Design Features and Rationale of the BEAR-MOON (Bridge-Enhanced ACL Restoration Multicenter Orthopaedic Outcomes Network) Randomized Clinical Trial

BEAR-MOON Design Group, Kurt P Spindler, Peter B Imrey, Sercan Yalcin, Gerald J Beck, Gary Calbrese, Charles L Cox, Paul D Fadale, Lutul Farrow, Robert Fitch, David Flanigan, Braden C Fleming, Michael J Hulstyn, Morgan H Jones, Christopher Kaeding, Jeffrey N Katz, Peter Kriz, Robert Magnussen, Ellen McErlean, Carrie Melgaard, Brett D Owens, Paul Saluan, Greg Strnad, Carl S Winalski, Rick Wright, BEAR-MOON Design Group, Kurt P Spindler, Peter B Imrey, Sercan Yalcin, Gerald J Beck, Gary Calbrese, Charles L Cox, Paul D Fadale, Lutul Farrow, Robert Fitch, David Flanigan, Braden C Fleming, Michael J Hulstyn, Morgan H Jones, Christopher Kaeding, Jeffrey N Katz, Peter Kriz, Robert Magnussen, Ellen McErlean, Carrie Melgaard, Brett D Owens, Paul Saluan, Greg Strnad, Carl S Winalski, Rick Wright

Abstract

Background: BEAR (bridge-enhanced anterior cruciate ligament [ACL] restoration), a paradigm-shifting technology to heal midsubstance ACL tears, has been demonstrated to be effective in a single-center 2:1 randomized controlled trial (RCT) versus hamstring ACL reconstruction. Widespread dissemination of BEAR into clinical practice should also be informed by a multicenter RCT to demonstrate exportability and compare efficacy with bone--patellar tendon-bone (BPTB) ACL reconstruction, another clinically standard treatment.

Purpose: To present the design and initial preparation of a multicenter RCT of BEAR versus BPTB ACL reconstruction (the BEAR: Multicenter Orthopaedic Outcomes Network [BEAR-MOON] trial). Design and analytic issues in planning the complex BEAR-MOON trial, involving the US National Institute of Arthritis and Musculoskeletal and Skin Diseases, the US Food and Drug Administration, the BEAR implant manufacturer, a data and safety monitoring board, and institutional review boards, can usefully inform both clinicians on the trial's strengths and limitations and future investigators on planning of complex orthopaedic studies.

Study design: Clinical trial.

Methods: We describe the distinctive clinical, methodological, and operational challenges of comparing the innovative BEAR procedure with the well-established BPTB operation, and we outline the clinical motivation, experimental setting, study design, surgical challenges, rehabilitation, outcome measures, and planned analysis of the BEAR-MOON trial.

Results: BEAR-MOON is a 6-center, 12-surgeon, 200-patient randomized, partially blinded, noninferiority RCT comparing BEAR with BPTB ACL reconstruction for treating first-time midsubstance ACL tears. Noninferiority of BEAR relative to BPTB will be claimed if the total score on the International Knee Documentation Committee (IKDC) subjective knee evaluation form and the knee arthrometer 30-lb (13.61-kg) side-to-side laxity difference are both within respective margins of 16 points for the IKDC and 2.5 mm for knee laxity.

Conclusion: Major issues include patient selection, need for intraoperative randomization and treatment-specific postoperative physical therapy regimens (because of fundamental differences in surgical technique, initial stability construct, and healing), and choice of noninferiority margins for short-term efficacy outcomes of a novel intervention with evident short-term advantages and theoretical, but unverified, long-term benefits on other dimensions.

Keywords: ACL reconstruction; ACL repair; IKDC; RCT; instrumented knee laxity.

Conflict of interest statement

One or more of the authors has declared the following potential conflict of interest or source of funding: see Supplemental Material for details. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

© The Author(s) 2022.

Figures

Figure 1.
Figure 1.
Which is a repairable ACL stump? (A) Repairable; (B) potentially repairable; (C) not repairable. ACL, anterior cruciate ligament.
Figure 2.
Figure 2.
Prospectively-assessed distribution of ages of patients undergoing anterior cruciate ligament (ACL) reconstructions. The dashed lines indicate the boundaries of the age range chosen for eligibility to participate in BEAR-MOON. ACLR, anterior cruciate ligament reconstruction; BEAR-MOON, bridge-enhanced ACL restoration: Multicenter Orthopaedic Outcomes Network.
Figure 3.
Figure 3.
Prospectively-assessed distribution of times from injury to anterior cruciate ligament (ACL) reconstructions. The dashed line indicates the maximal duration from injury to surgery chosen for eligibility to participate in BEAR-MOON. ACLR, anterior cruciate ligament reconstruction; BEAR-MOON, bridge-enhanced ACL restoration: Multicenter Orthopaedic Outcomes Network.
Figure 4.
Figure 4.
Power, depicted over the lower 70% of both noninferiority ranges, for the selected sample size of 200 patients (solid blue curve) under the stated assumptions as well as power curves for recruitment shortfalls or, equivalently, variance increases of 10% and 20% and thus SD increases of 4.8% and 9.5% above the 80th percentiles used for the nominal case (dashed violet curves); or a decrease of 5% or increases of 5% or 10% in the anticipated dropout fraction (dotted orange curves). Plausible increases in the crossover fraction would have substantially smaller effect and are omitted. IKDC, International Knee Documentation Committee; MM, millimeters; NI, noninferiority.

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