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: 10604256
• 负责人: David William Shearer
• 金额: $ 16.7万
• 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/10604256
• 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; Intervention Studies; Intravenous; 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; Placebos; Population; Powder dose form; Prevention strategy; Principal Investigator; Quality of life; Quality-Adjusted Life Years; Randomized; Randomized, Controlled Trials; Repeat Surgery; Research; Research Design; Risk Reduction; 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; clinical trial enrollment; cohort; compare effectiveness; cost; cost effective; cost effectiveness; cost estimate; cost-effectiveness ratio; disability; economic evaluation; economic outcome; experience; fracture risk; healing; 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 placebo-controlled clinical trial; randomized trial; randomized, clinical trials; 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.

项目摘要/摘要 胫骨骨折是下腿最常见的主要裂缝，经常与 在皮肤中折断被称为开放裂缝。因为骨头被敞开的伤口暴露，所以开放的胫骨 骨折通常因感染和骨骼愈合的失败而变得复杂，这可能导致持久的残疾 在某些情况下截肢。受伤后提早服用的静脉注射抗生素是一个完善的 预防骨折相关感染（FRI）的措施，但其有效性受到血液流量不佳的限制 断裂部位，无法通过全身给药实现高局部浓度。庆大霉素应用 在开放骨折伤口内本地是一种有前途的辅助措施，可降低周五之后的风险 受伤，但没有评估其使用的高质量临床试验。 候选人提议在随机对照试验，观察性研究设计和成本 - 有效分析。主要研究是一项试验试验，以评估掩盖，随机试验的可行性 比较局部施用庆大霉素对盐碱安慰剂的有效性，以防止胫骨骨折后周五 （目标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 与北美的创伤中心相比，开放裂缝和感染的率更高。二次分析 试验试验的合并观察数据和评估开放性胫骨骨折的先前研究将用于 评估周五对生活质量和骨折愈合的影响（AIM 2）。当地庆大霉素的成本效益 将通过收集成本数据以及主要研究中的临床结果来估算。这些数据将是 使用建模技术（AIM 3）超越试验端点。 这将是评估本地施用庆大霉素以减少骨折中感染的第一个随机试验 人口。如果有效的话，当地庆大霉素可能是周五和 最终可能会节省成本。尽管这些发现将来自一个低收入国家，但结果可能是 在高收入国家和低收入国家的人口中都可以大大减少 全球开放裂缝负担。通过拟议的研究的进行，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R01奖励研究旨在改善的干预措施 骨科创伤受害者的结果。