LifeNet: Extracellular Matrix Graft in Rotator Cuff Repair

Study Overview
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Brief Summary
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This trial is to evaluate the effectiveness of the ArthroFLEX® ECM scaffold graph as an augment in rotator cuff repair surgery to reduce the failure rate of rotator cuff repairs for large and massive rotator cuff tears.

Detailed Description
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This is a prospective, randomized, controlled, multi-center clinical trial to evaluate the effectiveness of an ECM scaffold graft to augment repair of a large/massive rotator cuff tear. The study will involve 70 patients. 35 patients will be randomly assigned to each arm of the study. Despite advances in surgical technology, repairs of large (3-5 cm) and massive (>5 cm) rotator cuff tears (RCT) fail between 20%-90% of the time [1]. Due to their size and increased structural involvement, large or massive RCT present a substantial challenge to orthopaedic surgeons. [16] The repairs tend to fail at the suture-tendon junction, which is due to several factors, including tension at the repair and quality of the tendon [1-2,5]. Full thickness tears are uncommon in younger patients, especially those less than forty years old and are usually traumatic in etiology. Younger patients also typically fair better following arthroscopic rotator cuff repair with fewer failures and more successful return to pre-injury level of function [16]. One strategy to augment repair of large to massive rotator cuff tears has been the development of biological scaffold materials, which are composed of extracellular matrix (ECM). The ECM composing the scaffolds are made from a number of tissues, including, but not limited to, small intestinal submucosa (SIS), dermis, and pericardium [3]. Studies to date include both prospective and retrospective in animal and human models, and include Restore, a porcine-derived SIS by DePuy Orthopaedics, GraftJacket, a human-derived, non-cross-linked dermis graft by Wright Medical Technology, and Zimmer Collagen Repair, a cross-linked porcine derived dermal graft made by Zimmer. Restore studies have shown no benefit and some even an increase in repair failure with recommendations not to use to augment repair. GraftJacket studies have shown a reduction in graft failure; however, several of the Restore and GraftJacket studies are limited by a lack of a control cohort. The Zimmer graft studies have conflicting results with both an improvement and no improvement in failure rates of repair. The prior studies listed are all in vivo; however, the majority are not randomized trials and thus do not have a control with which to compare data. In addition, some trials include open repairs. A lack of prospective, randomized, controlled, in vivo trials exist that evaluate the ability of the ECM scaffold graft augmentation in large to massive arthroscopic rotator cuff repairs to decrease the failure rate.

Official Title
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Extracellular Matrix Scaffold Graft Augmentation in Rotator Cuff Repair: a Prospective, Randomized, Controlled Trial

Conditions
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Rotator Cuff Tear

Intervention / Treatment
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* Biological: ArthroFLEX ECM scaffold graft
* Procedure: Control
* Biological: Crossover


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a large (3-5 cm) to massive (>5 cm) rotator cuff tear who will be undergoing open or arthroscopic repair. The cuff tear size will be determined on pre-operative MRI and US. Patients who are willing and able to provide written informed consent for their involvement in the study. Patients who meet criteria for RCR surgery Patients older than 18 years of age Exclusion Criteria: Patients with addiction to illegal drugs, solvents or alcohol who are actively using or have previously attempted and failed a treatment program. Patients with bacteremia, a systemic infection, or infection of the surgical site. All those who are prisoners. Patients who are pregnant or nursing. All those with a condition that may limit a patient's ability to finalize the study or that may cause an undue risk to the patient's health and well-being.

Ages Eligible for Study
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Minimum Age: 18 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control Group<br>Patients randomly assigned into the control group will undergo open or arthroscopic rotator cuff repair using the surgeon's standard practice. No ECM graft will be used. | |
| Active Comparator: Treatment Group<br>Patients randomly assigned into the treatment group will undergo open or arthroscopic rotator cuff repair and the surgeon will use the ArthroFLEX® ECM graft to augment the repair. ECM scaffold grafts are indicated for the reinforcement of soft tissues repaired by sutures or suture anchors during tendon repair surgery, including rotator cuff. | Biological: ArthroFLEX ECM scaffold graft<br>* In patients receiving a graft, thru mini open technique the lateral portal incision will be extended vertically approximately 5-6 cm. A standard, deltoid-splitting, mini-open approach will then be performed, leaving the deltoid attachment to the acromion intact. For arthroscopic technique same method of fixation will be used below. The dermis graft will be sized and cut so as to cover the entire repair site in both medial-lateral and anterior-posterior dimensions.<br>Procedure: Control<br>* This group will undergo rotator cuff repair surgery, but will not receive the ECM scaffold graft.<br>* Other names: Surgery - no graft;|
| Other: Crossover Group<br>Patients initially randomized to the control arm who cannot be repaired without an augmented graft will be followed for safety and remain in the study and put into a group for the intention to treat. | Procedure: Control<br>* This group will undergo rotator cuff repair surgery, but will not receive the ECM scaffold graft.<br>* Other names: Surgery - no graft;Biological: Crossover<br>* Patients randomized to the control arm who cannot be repaired without an augmented graft will be followed for safety and remain in the study and put into a group for the intention to treat.<br>* Other names: Surgery - graft if necessary for repair;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tendon healing | Success as defined by tendon healing after rotator cuff repair, as indicated based on MRI. | As assessed 1 year postoperatively. | 
| Comparison of healing by MRI vs US | Comparison of tendon healing will be assessed using US imaging modalities versus MRI. | As assessed 1 year postoperatively. | 
| Progress of tendon healing | Progress of tendon healing based on US will be used as predictive data for 1 year success (based on primary outcome) | As assessed at 1 year postoperatively. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Outcomes: The American Shoulder and Elbow Surgeon Shoulder Score (ASES) | The ASES is standardized form for assessment of the shoulder. There are patient-self-evaluation and physician assessment sections. The patient self-evaluation section form contains visual analog scales for pain and instability and an activities of daily living questionnaire. The activities of daily living questionnaire is marked on a four-point ordinal scale that can be converted to a cumulative activities of daily living index. The physician assessment section assesses range of motion, specific physical signs, strength, and stability. A shoulder score can be derived from the visual analogue scale score for pain (50%) and the cumulative activities of daily living score (50%). | Through study completion (1 year after surgery). Specifically this assessment will be administered one time before surgery (during the preoperative examination) and then at every follow-up visit thereafter (6 wks, 3 mos, 6 mos, and 1 year after surgery). | 
| Patient Outcomes: The Western Ontario Rotator Cuff Index (WORC) | A disease-specific quality of life measurement tool for patients with rotator cuff disease. Patients will respond to by marking a scale with ranges between none and extreme. Information collected includes physical symptoms, such as pain and weakness levels in the shoulder, the impact of the patient's shoulder injury on their sports/recreational activities, work (inside or outside of the home), lifestyle/activities of daily living (ADL), and its emotional impact, such as frustration level, depression, and any worry/concern a patient might be about how their injury might affect their occupation. | Through study completion (1 year after surgery). Specifically this assessment will be administered one time before surgery (during the preoperative examination) and then at every follow-up visit thereafter (6 wks, 3 mos, 6 mos, and 1 year after surgery). | 
| Patient Outcomes: Measurement of Shoulder Activity Level | This activity scale was developed using established principles: item generation, item reduction, pretesting, and reliability and validity testing. The activity rating is a numerical sum of scores for five activities rated on a five-point frequency scale from never performed (0 points) to daily (4 points). Patients were scored on the following criteria: carrying an object 8 lb or heavier by hand, handling objects overhead, weight training with arms, swinging motion (ie, hitting tennis or golf ball), and lifting objects 25 lb or heavier. Two additional multiple choice questions provide a score assessing participation in contact and overhead sports. It can be used in conjunction with patient-based measures of shoulder outcome to define patient populations for cohort studies, and to assess activity level as a prognostic factor in patients with shoulder disorders. (Clin Orthop Relat Res. 2005 Oct;439:101-8.) | Through study completion (1 year after surgery). Specifically this assessment will be administered one time before surgery (during the preoperative examination) and then at every follow-up visit thereafter (6 wks, 3 mos, 6 mos, and 1 year after surgery). | 
| Patient Outcomes: 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%. (J Shoulder Elbow Surg. 2007 Nov-Dec;16(6):717-21.) | Through study completion (1 year after surgery). Specifically this assessment will be administered one time before surgery (during the preoperative examination) and then at every follow-up visit thereafter (6 wks, 3 mos, 6 mos, and 1 year after surgery). | 
| Patient Outcomes: Constant Score (CS) | C Constant and A Murley. This scoring system consists of four variables that are used to assess the function of the shoulder. The right and left shoulders are assessed separately. The subjective variables are pain and ADL (sleep, work, recreation / sport) which give a total of 35 points. The objective variables are range of motion and strength which give a total of 65 points. More information on the Constant Score can be found here: https://www.shoulderdoc.co.uk/article/9. | Through study completion (1 year after surgery). Specifically this assessment will be administered one time before surgery (during the preoperative examination) and then at every follow-up visit thereafter (6 wks, 3 mos, 6 mos, and 1 year after surgery). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rotator Cuff Tear, Large Rotator Cuff Tear, Massive Rotator Cuff Tear, ECM, Extracellular Matrix, ArthroFLEX