A Masked, Randomized Controlled Trial Evaluating Locally-applied Gentamicin Versus Saline in Open Tibia Fractures
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 890
- 试验地点
- 1
- 主要终点
- Occurrence of fracture-related infection (FRI)
研究概览
简要总结
Local application of antibiotics directly to the traumatic wound is a promising treatment for the prevention of infection after open tibia fractures, which are a significant source of disease burden globally, particularly in low-income countries. This study aims to measure the effect of locally applied gentamicin on risk of infection for open tibial fractures in Tanzania. If proven effective, local gentamicin would be a highly cost-effective strategy to reduce complications and disability from open tibial fractures that could impact care in both high- and low-income countries.
详细描述
Tibial shaft (shinbone) 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.
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Data collectors (research coordinators) and data analysts will also be masked
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age>18 years old
- •Open tibial shaft fracture meeting the following criteria:
- •Orthopaed Trauma Association (OTA) Type 42
- •Primarily closable wound
- •Gustilo-Anderson (GA) Type I, II, or IIIA
排除标准
- •Time from injury to presentation > 48 hours
- •Time from injury to surgery > 7 days
- •Aminoglycoside allergy
- •GA IIIB or IIIC open fractures
- •Bilateral open tibial fractures
- •Severe brain (GCS<12) or spinal cord injury
- •Severe vascular injury
- •Severe burns (>10% Total Body Surface Area (TBSA) or >5% TBSA with full thickness or circumferential injury)
- •Pathologic fracture
- •History of active limb infection, ipsilaterally
- •Unlikely to complete follow-up
研究组 & 干预措施
Gentamicin
The intervention consists of 80mg of liquid gentamicin diluted in 5 mL normal saline (16mg/mL). The solution is injected by inserting a 22-gauge needle down to bone through an anteromedial approach at the level of the fracture site such that the injected solution fills the wound cavity. A total of 5mL of study solution will be administered.
干预措施: Gentamicin (Drug)
Saline
The control consists of 5 mL normal saline injected immediately after wound closure at the open fracture site. The solution is injected by inserting a 22-gauge needle down to bone through an anteromedial approach at the level of the fracture site such that the injected solution fills the wound cavity. A total of 5mL of study solution will be administered.
干预措施: normal Saline (Drug)
结局指标
主要结局
Occurrence of fracture-related infection (FRI)
时间窗: 12 months
Fracture-related infection is a consensus definition of infection after fracture treatment. It is diagnosed by an orthopaedic surgeon based on any of the following four diagnostic criteria: (1) fistula, sinus or wound breakdown; (2) purulent drainage from the wound or presence of pus during surgery; (3) phenotypically indistinguishable pathogens identified by culture from at least two separate deep tissue/implant specimens; or (4) presence of microorganisms in deep tissue taken during an operative intervention, as seen on histopathological examination. FRI diagnosis is likely to peak between 6 weeks and 6 months after surgery and has a non-normal time-to-event distribution, with incident cases rarely presenting later than 12 months after surgery. All events will be confirmed by an independent adjudication committee comprised of three masked, non-treating orthopaedic trauma surgeons.
次要结局
- Occurrence of unplanned fracture-related reoperation(12 months)
- Health-related quality-of-life (HRQOL) as measured by EQ-5D-3L (Swahili version)(12 months)
- Fracture healing by modified Radiographic Union Scale for Tibial fractures (mRUST score)(12 months)
- Clinical fracture healing by Function IndeX for Trauma (FIX-IT)(12 months)
- Occurrence of nonunion(12 months)
- Occurence of FRI Suggestive Criteria(12 months)