Planning A Clinical Trial of Bio-enhanced ACL Repair versus ACL Reconstruction

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PROJECT SUMMARY ACL injuries affect over 400,000 patients each year. Our current best treatment is ACL reconstruction, where the torn ACL is removed and replaced with a graft of tendon harvested from another part of the knee. ACL reconstruction has a high rate of success in terms of returning patients to sport and activities of daily living. However, patients not only have to wait until the graft heals in, they also have to heal the area where the graft was harvested. Even with intense physical therapy, patients often still have as high as a 30% deficit in hamstring strength 6 months after a hamstring tendon graft is used. In addition, high rates of premature osteoarthritis - as high as 76% within 14 years of injury, are seen after ACL reconstruction, as well as high failure rates in adolescents. For this reason, new methods of treating ACL injuries are of interest. One such method is "Bridge-Enhanced ACL Repair (BEAR)", where a suture repair of the ACL is supplemented with a bioactive scaffold. In preclinical trials, this technique has shown equivalent results to ACL reconstruction in terms of mechanical stability of the joint and knees treated with bridge-enhanced repair had significantly less osteoarthritis than those treated with ACL reconstruction. With these promising preclinical results, we have obtained FDA approval and are currently conducting a 20-patient first-in-human study of the BEAR technique. With the promising results of that study, we now propose to conduct a 100-patient multicenter randomized controlled trial comparing the BEAR technique with ACL reconstruction. The work proposed in this U34 clinical trial planning grant application will allow us to select the appropriate number of sites to ensure timely enrollment, complete all protocols and regulatory materials, compete the self-report assessment tools, optimize the data management plan, enhance provider equipoise regarding enrollment and intervention delivery and complete surgical training for surgeons at all sites. The initial sites to be in the trial include Boston Children's Hospital, Ohio State University, Washington University St Louis and the Cleveland Clinic. Boston Children's Hospital is where the bridge-enhanced ACL repair technique has been developed and where the first-in-human trial is being conducted. Ohio State University, Washington University, and the Cleveland Clinic are all sites with a strong record of recruiting patients for ACL studies, including the Multicenter Orthopaedic Outcomes Network (MOON) studies. Through the collaborative effort of these sites, we will be able to design and prepare the documentation for a successful multi-site trial of a promising new treatment of bridge-enhanced ACL repair with our current gold standard of treatment, ACL reconstruction.