BEAR-MOON: A Two Arm Noninferiority Blinded Randomized Clinical Trial Comparing ACL Repair with BEAR Device vs. Standard of Care Autograft Patellar Tendon ACL Reconstruction

BEAR-MOON：一项两臂非劣效性盲法随机临床试验，比较使用 BEAR 装置进行 ACL 修复与自体移植髌腱 ACL 重建的护理标准

• 批准号: 9751779
• 负责人: Kurt Paul Spindler
• 金额: $ 121.72万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9751779
• 关键词: Affect; Age-Years; Animal Model; Anterior; Anterior Cruciate Ligament; Area; Autologous; Autologous Transplantation; Biological; Biological Response Modifier Therapy; Blinded; Blood; Clinical; Clinical Trials; Cohort Studies; Complex; Data; Degenerative polyarthritis; Devices; Documentation; Enrollment; Environment; FDA approved; Failure; Foundations; Funding; Gold; Harvest; Human; Inferior; Injury; International; Joints; Knee; Knee Osteoarthritis; Lead; Ligaments; Measures; Meniscus structure of joint; Meteor; Modeling; Operative Surgical Procedures; Orthopedics; Outcome; Outcome Measure; Pathology; Patient Outcomes Assessments; Patients; Physical Examination; Pre-Clinical Model; Preclinical Testing; Prevention; Procedures; Protocols documentation; Randomized; Randomized Clinical Trials; Randomized Controlled Clinical Trials; Regenerative Medicine; Research Personnel; Rotator Cuff; Running; Safety; Scaffolding Protein; Site; Statistical Data Interpretation; Structure; Synovial Fluid; Techniques; Technology; Tendon structure; Testing; Time; Tissue Engineering; Tissue Harvesting; Tissues; United States National Institutes of Health; Work; Wound Healing; anterior cruciate ligament healing; anterior cruciate ligament reconstruction; anterior cruciate ligament rupture; arm; clinical practice; clinical translation; cohort; control trial; effusion; experience; first-in-human; healing; health related quality of life; injured; mechanical properties; novel; patellar tendon; pre-clinical; preclinical study; premature; primary endpoint; primary outcome; repaired; scaffold; standard of care; success; trial comparing

PROJECT SUMMARY Tissues which live within joints, including the anterior cruciate ligament, rotator cuff tendon, meniscus and labrum fail to heal spontaneously after injury and have high failure rates of surgical repair. The ACL represents a good model to study the problem of intra-articular healing as there are validated preclinical models and clinical outcome measures that make it possible to critically evaluate the success or failure of strategies to enhance tissue healing. The current standard of care for ACL injuries is ACL reconstruction, which is good at stabilizing the knee but requires compromising other uninjured structures around the knee to obtain a graft that is subsequently used to replace the ACL. Further the early posttraumatic OA is not mitigated despite ACL reconstruction. The preclinical studies on ACL repair called BEAR (Bridge-Enhanced ACL Repair) demonstrated a prevention of posttraumatic OA and achieved knee stability. The positive preclinical findings of BEAR compared to ACL reconstruction provided the foundation for two FDA approved preliminary clinical trials: 1) the first-in-human cohort study (“BEAR I”), and 2) a small, single-center randomized control trial (“BEAR II”). The statistical analysis of our pilot data shows a 200 patient trial will be required to demonstrate non-inferiority of BEAR (a novel paradigm changing technology) when compared to ACL reconstruction (current gold standard) for the key outcomes of anterior-posterior (AP) knee laxity and a validated patient reported outcome for knee surgery. Therefore we propose the BEAR-MOON (Bridge-Enhanced ACL Repair) multi-center randomized non-inferiority clinical trial for co-primary outcomes AP (anterior-posterior) knee laxity and International Knee Documentation Committee (IKDC) validated patient reported outcome measure. The subjects will be between 18 and 40 years of age with a complete ACL tear and randomized to either 1) ACL Reconstruction with patellar tendon autograft (ACLR) or 2) Bridge-Enhanced ACL Repair (BEAR). We will follow subjects at 6 months, 1 and 2 years after surgery. While achieving these aims has the potential to change the clinical practice of ACL surgery, the impact is potentially far greater, as the availability of an FDA- approved carrier that can be used to deliver complex biologic therapies to tissues within joints could enable the clinical translation of the preclinical studies being conducted in multiple areas of regenerative medicine by providing a delivery vehicle for these therapies.

项目总结 关节内的组织，包括前交叉韧带、肩袖肌腱、半月板和 唇部损伤后不能自行愈合，手术修复失败率高。该ACL代表 研究关节内愈合问题的一个很好的模型，因为有经过验证的临床前模型和 临床结果测量，使其能够批判性地评估治疗策略的成败 促进组织愈合。目前对前交叉韧带损伤的护理标准是前交叉韧带重建，这是擅长的 稳定膝关节，但需要损害膝盖周围其他未受伤的结构，以获得 随后被用来替换该ACL。此外，尽管有前交叉韧带，早期创伤后骨性关节炎仍未得到缓解 重建。前交叉韧带修复(BEAR)的临床前研究 展示了一种预防创伤后骨关节炎的方法，并实现了膝关节的稳定。阳性的临床前发现 熊掌前交叉韧带重建为FDA批准的两项初步临床提供了基础 试验：1)首例人类队列研究(“Bear I”)；2)一项小型、单中心随机对照试验 (“熊II”)。我们对试点数据的统计分析表明，需要200名患者进行试验才能证明 与前交叉韧带重建相比，Bear的非劣性(一种新的范式改变技术) (目前的黄金标准)膝关节前-后(AP)松弛的关键结果和一名经过验证的患者 报告了膝关节手术的结果。因此，我们提出了Bear-Moon(桥接增强型前交叉韧带修复) 膝关节前后部松弛共同预后的多中心随机非劣势临床试验 和国际膝关节文件委员会(IKDC)确认患者报告的结果。这个 受试者年龄在18岁至40岁之间，前交叉韧带完全撕裂，随机分为两组 2)桥接增强前交叉韧带修复术(BEST)。我们会 分别于术后6个月、1年和2年对受试者进行随访。虽然实现这些目标有可能 改变前交叉韧带手术的临床实践，其影响可能要大得多，因为FDA的可用性- 经批准的载体可用于向关节内的组织输送复杂的生物疗法，可以使 在再生医学的多个领域进行的临床前研究的临床翻译 为这些疗法提供了一种运送工具。