Clinical trial NCT03776162: A Comparison of ACL Repair With BEAR Device vs. Autograft Patellar Tendon ACL Reconstruction
Official title: BEAR - MOON: A Two Arm Non-Inferiority Randomized Clinical Trial Comparing ACL Repair With BEAR Device vs. Autograft Patellar Tendon ACL Reconstruction
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Anterior Cruciate Ligament Tear
Keywords: Anterior Cruciate Ligament Tear
Anterior Cruciate Ligament Reconstruction
Anterior Cruciate Ligament Repair
Knee Surgery
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
Collaborators: name: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
name: Miach Orthopaedics
First posted: 2018-12-14
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multi-center, 2-arm, 1:1 permuted block randomized controlled clinical trial, with a blinded patient and outcome assessor.
Primary purpose: TREATMENT

Brief summary: This study is designed to evaluate bridge-enhanced ACL restoration (BEAR), a new surgical technique for repairing knees injured by a tear of the anterior cruciate ligament (ACL) that promotes reattachment and healing of the ACL using a blood-enriched implant. BEAR will be compared to bone to patellar tendon to bone autograft (BPTB) reconstruction, a standard ACL surgical reconstruction technique that replaces a torn portion of the ACL with transplanted patellar tendon tissue, and thus requires additional invasive patellar tendon removal and reuse as a portion of the ACL surgery, in a two group randomized clinical trial (RCT) in which participants will have equal chance of receiving BEAR or BPTB reconstruction. The BEAR technique is FDA approved and involves surgically placing a sponge (the BEAR implant) between the torn ends of the ACL, providing an absorbable implant for the ligament ends to grow into. The investigators hypothesize that the ACL repair with BEAR technology will achieve results not appreciably worse than BPTB reconstruction, with a reduced burden of invasive surgery, when assessed over the first two post-operative years. Animal studies suggest BEAR may also ameliorate longer-term premature osteoarthritis of the knee, a common consequence of ACL reconstruction surgery. However, no human data yet support that, and this trial will conclude before such a benefit can be observed. All patients 18-55 years of age who are candidates for ACL surgery within 50 days of the ACL injury and who present to surgeons participating in the study will be offered participation in the trial. Patients will be randomized and will undergo specified rehabilitation protocols post-operatively with primary assessments of knee laxity and patient reported measures at 6 months, 1 year, and 2 years.

Detailed description: The study population will include active and otherwise healthy patients of both genders, all races, and between 18-55 years old at any of six locations, who elect to undergo primary surgery for a torn ACL within 50 days of injury. Approximately 100 patients will receive each of the experimental BEAR surgery and the comparative control BPTB reconstruction surgery, with each group distributed similarly across the six medical centers where the trial is being conducted: Cleveland Clinic, Vanderbilt University, Ohio State University, Rhode Island Hospital/University Orthopedics, and University of Colorado . The study intervention uses a BEAR implant, which is placed between the torn ends of the ruptured ACL. The BEAR implant is resorbed over 4 to 8 weeks, during which period it promotes repair of the ACL tissue in the gap between the torn ends. The device provides a stable provisional sponge to facilitate intra-articular repair of the torn ACL ligament, where without the implant device, healing does not occur. The results of this BEAR procedure will be compared against ACL reconstruction using a BPTB autograft. This technique consists of removing the torn ACL tissue, harvesting patellar tendon, and grafting that tendon within tunnels in the bone to reconstruct or replace the torn ACL. The study duration is five years. Surgery will occur at most 50 days after the patient's ACL is torn, with two year follow-up and a three month window for the final follow-up examination, for a maximum enrollment period for each patient of approximately 2 years and five months (29 months). Randomization will occur during the surgery, and patients will be informed of their treatments at conclusion of their participation. The two research time points are 1 and 2 years, when assessments will be conducted by an independent examiner masked to the type of surgery the patient received. With the exception of the RCT consenting process, use of the BEAR implant, and the blinded assessment process, clinical care will be standard practice following surgical treatment for a torn ACL.

Eligibility criteria: INCLUSION CRITERIA

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. 18-55 years of age
2. Complete ACL tear as confirmed by MRI
3. Selected surgical treatment of ACL injury
4. Believed to be a surgical candidate for ACL reconstruction by treating physician
5. Time from injury to surgery is ≤50 days
6. Stated willingness to comply with all study procedures for the duration of the study, including lifestyle, activity, and sports restrictions
7. Provision of signed and dated informed consent form

EXCLUSION CRITERIA AT PRE-OPERATIVE EXAM

An individual who meets any of the following criteria, either during a pre-operative exam or during intraoperative arthroscopic evaluation, will be excluded from participation in this study:

1. Any prior ACL surgery on affected knee (except simple arthroscopy for plica, debris removal, or diagnosis)
2. Any prior ACL surgery on unaffected knee (except simple arthroscopy for plica, debris removal, diagnosis or partial meniscectomy)
3. Confirmed or suspected contralateral ACL tear
4. ACL tear found to be only partial and the treating physician feels it does not require surgery because it is "stable"
5. Diagnosis of posterolateral corner injury (complete lateral collateral ligament tear, biceps femoris tendon avulsion, arcuate ligament tear, popliteus ligament tear) that requires concurrent or staged surgical treatment
6. Diagnosis of Grade III medial collateral injury that requires concurrent or staged surgery
7. Insufficient ACL tissue on MRI
8. Diagnosis of complete patellar dislocation
9. Diagnosis of complete patellar tendon or quadriceps tear
10. Obesity with a BMI ≥45
11. Does not speak or understand English
12. Daily smoking (occasional or social use is accepted if smoking ≤ 3 days/ week and ≤ 5 cigarettes/day)
13. Documented history of illicit drug or alcohol abuse (except for recreational use of marijuana)
14. Inability to take oral medications
15. Use of intra-articular corticosteroids in the affected knee within last 6 months
16. Chronic use of corticosteroids for treatment of an autoimmune disorder such as lupus, rheumatoid arthritis, etc. (maintenance or rescue inhaler for asthma is allowed)
17. History of prior infection in knee
18. History of chemotherapy treatment
19. History of sickle cell disease
20. History of anaphylaxis, requiring a documented medical intervention
21. Any condition that, in the opinion of the investigator, could affect healing (e.g., diabetes, inflammatory arthritis, etc.)
22. Pregnancy or lactation
23. Known allergic reactions to meat products or collagen
24. Known allergy to bovine collagen, bovine gelatin, or other bovine products
25. Known adverse reaction to any bovine product
26. Febrile illness within 7 days
27. Treatment with another investigational drug or other intervention, either concurrently or previously, that would interfere with surgical healing
28. Not considered by treating physician to be a good research candidate

EXCLUSION CRITERIA AT INTRAOPERATIVE ARTHROSCOPIC EVALUATION

1. Time from injury to surgery has exceeded 50 days
2. No ACL tear found upon arthroscopic inspection
3. ACL tear found to be only partial, with normal pivot shift and endpoint, and does not require surgery
4. Displaced bucket handle meniscal injury requiring repair
5. Diagnosis of full-thickness chondral injury of Grade 3 or 4, or that requires more than microfracture (i.e., osteochondral autograft transplant), on either condyle
6. Unrecognized lateral or medial sided Grade 3 ligamentous injury that requires concurrent or staged surgery
7. Tibial stump length is \< 1cm
8. Tibial footprint attachment is \< 50% intact
9. Any other reason the ACL stump should be deemed irreparable (e.g., tissue quality too poor to hold suture)

Primary outcomes:
measure: KT-1000
timeFrame: KT-1000 instrumented knee laxity measure 2 years after surgery (difference from contralateral knee)
measure: IKDC (International Knee Documentation Committee) Score
timeFrame: Validated Patient Reported IKDC Subjective Score Instrument 2 years after surgery (change from baseline)
Secondary outcomes:
measure: The Knee Injury and Osteoarthritis Outcome Score (KOOS)
timeFrame: Validated Patient Reported KOOS Subjective Score Instrument 2 years after surgery
measure: MARX Activity (Marx Activity Rating Scale)
timeFrame: MARX Activity 2 years after surgery
measure: Anterior Knee Pain Scale (AKPS)
timeFrame: AKPS 2 years after surgery
measure: Quadriceps Strength Testing
timeFrame: Quadriceps Strength 2 years after surgery
measure: Hop Test Limb Difference
timeFrame: Hop Test Limb Difference 2 years after surgery
measure: Active Knee Range of Motion
timeFrame: Active Knee Range of Motion 2 years after surgery
measure: Lachman Testing
timeFrame: Lachman Testing 2 years after surgery
measure: Number of Participants with Knee Infection
timeFrame: Knee Infection 2 years after surgery
measure: Number of Participants with Treatment Failure
timeFrame: Treatment Failure 2 years after surgery
Other outcomes:
Locations:
city: Boulder
country: United States
facility: University of Colorado
state: Colorado
city: Bloomington
country: United States
facility: TRIA Orthopaedics Center/ University of Minnesota
state: Minnesota
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Providence
country: United States
facility: University Orthopedics Institute/ Rhode Island Hospital
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
Study officials:
affiliation: The Cleveland Clinic
name: Kurt P Spindler, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: BEAR-MOON; Vega JF, Strnad GJ, Briskin I, Cox CL, Farrow LD, Fadale P, Flanigan D, Hulstyn M, Imrey PB, Kaeding CC, Owens BD, Saluan P, Wright R, Yen YM, Spindler KP. Interrater Agreement of an Arthroscopic Anterior Cruciate Ligament Tear Classification System. Orthop J Sports Med. 2020 Dec 3;8(12):2325967120966323. doi: 10.1177/2325967120966323. eCollection 2020 Dec.
citation: BEAR-MOON Design Group; Spindler KP, Imrey PB, Yalcin S, Beck GJ, Calbrese G, Cox CL, Fadale PD, Farrow L, Fitch R, Flanigan D, Fleming BC, Hulstyn MJ, Jones MH, Kaeding C, Katz JN, Kriz P, Magnussen R, McErlean E, Melgaard C, Owens BD, Saluan P, Strnad G, Winalski CS, Wright R. Design Features and Rationale of the BEAR-MOON (Bridge-Enhanced ACL Restoration Multicenter Orthopaedic Outcomes Network) Randomized Clinical Trial. Orthop J Sports Med. 2022 Jan 25;10(1):23259671211065447. doi: 10.1177/23259671211065447. eCollection 2022 Jan.