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.

项目摘要 生活在关节内的组织，包括前交叉韧带，肩袖肌腱，弯月面和 唇部受伤后，唇部无法愈合，并且手术修复的失败率很高。 ACL代表 一个很好的模型，用于研究关节内愈合问题，因为有经过验证的临床前模型和 临床结果指标使得有可能评估策略的成功或失败 增强组织愈合。 ACL损伤的当前护理标准是ACL重建，这擅长于 稳定膝盖，但需要妥协膝盖周围的其他未受伤的结构，以获得移植物 随后用于替换ACL。此外，创伤后的OA没有缓解目的地ACL 重建。 ACL修复的临床前研究称为熊（桥梁增强的ACL修复） 表现出预防创伤后的OA并达到膝盖稳定性。积极的临床前发现 与ACL重建相比，熊为两个FDA批准的初步临床提供了基础 试验：1）第一个人类队列研究（“熊I”）和2）一项小的单中心随机对照试验 （“熊II”）。我们的试点数据的统计分析表明，将需要200例患者试验以证明 与ACL重建相比 （当前的金标准）前后后验（AP）膝盖和经过验证的患者的关键结果 报告的膝盖手术结果。因此，我们提出了熊月（桥梁增强的ACL修复） 多中心的随机非效率临床试验，用于共同结果AP（前后）膝关节激光器 国际膝盖文件委员会（IKDC）验证了患者报告的结果指标。这 受试者的年龄在18至40岁之间，完整的ACL撕裂，然后随机分配到1）ACL 用pat肌肌腱自体移植（ACLR）或2）桥梁增强的ACL修复（BEAR）重建。我们将 在手术后6个月，1和2年的时间跟随受试者。实现这些目标有可能 改变ACL手术的临床实践，影响可能更大，因为FDA-的可用性 可用于将复杂生物疗法传递到关节内组织的批准载体可以使 通过在再生医学多个领域进行的临床前研究的临床翻译 为这些疗法提供送货工具。