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 关节内的组织，包括前交叉韧带、肩袖肌腱、半月板和 唇在受伤后不能自发愈合，且具有高手术修复失败率。ACL表示 研究关节内愈合问题的良好模型，因为有经过验证的临床前模型， 临床结局指标，使其有可能批判性地评估策略的成功或失败， 促进组织愈合。目前ACL损伤的护理标准是ACL重建， 但是需要损害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，尽管有ACL，但早期创伤后OA并未减轻 重建关于ACL修复的临床前研究称为BEAR（桥接增强ACL修复） 证明了预防创伤后OA并实现了膝关节稳定性。积极的临床前发现， 与ACL重建相比，BEAR为两项FDA批准的初步临床研究奠定了基础。 试验：1）首次人体队列研究（“BEAR I”），和2）小型单中心随机对照试验 （“熊II”）。我们的试点数据的统计分析显示，需要200名患者的试验来证明 与ACL重建相比，BEAR（一种新型范式改变技术）的非劣效性 （当前的金标准），用于前后（AP）膝关节松弛的关键结局和经验证的患者 报告了膝关节手术的结局。因此，我们提出了BEAR-MOON（桥接增强ACL修复） 共同主要结局AP（前后）膝关节松弛的多中心随机非劣效性临床试验 和国际膝关节文献委员会（IKDC）确认的患者报告结局指标。的 受试者年龄在18 - 40岁之间，ACL完全撕裂，随机分配至1）ACL 自体髌腱移植物（ACLR）重建或2）桥接增强ACL修复（BEAR）。我们将 术后6个月、1年和2年随访受试者。虽然实现这些目标有可能 改变ACL手术的临床实践，影响可能会更大，因为FDA- 可用于向关节内的组织递送复杂生物疗法的经批准的载体可以使 在再生医学的多个领域进行的临床前研究的临床翻译， 为这些治疗提供递送载体。