The Local Infiltration Therapy (LIT) Trial for Pain Control Following Hip Fracture Fixation

髋部骨折固定后控制疼痛的局部浸润疗法 (LIT) 试验

• 批准号: 10440815
• 负责人: Paul Edward Matuszewski
• 金额: $ 36.99万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-05 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10440815
• 关键词: Address; Agreement; Budgets; Bupivacaine; Certification; Climacteric; Clinical; Clinical Trials; Clinical trial protocol document; Clonidine; Collection; Complication; Consent Forms; Contracts; Data; Data Collection; Databases; Delirium; Double-Blind Method; Drowsiness; Elderly; Enrollment; Ensure; Epinephrine; Evaluation; Exclusion Criteria; Fracture; Fracture Fixation; Goals; Grant; Hip Fractures; Hospitalization; Incentives; Individual; Infiltration; Injection of therapeutic agent; Injections; Institution; Institutional Review Boards; Kentucky; Ketorolac; Liposomes; Literature; Manuals; Methods; Modality; Morbidity - disease rate; Multi-Institutional Clinical Trial; Nausea and Vomiting; Opioid; Orthopedic Procedures; Orthopedics; Outcome; Pain; Pain management; Paper; Patients; Pharmaceutical Preparations; Pharmacy facility; Placebo Effect; Placebos; Population; Postoperative Complications; Postoperative Pain; Preparation; Prevention; Procedures; Process; Protocols documentation; Public Health; Randomized; Replacement Arthroplasty; Reporting; Research; Resources; Retrospective Studies; Risk; Rotator Cuff; Safety; Safety Management; Severities; Site; Spine surgery; Statistical Data Interpretation; Testing; Therapy trial; Training; Trauma; Universities; Urinary Retention; Ventilatory Depression; Visual; Work; age group; analog; base; clinical investigation; clinical research site; cohort; cost; cost effective; data dictionary; data management; data repository; data standards; design; effectiveness evaluation; experience; follow-up; improved; improved outcome; indexing; mortality; novel; older patient; opioid epidemic; opioid use; participant enrollment; payment; placebo controlled trial; prevent; primary endpoint; prospective; randomized placebo controlled trial; recruit; repaired; ropivacaine; screening; secondary endpoint; side effect

Geriatric hip fractures are an increasingly prominent public health problem with more than 300,000 fracture sustained within the U.S. each year and predicted over 1,000,000 by 2050. These fractures are life changing in elderly patients and sustaining a post-operative complication can be severely debilitating. Post-operative pain can be a significant driver of poor outcome via an increased risk of post-operative complications, including delirium which is associated with increased mortality, morbidity and outcome which persists beyond index hospitalization. Pain control is frequently managed with opioids which elderly patients are particularly susceptible to the negative side-effects they entail, which include somnolence, delirium, nausea, vomiting, urinary retention and respiratory depression. Additionally, increased opioid use in the context of the current opioid epidemic is further concerning and elderly patients are just as susceptible as other age groups. Thus, decreasing opioid use in these patients is paramount in decreasing complications and ultimately improving outcome for this deserving group of patients. In a pilot, double-blinded, multi-centered placebo-controlled trial we recently conducted, we reported a decreased use of opioids following hip fracture fixation and decreased pain visual analog scores (VAS) with the usage of liposomal bupivacaine. In a follow-up retrospective study, we demonstrated that the use of an injection cocktail of commonly available medications (Clonidine, Epinephrine, Ropivacaine, Toradol) demonstrated a similar and possibly greater decrease of opioid use and pain VAS when compared to liposomal bupivacaine. The injection cocktail is associated with less cost than the commercial liposomal bupivacaine and may be a more cost-effective alternative to liposomal bupivacaine. Given these findings and large support for both of these modalities in the arthroplasty literature, evaluation of the approach to improve outcomes in the hip fracture population is crucial to helping prevent complications and poor outcomes in these patients. This proposal aims to initiate and complete the planning of a multi-center, double-blind, non-inferiority trial with placebo for effect size determination to test our hypotheses that a pharmacy prepared cocktail is not inferior to a commercially available liposomal bupivacaine, and that local injection therapy can improve pain control following hip fracture fixation. We will utilize existing research relationships between clinical sites to complete the protocol, optimize procedures, prepare a budget, develop protocol forms, optimize recruitment procedures, develop a standard procedures manual, perform regulatory submissions and recruit additional sites as necessary to complete the proposed trial. Given the severity of complications associated with poor pain control, successful planning and completion of this trial can potentially introduce a method of pain control which is opioid free and widely adaptable with minimal resources.

老年髋部骨折是一个日益突出的公共卫生问题， 每年在美国持续，预计到2050年将超过100万。这些骨折改变了我们的生活 在老年患者中，持续的术后并发症可能会使人严重衰弱。术后 疼痛可通过增加术后并发症的风险而成为不良结局的重要驱动因素，包括 谵妄，与死亡率、发病率和结局增加相关，持续超过指数 住院疼痛控制经常使用阿片类药物，老年患者尤其需要 易受其带来的负面副作用的影响，包括嗜睡、谵妄、恶心、呕吐， 尿潴留和呼吸抑制。此外，在目前的背景下， 阿片类药物的流行进一步令人担忧，老年患者与其他年龄组一样易受影响。因此，在本发明中， 在这些患者中减少阿片类药物的使用对于减少并发症和最终改善 为这群有价值的患者提供了一个好的结果。在一项初步、双盲、多中心安慰剂对照试验中 我们最近进行了研究，我们报告了髋部骨折固定后阿片类药物的使用减少， 使用脂质体布比卡因的疼痛视觉模拟评分（VAS）。在一项后续的回顾性研究中， 我们证明了使用常用药物（可乐定， 肾上腺素、罗哌卡因、托拉多）表现出类似的，可能更大的阿片类药物使用减少， 与布比卡因脂质体相比的疼痛VAS。注射混合物与比注射混合物更低的成本相关。 商品化的脂质体布比卡因，并且可能是脂质体布比卡因的更具成本效益的替代物。 鉴于这些发现和关节置换术文献中对这两种方式的大量支持， 改善髋部骨折人群结局的方法对于帮助预防并发症至关重要， 这些患者的预后不佳。本提案旨在启动并完成多中心规划， 一项双盲、非劣效性试验，用安慰剂确定效应量，以检验我们的假设， 药学上制备的鸡尾酒不劣于市售的脂质体布比卡因，并且局部 注射疗法可以改善髋部骨折固定后的疼痛控制。我们将利用现有的研究 临床研究中心之间的关系，以完成方案，优化程序，编制预算， 方案表格，优化招募程序，制定标准程序手册，执行监管 必要时提交并招募额外的研究中心以完成拟定试验。考虑到 与疼痛控制不良相关的并发症，成功的计划和完成本试验可能 介绍一种不含阿片类药物并可广泛适用于最少资源的疼痛控制方法。