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

项目总结 每年有40多万名患者受到前交叉韧带损伤的影响。我们目前最好的治疗方法是前交叉韧带 重建，撕裂的前交叉韧带被移除，取而代之的是收获的肌腱移植 从膝盖的另一部分。前交叉韧带重建在以下方面具有很高的成功率 使患者恢复运动和日常生活活动。然而，患者不仅要等待 在移植物愈合之前，他们还必须愈合移植物收获的区域。连 通过高强度的物理治疗，患者的腿筋通常仍有高达30%的缺陷。 肌腱移植后6个月的肌力。此外，早产的高比率 骨关节炎-损伤后14年内高达76%，在前交叉韧带重建后出现，如 青少年的失败率也很高。因此，治疗前交叉韧带损伤的新方法 都是有意义的。其中一种方法是“桥接增强前交叉韧带修复术(Bear)”，其中缝线 前交叉韧带的修复辅以生物活性支架。在临床前试验中，这项技术 在关节的机械稳定性方面显示出与前交叉韧带重建相同的结果 接受桥式修复的患者膝关节骨关节炎明显较少。 前交叉韧带重建术。 凭借这些有希望的临床前结果，我们已经获得了FDA的批准，目前正在 进行了一项20名患者的首例人类熊技术研究。以令人振奋的结果 在这项研究中，我们现在建议进行一项有100名患者参加的多中心随机对照试验 Bear技术与前交叉韧带重建术的比较。在这项U34临床试验中提出的工作 试验计划拨款申请将使我们能够选择适当数量的地点，以确保 及时报名，完成所有方案和规范材料，竞争自我报告 评估工具，优化数据管理计划，增强提供商在以下方面的平衡 对所有地点的外科医生进行登记和干预、交付和完成外科培训。 最初参与试验的地点包括波士顿儿童医院、俄亥俄州立大学、 华盛顿大学圣路易斯分校和克利夫兰诊所。波士顿儿童医院是 桥式增强前交叉韧带修复技术已经开发出来，这是人类第一个 审判正在进行中。俄亥俄州立大学、华盛顿大学和克利夫兰诊所 是否所有网站都有招募患者进行前交叉韧带研究的良好记录，包括多中心 矫形外科结果网络(MON)研究。通过这些人的共同努力 站点，我们将能够为成功的多站点试验设计和准备文档 一种有前景的桥式增强前交叉韧带修复的新疗法 治疗，前交叉韧带重建。

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.