A Pilot Masked, Randomized Controlled Trial Evaluating Locally-applied Gentamicin versus Saline in Open Tibia Fractures (pGO-Tibia)

一项蒙蔽随机对照试验，评估局部应用庆大霉素与生理盐水治疗开放性胫骨骨折 (pGO-Tibia)

• 批准号: 10392433
• 负责人: David William Shearer
• 金额: $ 16.76万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-15 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10392433
• 关键词: Adult; Advocate; Aminoglycosides; Amputation; Antibiotics; Award; Blood flow; Caring; Chronic; Clinical; Clinical Research; Clinical Trials; Clinical Trials Design; Complication; Cost Effectiveness Analysis; Cost Savings; Data; Data Analyses; Debridement; Disease; Economic Burden; Economics; Effectiveness; Enrollment; Event; Failure; Focal Infection; Fracture; Gentamicins; Genus staphylococcus; Health; Hospital Referrals; Impairment; Infection; Infection prevention; Injections; Injury; Institutes; Intervention Studies; Intravenous; Lead; Leg; Literature; Masks; Measures; Medical Care Costs; Methodology; Modeling; Morbidity - disease rate; North America; Observational Study; Open Fractures; Operative Surgical Procedures; Orthopedics; Osteomyelitis; Outcome; Participant; Patients; Pilot Projects; Placebo Control; Placebos; Population; Powder dose form; Prevention strategy; Principal Investigator; Quality of life; Quality-Adjusted Life Years; Randomized; Randomized Clinical Trials; Randomized Controlled Trials; Repeat Surgery; Research; Research Design; Rod; Saline; Site; Skin; Source; Surgical wound; Survey Methodology; Tanzania; Target Populations; Techniques; Tibial Fractures; Time; Trauma; Vial device; aqueous; bone; bone fracture repair; bone healing; burden of illness; cohort; compare effectiveness; cost; cost effective; cost effectiveness; cost estimate; cost-effectiveness ratio; disability; economic evaluation; economic outcome; experience; fracture risk; healing; health economics; improved outcome; incremental cost-effectiveness; infection risk; innovation; intervention cost; long bone; low income country; markov model; microcosting; multidisciplinary; open wound; pathogen; pilot trial; prevent; primary outcome; prophylactic; prospective; radiological imaging; randomized trial; sample fixation; secondary analysis; secondary outcome; skills; tibia; trauma centers; traumatic wound; treatment group; wound; wound closure

PROJECT SUMMARY/ABSTRACT Tibial shaft fractures are the most common major fracture of the lower leg and are frequently associated with a break in the skin known as an open fracture. Because the bone is exposed by the open wound, open tibial fractures are often complicated by infection and failure of bone healing, which can lead to long-lasting disability and in some cases amputation. Intravenous antibiotics administered early after injury are a well-established measure to prevent fracture-related infection (FRI), but their effectiveness is limited by poor blood flow at the fracture site and inability to achieve high local concentrations with systemic administration. Gentamicin applied locally within the open fracture wound is a promising adjunctive measure to reduce the risk of FRI after these injuries, but there are no high-quality clinical trials evaluating its use. The candidate proposes to gain skills in randomized controlled trials, observational research design, and cost- effectiveness analysis. The primary study is a pilot trial to assess the feasibility of a masked, randomized trial to compare the effectiveness of locally applied gentamicin to saline placebo to prevent FRI after open tibia fractures (aim 1). The study will be conducted at the Muhimbili Orthopaedic Institute, a tertiary referral hospital in Tanzania with a higher rate of open fractures and infection than trauma centers in North America. A secondary analysis of pooled observational data from the pilot trial and prior studies evaluating open tibial fractures will be used to assess the impact of FRI on quality-of-life and fracture healing (aim 2). The cost-effectiveness of local gentamicin will be estimated by gathering cost data alongside the clinical outcomes in the primary study. These data will be projected beyond the trial endpoint using modelling techniques (aim 3). This will be the first randomized trial evaluating locally administered gentamicin to reduce infection in a fracture population. If efficacious, local gentamicin is likely to be a highly cost-effective preventive strategy for FRI and may ultimately be cost saving. Although these findings will originate from a low-income country, results may be generalizable to populations in both high and low-income countries and could therefore significantly reduce the global burden of open fractures. Through the conduct of the proposed studies, the principal investigator will gain skills in clinical trial design, observational data analysis, and economic analysis from a multidisciplinary team of experts in these domains. In addition, the candidate will gain the clinical research experience necessary and generate preliminary data to successfully compete for an R01 award studying interventions that aim to improve outcomes for orthopedic trauma victims.

项目总结/摘要 胫骨干骨折是小腿最常见的主要骨折， 在皮肤上的破裂称为开放性骨折。因为骨头暴露在开放性伤口，胫骨开放性伤口 骨折往往并发感染和骨愈合失败，这可能导致长期残疾 有时甚至截肢创伤后早期静脉注射抗生素是一种公认的 预防尿道相关感染（FRI）的措施，但其有效性受到血流不畅的限制。 骨折部位和全身给药不能达到高局部浓度。应用庆大霉素 在开放性骨折伤口内局部注射是一种很有前途的预防措施，可以降低FRI的风险， 但是没有高质量的临床试验来评估它的使用。 候选人建议获得随机对照试验，观察性研究设计和成本方面的技能。 有效性分析主要研究是一项初步试验，旨在评估一项设盲、随机试验的可行性， 比较局部应用庆大霉素与生理盐水安慰剂预防开放性胫骨骨折后FRI的有效性 (aim 1）。该研究将在坦桑尼亚的三级转诊医院Muhimbili骨科研究所进行 开放性骨折和感染的发生率比北美的创伤中心要高。二次分析 将使用来自初步试验和既往评价开放性胫骨骨折的研究的汇总观察数据， 评估FRI对生活质量和骨折愈合的影响（目的2）。局部应用庆大霉素的成本-效果分析 将通过收集成本数据以及主要研究中的临床结局来估计。这些数据将 使用建模技术预测超出试验终点（目标3）。 这将是第一个评价局部使用庆大霉素减少骨折感染的随机试验 人口如果有效，局部庆大霉素可能是FRI的高成本效益预防策略， 最终可以节省成本。虽然这些研究结果将来自低收入国家，但结果可能会 因此，可大大减少高收入和低收入国家人口的 开放性骨折的全球负担。通过开展拟议的研究，主要研究者将获得 临床试验设计，观察数据分析和经济分析的技能，来自多学科团队， 这些领域的专家。此外，候选人将获得必要的临床研究经验， 生成初步数据，以成功竞争R 01奖，研究旨在改善 骨科创伤受害者的结果。