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

项目摘要/摘要 胫骨骨干骨折是小腿最常见的主要骨折，常与 皮肤破裂，称为开放性骨折。因为骨头被开放的伤口暴露，开放的胫骨 骨折经常合并感染和骨愈合失败，这可能导致长期的残疾。 在某些情况下还会截肢。伤后早期静脉注射抗生素是一种行之有效的方法。 预防骨折相关感染(FRI)的措施，但其有效性因骨折部位血流不畅而受到限制 骨折部位，全身给药无法达到较高的局部浓度。应用庆大霉素 在开放性骨折伤口内局部是一种有希望的辅助措施，可以降低术后再发骨折的风险。 但目前还没有高质量的临床试验来评估它的使用。 候选人建议在随机对照试验、观察性研究设计和成本方面获得技能- 有效性分析。主要研究是一项试点试验，以评估掩蔽随机试验的可行性 庆大霉素局部应用与生理盐水安慰剂预防开放性胫骨骨折后并发骨折的疗效比较 (目标1)。这项研究将在坦桑尼亚的三级转诊医院穆亨比利整形外科研究所进行 与北美的创伤中心相比，开放性骨折和感染率更高。二次分析 来自试点试验和先前评估开放性胫骨骨折的研究的汇集观察数据将被用于 评估放射治疗对生活质量和骨折愈合的影响(目标2)。国产庆大霉素的成本-效果分析 将通过收集成本数据以及初步研究中的临床结果来估计。这些数据将是 使用建模技术在试验终点之外进行预测(目标3)。 这将是第一个评估局部应用庆大霉素以减少骨折感染的随机试验。 人口。如果有效，当地的庆大霉素很可能是一种成本效益很高的周五和 最终可能是节省成本。尽管这些发现将来自一个低收入国家，但结果可能是 可推广到高收入和低收入国家的人口，因此可以显著减少 开放性骨折的全球负担。通过进行拟议的研究，首席调查员将获得 来自多学科团队的临床试验设计、观察数据分析和经济分析技能 这些领域的专家。此外，应聘者将获得必要的临床研究经验和 生成初步数据以成功竞争R01奖，研究旨在改进的干预措施 骨科创伤受害者的结局。

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.