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.

项目概要 关节内的组织，包括前十字韧带、肩袖肌腱、半月板和 盂唇损伤后不能自然愈合，手术修复失败率较高。 ACL 代表 一个很好的模型来研究关节内愈合问题，因为有经过验证的临床前模型和 临床结果测量，使批判性评估策略的成功或失败成为可能 增强组织愈合。目前 ACL 损伤的护理标准是 ACL 重建，其擅长 稳定膝盖，但需要损害膝盖周围其他未受伤的结构以获得移植物 随后用于替换 ACL。此外，尽管存在 ACL，但早期创伤后 OA 并未得到缓解 重建。 ACL 修复的临床前研究称为 BEAR（桥增强型 ACL 修复） 证明可以预防创伤后 OA 并实现膝关节稳定性。积极的临床前发现 BEAR 与 ACL 重建的比较为 FDA 批准的两项初步临床提供了基础 试验：1) 首次人体队列研究（“BEAR I”），2) 一项小型单中心随机对照试验 （“熊二”）。我们的试点数据统计分析显示，需要 200 名患者进行试验才能证明 与 ACL 重建相比，BEAR（一种新颖的范式改变技术）具有非劣性 （当前黄金标准）前后（AP）膝关节松弛的关键结果和经过验证的患者 报告膝关节手术的结果。因此我们提出BEAR-MOON（桥增强型ACL修复） 共同主要结果 AP（前后）膝关节松弛的多中心随机非劣效性临床试验 国际膝关节文献委员会 (IKDC) 验证了患者报告的结果测量。这 受试者年龄在 18 至 40 岁之间，患有 ACL 完全撕裂，并随机分配至 1) ACL 使用髌腱自体移植物 (ACLR) 进行重建或 2) 桥增强型 ACL 修复术 (BEAR)。我们将 在手术后 6 个月、1 和 2 年对受试者进行随访。实现这些目标的同时有可能 改变 ACL 手术的临床实践，影响可能会更大，因为 FDA 的可用性 经批准的载体可用于向关节内的组织提供复杂的生物疗法，可以使 再生医学多个领域进行的临床前研究的临床转化 为这些疗法提供载体。