Scores range from 0 to 2100 with 0 indicating no symptoms at all and 2100 indicating the worst possible symptoms (i.e., a lower score is a better outcome).
Constant-Murley Score	Baseline, 3 months, 6 months, 12 months 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, activities of daily living, strength, and range of motion - forward flexion, external rotation, abduction and internal rotation of the shoulder. Scores range from 0 to 100 with a higher score indicating better shoulder function (i.e., a high score is a better outcome).
Subjective Shoulder Value (SSV)	Baseline, 3 months, 6 months, 12 months and 24 months	The Subjective Shoulder Value (SSV) is defined as a patient's subjective shoulder assessment expressed as a percentage of an entirely normal shoulder. The SSV ranges from 0 to 100, with a higher score indicating a better outcome.
EuroQol 5 Dimension 5 Level (EQ-5D-5L) Index Score	Baseline, 3 months, 6 months, 12 months 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 participant's health state and consists of five dimensions to create an index score for 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 participant is asked to indicate his/her health state by marking the most appropriate statement in each of the five areas. The index score ranges from 0 to 1, with a higher score indicating a better outcome.
EuroQol 5 Dimension 5 Level (EQ-5D-5L) Visual Analog Scale (VAS) Score	Baseline, 3 months, 6 months, 12 months and 24 months	The EQ-5D-5L score consists of two parts: a descriptive system and a visual analogue scale (VAS). The VAS score is the participant's self-rated health on a vertical visual analogue scale that ranges from 0 to 100 with 100 representing the best health imaginable and 0 indicating the worst (i.e., a higher score is a better outcome).
Patient Satisfaction Questionnaire: Medical Care	Baseline, 3 months, 6 months, 12 months and 24 months	The Patient Satisfaction Questionnaire was a simple subjective assessment from the patient's perspective for the question "How satisfied are you with your medical care?". Scores ranged from 0 to 100 with 0 indicating the least satisfied and 100 indicating the most satisfied.
Size of Retear: Anteroposterior (AP) Length	Day 0, 3 months and 6 months	Anteroposterior (AP) length of retear in millimeters (mm) at operation day (Day 0), 3 months, and 6 months taken from magnetic resonance imaging (MRI).
Patient Satisfaction Questionnaire: How Well Did the Surgery Relieve the Pain	3 months, 6 months, 12 months and 24 months	The post-operative Patient Satisfaction Questionnaire for pain relief was a simple subjective assessment from the patient's perspective at 3, 6, 12, and 24 months. Participants were asked to answer, "How well did the surgery relieve the pain?" with one of the following responses: * Excellent * Very Good * Good * Fair * Poor
Patient Satisfaction Questionnaire: How Well Did the Surgery Improve Your Ability to Perform Regular Activities	3 months, 6 months, 12 months and 24 months	The post-operative Patient Satisfaction Questionnaire for ability to perform regular activities was a simple subjective assessment from the patient's perspective at 3, 6, 12, and 24 months. Participants were asked to answer, "How well did the surgery improve your ability to perform regular activities?" with one of the following responses: * Excellent * Very Good * Good * Fair * Poor
Patient Satisfaction Questionnaire: How Well Did the Surgery Allow You to Perform Heavy Work or Sport Activities	3 months, 6 months, 12 months and 24 months	The post-operative Patient Satisfaction Questionnaire for performing heavy work or sport activities was a simple subjective assessment from the patient's perspective at 3, 6, 12, and 24 months. Participants were asked to answer, "How well did the surgery allow you to perform heavy work or sport activities?" with one of the following responses: * Excellent * Very Good * Good * Fair * Poor
Patient Satisfaction Questionnaire: How Well Did the Surgery Meet Your Expectations	3 months, 6 months, 12 months and 24 months	The post-operative Patient Satisfaction Questionnaire for surgery expectations was a simple subjective assessment from the patient's perspective at 3, 6, 12, and 24 months. Participants were asked to answer, "How well did the surgery meet your expectations?" with one of the following responses: * Excellent * Very Good * Good * Fair * Poor
Patient Satisfaction Questionnaire: Would You Have the Operation Again if Needed on Another Joint	3 months, 6 months, 12 months and 24 months	The post-operative Patient Satisfaction Questionnaire for having the operation again on another joint was a simple subjective assessment from the patient's perspective at 3, 6, 12, and 24 months. Participants were asked to answer, "Would you repeat the operation again if needed on another joint?" with one of the following responses: * Definitely Yes * Probably Yes * Possibly Not * Definitely Not
Pain - Visual Analog Scale (VAS) Score	2 weeks, 6 weeks, 3 months and 6 months	Pain was measured using a 100-point Visual Analog Scale (VAS) score with a range from 0 to 100 where zero (0) represented no pain and 100 represented the worst pain imaginable (i.e., a lower score was a better outcome).
MRI Tendon Findings: Supraspinatus Sugaya Score	3 months, 6 months, 12 months and 24 months	The Sugaya Score was used to determine postoperative cuff integrity of the supraspinatus tendon through magnetic resonance imaging (MRI). Participants were classified as Type I, Type II, Type III, Type IV, Type V, or Indeterminate. Type I indicated 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: Infraspinatus Sugaya Score	3 months, 6 months, 12 months and 24 months	The Sugaya Score was used to determine postoperative cuff integrity of the infraspinatus tendon through magnetic resonance imaging (MRI). Participants were classified as Type I, Type II, Type III, Type IV, Type V, or Indeterminate. Type I indicated 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: Supraspinatus Goutallier Classification	3 months, 6 months, 12 months and 24 months	Goutallier grading for the supraspinatus tendon was used to classify the fatty infiltration of the rotator cuff. The Goutallier classification ranged from Grade 0 to Grade 4. Grade 0 indicated a completely normal muscle without any fatty streaks. Grade I indicated some fatty streaks. Grade 2 indicated increased fatty infiltration, but more muscle than fat. Grade 3 indicated equal amounts of fat and muscle. Grade 4 indicated more fat than muscle was present. Participants were classified as one of the following: * Grade 0 * Grade I * Grade 2 * Grade 3 * Grade 4 * Unable to assess
MRI Tendon Findings: Infraspinatus Goutallier Classification	3 months, 6 months, 12 months and 24 months	Goutallier grading for the infraspinatus tendon was used to classify the fatty infiltration of the rotator cuff. The Goutallier classification ranged from Grade 0 to Grade 4. Grade 0 indicated a completely normal muscle without any fatty streaks. Grade I indicated some fatty streaks. Grade 2 indicated increased fatty infiltration, but more muscle than fat. Grade 3 indicated equal amounts of fat and muscle. Grade 4 indicated more fat than muscle was present. Participants were classified as one of the following: * Grade 0 * Grade I * Grade 2 * Grade 3 * Grade 4 * Unable to assess
Total Tendon Thickness	3 months, 6 months, 12 months and 24 months	Post-operative tendon thickness in millimeters (mm) taken from magnetic resonance imaging (MRI).
Total Tendon Length	3 months, 6 months, 12 months and 24 months	Post-operative tendon length in millimeters (mm) taken from magnetic resonance imaging (MRI).
Size of Retear: Area (Anteroposterior [AP] / Mediolateral [ML])	Day 0, 3 months and 6 months	Area of retear in millimeters squared (mm\^2) at operation day (Day 0), 3 months, and 6 months taken from magnetic resonance imaging (MRI).
Shape of Retear: 3 Months, 6 Months, 12 Months, and 24 Months	3 months, 6 months, 12 months and 24 months	Shape of retear post-operatively at 3 months, 6 months, 12 months and 24 months from magnetic resonance imaging (MRI). Participants were categorized as one of the following retear shapes: * Intact (i.e., no re-tear) * Crescent * Longitudinal * Massive * Unable to Determine
Return to Work Questionnaire	2 weeks, 6 weeks, 3 months and 6 months	Generic questionnaire at 2 weeks, 6 weeks, 3 months, and 6 months with Yes/No responses for the following questions: * Returned to work? * Have you been able to return to the job you did before your surgery? * Did you feel ready to go back to work physically? * Since returning to work, any time off due to shoulder pain or weakness? * Since last follow-up visit did you take additional time off due to shoulder pain/weakness?
Return to Work Questionnaire: Reason for Not Getting Back to Work	2 weeks, 6 weeks, 3 months, 6 months	The reason for not getting back to work was a conditional question asked from the Return to Work Questionnaire. Only participants with a 'No' response to the "Returned to work?" question were asked to provide a reason for not getting back to work from one of the following options: * Physical capability * Safety * Motivation * Other
Return to Work Questionnaire: Reason Couldn't Return to Activities	2 weeks, 6 weeks, 3 months, 6 months	The reason for not returning to the same activities was a conditional question asked from the Return to Work Questionnaire. Only participants with a 'No' response to the "Have you been able to return to the job you did before your surgery?" question were asked to provide a reason for not getting back to work from one of the following options: * Physical capability * Safety * Motivation * Other
Return to Work Questionnaire: Time Off	2 weeks, 6 weeks, 3 months, 6 months	Number of days taken off after returning to work because of shoulder pain or weakness was a conditional question asked from the Return to Work Questionnaire. Only participants with a 'Yes' response to the "Since returning to work, any time off due to shoulder pain or weakness?" question were asked to provide how long they have taken off in days.
Return to Work Questionnaire: Duration Away From Work (Days)	2 weeks, 6 weeks, 3 months, 6 months	Number of days taken away from work following surgery was a conditional question asked from the Return to Work Questionnaire. Only participants with a 'Yes' response to the "Returned to work?" question were asked to provide the number of days taken away from work
Duration of Opioid Use	Following surgery, up to 14 days	Duration of opioid use in days up to 14 days post-surgery was based on self-reported opioid use diary completed by the patient on a daily basis for 2 weeks after surgery.
Opioid Use for More Than 5 Days Post-Surgery	Following surgery, up to 14 days	Number of participants taking opioids for more than 5 days post-surgery (Yes/No) was based on self-reported opioid use diary completed by the patient on a daily basis for 2 weeks after surgery.
Total Operative Time	Intraoperative	Total operative time in minutes.
Sling Type	up to 3 months	The type of sling used up to 3 months post-surgery for each participant was categorized as one of the following: * Standard Sling * Shoulder Immobilizer * Sling and Swathe * Abduction Sling * External Rotation Sling * Other * Missing
Mobilization Time in Sling	up to 3 months	Mobilization time was the duration, measured in weeks, that participants spent in a sling.

Trial Locations

Locations (30): Balgrist University Hospital
🇨🇭
Zurich, Switzerland
Women's College Hospital Toronto
🇨🇦
Toronto, Ontario, Canada
Saint John Orthopaedics
🇨🇦
Saint John, New Brunswick, Canada
University Hospital of South Manchester NHS Foundation Trust
🇬🇧
Wythenshawe, Manchester, United Kingdom
Hôpital Privé de l'Ouest Parisien
🇫🇷
Trappes, Île-de-France, France
Hôpital Ambroise Paré
🇫🇷
Paris, Boulogne-Billancourt, France
Harbin Clinic
🇺🇸
Rome, Georgia, United States
Cleveland Clinic
🇺🇸
Cleveland, Ohio, United States
Syracuse Orthopedic Specialists
🇺🇸
DeWitt, New York, United States
Sinai Hospital
🇺🇸
Baltimore, Maryland, United States
Rush University Medical Center
🇺🇸
Chicago, Illinois, United States
Houston Methodist The Woodlands
🇺🇸
The Woodlands, Texas, United States
Macquarie University Hospital
🇦🇺
Sydney, New South Wales, Australia
Texas Orthopedic Specialists
🇺🇸
Bedford, Texas, United States
McMaster University
🇨🇦
Hamilton, Ontario, Canada
Prince of Wales Hospital
🇭🇰
Hong Kong, Hong Kong
Bichat Hospital
🇫🇷
Paris, France
Clinique Saint-Jean - Montpellier
🇫🇷
Montpellier, France
Hôpital Pasteur 2
🇫🇷
Nice, Provence-Alpes-Côte d'Azur, France
Singapore General Hospital
🇸🇬
Singapore, Singapore
Schulthess Klinik
🇨🇭
Zurich, Switzerland
Royal Blackburn Hospital
🇬🇧
Blackburn, Lancashire, United Kingdom
Royal National Orthopaedic Hospital NHS Trust
🇬🇧
Stanmore, Middlesex, United Kingdom
Nottingham University Hospital
🇬🇧
Nottingham, Nottinghamshire, United Kingdom
University Hospitals Coventry and Warwickshire
🇬🇧
Coventry, Warwickshire, United Kingdom
Southmead Hospital
🇬🇧
Bristol, United Kingdom
The Royal Orthopaedic Hospital NHS Foundation Trust
🇬🇧
Birmingham, West Midlands, United Kingdom
Ashland Memorial Medical Center
🇺🇸
Ashland, Wisconsin, United States
OrthoSport Victoria
🇦🇺
Richmond, Victoria, Australia
Liverpool University Hospitals NHS Foundation Trust
🇬🇧
Liverpool, Merseyside, United Kingdom