Efficacy of an Amniotic Fluid Derived Allograft, (FlōGraft®) in Rotator Cuff Repairs: A Prospective Study

A Prospective, Randomized Study Comparing Outcomes Following Arthroscopic Double-row Rotator Cuff Repair With and Without the Addition of a Cryopreserved, Liquid, Injectable Amnion Allograft

Rotator Cuff (RC) repair will be augmented with the injection of a human amniotic fluid derived allograft at the repair interface junction. A secondary injection will be administered at the time of repair in the supraspinatus muscle body medial to the musculotendonous junction.

Study Overview

• Status: Unknown
• Conditions: Rotator Cuff Tear; Fatty Atrophy
• Intervention / Treatment: Biological: Superiority of augmented repairs; Biological: Fat degeneration of supraspinatus muscle

Detailed Description

Patients will be given a written explanation of the study and screened for inclusion and exclusion criteria. Included patients will have a repairable, full thickness rotator cuff tear limited to the supraspinatus and infraspinatus, confirmed by MRI. Patients with concomitant biceps tenotomy, tenodesis, arthroscopic subacromial decompression, and distal clavicle excision will be included. Patients with prior operations on the shoulder, partial thickness tears, subscapularis tears or labral tears requiring repair, irreparable supraspinatus tears, staged bilateral rotator cuff repairs, or concomitant suprascapular nerve decompression will be excluded. We will also exclude patients with co-morbid conditions requiring the use of corticosteroids. Patients who cannot have an MRI for medical reasons will also be excluded.

All participants will volunteer to enroll in the study by signing informed consent (Attachment B). All potential subjects will be over 18 years of age and capable of providing their own informed consent. Patients will be recruited from the patient populations of Dr. Edwards, Dr. Elkousy, Dr. Morris, Dr. Gombera and Dr Brown. The informed consent process will be conducted by the investigators, their staff, or their research associates (e.g., orthopedic surgery fellows), who will explain the purpose and methods of the study, the risks and benefits, and requirements of participation. Randomization to groups will occur following informed consent; patients will not know to which group they are assigned.

1. Arthroscopic transosseous equivalent rotator cuff (TOE) repair will be performed; this is our standard procedure, using suture anchors in the medial and lateral rows for a TOE technique. The medial row will be 4.5 mm Polyether ether ketone (PEEK) anchors and the lateral row will be a 5.5 mm PEEK knotless anchor. Medial row anchor sutures will be tied.
2. FlōGraft® details: 4cc of FlōGraft® will be used in each treated patient, provided in a single peel pouch containing two 2cc vials. In FlōGraft® treated patients, FlōGraft® will be applied, following repair as detailed below.

3. FlōGraft® Preparation Protocol 3.1 Store FlōGraft® at -65◦C or colder until immediately prior to use. 3.2 Remove box from cold storage, open exterior box and remove interior package containing vials.

   3.3 Neither the interior dust cover nor the outside of the vial are sterile. Do not place either the interior package or the vial in sterile field.

   3.4 Remove vials from packaging, place on non-sterile, secure, flat surface, or hold vial firmly in one hand allowing contents to thaw (3-7 minutes.) Hold vial upright to aspirate contents. Note: Allograft should be implanted immediately post-thaw, but not later than eight (8) minutes post-thaw.

   3.5 Pierce the vial cap and draw thawed solution into syringe. Do not pressurize vial with air prior to extracting thawed FlōGraft® solution.

   3.6 If needed, change needle size based on surgeon preference (18g to 23g.)

4. FlōGraft® Implantation 4.1 After the rotator cuff repair is completed, shut off water-flow to joint. Excess water in joint is drained through the skin incisions, creating a "dry" sub-acromial space.

   4.2 Insert needle through skin incision or percutaneously. Under direct visualization, inject FlōGraft® directly into rotator cuff tissue at repair site in approximately 0.50 cc aliquots. Cover entire repair site.

   4.3 Implant allograft into the cuff muscle more medially to the repair in 0.25-0.5 cc aliquots, as appropriate.

5. Postoperative management: 4 weeks immobilization in abduction sling; passive range of motion will be initiated at the discretion of the surgeon based on tear size. Active range of motion will begin at 8 weeks to 16 weeks.
6. Diagnostic MRI will be performed at one and two years postoperatively.

• Study Type: Interventional
• Enrollment (Anticipated): 260
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Texas Orthopedic Hospital
      • Contact: Dede Wilson; Phone Number: 713-799-8600; Email: dede.wilson@hcahealthcare.com
      • Principal Investigator: Hussein Elkousy, MD
      • Principal Investigator: Bradley Edwards, MD
      • Sub-Investigator: Brent Morris, MD
      • Sub-Investigator: Mufaddal M Gombera, MD
      • Sub-Investigator: Barrett S Brown, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Included patients will have a repairable, full thickness rotator cuff tear limited to the supraspinatus and infraspinatus, confirmed by MRI. Patients with concomitant biceps tenotomy, tenodesis, arthroscopic subacromial decompression, and distal clavicle excision will be included.

Exclusion Criteria:

• Patients with prior operations on the shoulder, partial thickness tears, subscapularis tears or labral tears requiring repair, irreparable supraspinatus tears, staged bilateral rotator cuff repairs, or concomitant suprascapular nerve decompression will be excluded. We will also exclude patients with co-morbid conditions requiring the use of corticosteroids. Patients who cannot have an MRI for medical reasons will also be excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Superiority of augmented repairs; Assess pain, function, and structural integrity of the rotator cuff at 3 months, 6 months, 1 year, and 2 years post-operation	Biological: Superiority of augmented repairs; 4cc of FlōGraft® injected into repair subject tissue divided evenly between repair site and muscle body; Other Names: FlōGraft®; Human amniotic fluid-derived allograft; Biological: Fat degeneration of supraspinatus muscle; 4cc of FlōGraft® injected into repair subject tissue divided evenly between repair site and muscle body; Other Names: FlōGraft®; Human amniotic fluid-derived allograft
ACTIVE_COMPARATOR: Fat degeneration of supraspinatus muscle; MRI assessment the quantity and disposition of fat within the supraspinatus muscle body compared to pre-operation MRI, at 1 year and 2 years post-operation	Biological: Superiority of augmented repairs; 4cc of FlōGraft® injected into repair subject tissue divided evenly between repair site and muscle body; Other Names: FlōGraft®; Human amniotic fluid-derived allograft; Biological: Fat degeneration of supraspinatus muscle; 4cc of FlōGraft® injected into repair subject tissue divided evenly between repair site and muscle body; Other Names: FlōGraft®; Human amniotic fluid-derived allograft

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Structural healing integrity	Improved structural healing is the best indication of long-term surgery success. The Sugaya grading system is a method to account for structural integrity of the rotator cuff following surgery with five possible classifications. Sugaya scale: type I indicating sufficient thickness with homogeneously low intensity; type II, sufficient thickness with partial high intensity; type III, insufficient thickness without discontinuity; type IV, the presence of a minor discontinuity; and type V, the presence of a major discontinuity. Types I-III indicate different levels of healing. The classification of each shoulder must be assessed using MRIs (grade determined by a blinded musculoskeletal radiologist).	1 year post-operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fatty degeneration	Musculoskeletal radiologists will also evaluate fatty degeneration of the rotator cuff at 1 year post-operatively from the MRI using the Global Fatty Degeneration Index (GFDI).	1 year post-operation
Structural healing integrity (2)	Improved structural healing is the best indication of long-term surgery success. The Sugaya grading system is a method to account for structural integrity of the rotator cuff following surgery with five possible classifications. Sugaya scale: type I indicating sufficient thickness with homogeneously low intensity; type II, sufficient thickness with partial high intensity; type III, insufficient thickness without discontinuity; type IV, the presence of a minor discontinuity; and type V, the presence of a major discontinuity. Types I-III indicate different levels of healing. The classification of each shoulder must be assessed using MRIs (grade determined by a blinded musculoskeletal radiologist).	2 years post-operation
Fatty degeneration (2)	Musculoskeletal radiologists will also evaluate fatty degeneration of the rotator cuff at 2 years post-operatively from the MRI using the Global Fatty Degeneration Index (GFDI).	2 years post-operation
Functional outcome	Functional outcomes will be assessed using the American Shoulder and Elbow Surgeons Score.	Baseline
Functional outcome (2)	Functional outcomes will be assessed using the American Shoulder and Elbow Surgeons Score.	3 months post-operation
Functional outcome (3)	Functional outcomes will be assessed using the American Shoulder and Elbow Surgeons Score.	6 months post-operation
Clinically Assessed Re-tear	Any incidence of clinically assessed re-tear will be documented by the treating surgeon during routine postoperative follow-up clinic visits and examinations.	3 months post-operation
Clinically Assessed Re-tear (2)	Any incidence of clinically assessed re-tear will be documented by the treating surgeon during routine postoperative follow-up clinic visits and examinations.	6 months post-operation

Collaborators and Investigators

• Sponsor: Applied Biologics, LLC
• Collaborators: Fondren Orthopedic Group L.L.P.; Texas Orthopedic Hospital
• Investigators: Study Chair: Gregory Stocks, MD, Texas Orthopedic Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 24, 2017
• Primary Completion (ANTICIPATED): September 30, 2019
• Study Completion (ANTICIPATED): September 30, 2019

Study Registration Dates

• First Submitted: November 20, 2017
• First Submitted That Met QC Criteria: December 18, 2017
• First Posted (ACTUAL): December 20, 2017

Study Record Updates

• Last Update Posted (ACTUAL): December 20, 2017
• Last Update Submitted That Met QC Criteria: December 18, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Rotator Cuff; Human Amniotic Fluid; Amniotic Fluid Allograft; FlōGraft®; Amniotic Fluid Biologic; Fatty Atrophy; Fat Degeneration
• Additional Relevant MeSH Terms: Wounds and Injuries; Rupture; Shoulder Injuries; Tendon Injuries; Pathological Conditions, Anatomical; Rotator Cuff Injuries; Atrophy
• Other Study ID Numbers: TOH169

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No