Routine vs. Clinically-Directed Antibiotic Treatment in Snake Bite With Local Envenomation: a Randomised Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Clinical failure
研究概览
简要总结
Clinicians tend to overuse antibiotics in snake bite despite evidence from three previous clinical trials that failed to show a benefit. But, none of these trials was done in India. Further, the species of snake in two of these trials was quite different from that seen in the Indian setting limiting generalization of these findings. Hence, home-grown evidence is needed to persuade clinicians to use antibiotics rationally.
详细描述
Snake bite is a common clinical problem in India and elsewhere, affecting agricultural workers and rural population, resulting in thousands of deaths every year. Apart from causing systemic manifestations such as coagulopathy, acute renal failure, and neuroparalysis, local effects of the venom manifest as swelling of the bitten limb. Despite administration of adequate antivenom, the limb swelling progresses in the first 48-72 hours accompanied by considerable pain. Often the limb swelling is accompanied by formation of blebs and gangrenous skin changes. At times, the limb swelling is severe enough to result in compartment syndrome, necessitating surgical interventions such as fasciotomy and debridement. Animal bites are typically associated with a risk of infection by the oral flora. Likewise, apart from releasing the venom, inoculation of oral flora as a result of snake bite could result in local infectious complications adding to the deleterious effects of the snake venom.
Observational studies suggest that the risk of infection following simple bites on the lower limbs is much less than what is often believed, and evidence from clinical trials also does not support routine use of antibiotics in snake bite. For this reason, clinical practice guidelines do not recommend routine prophylactic use of antibiotics in snake bite. But, in reality, many clinicians continue to use antibiotics routinely in all venomous snake bites hoping to prevent a local infection. While such a strategy may not reduce the risk of infection, it would result in overuse of antibiotics promoting antimicrobial resistance and escalating treatment costs.
The investigators hypothesize that clinically-directed use of antibiotics would be non-inferior to routine use in preventing local infectious complications of snake bite, while being superior in reducing the antibiotic consumption. Non-inferiority would be inferred if the one-sided 95% CI of the difference does not exceed 10% in favour of the routine use arm.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-65 years
- •History of snake bite with features of local envenomation with/without systemic features
- •Less than 24 hours since bite, AND
- •No prior antibiotic treatment
排除标准
- •Upper limb bites
- •Multiple (> 1) bites
- •Wound manipulation
- •Extensive local necrosis or blebs
- •Seriously-ill patients with hypotension/capillary leak/life threatening bleeding.
- •Suspected cobra bite, OR
- •Pregnant/breast-feeding women
研究组 & 干预措施
Routine use arm
All participants allocated to this arm will be given
- Injection Tetanus toxoid 0.5 ml intramuscularly Stat
- Antibiotic (Co-amoxiclav) will be given to all patients for a minimum duration of 5 days.
- Daily clinical assessment would be done. Change of antibiotics is allowed if clinical failure occurs.
Use of antibiotics for emergent indications unrelated to the bitten limb such as nosocomial infections would be allowed at the treating physician's discretion.
干预措施: Co-amoxiclav (Drug)
Routine use arm
All participants allocated to this arm will be given
- Injection Tetanus toxoid 0.5 ml intramuscularly Stat
- Antibiotic (Co-amoxiclav) will be given to all patients for a minimum duration of 5 days.
- Daily clinical assessment would be done. Change of antibiotics is allowed if clinical failure occurs.
Use of antibiotics for emergent indications unrelated to the bitten limb such as nosocomial infections would be allowed at the treating physician's discretion.
干预措施: Tetanus toxoid (Biological)
Clinically-directed use arm
Participants allocated to this arm will be given
- Injection Tetanus toxoid 0.5 ml intramuscularly Stat
- Daily clinical assessment would be done. Antibiotic (Co-amoxiclav) will be started only if clinical failure occurs.
Use of antibiotics for emergent indications unrelated to the bitten limb such as nosocomial infections would be allowed at the treating physician's discretion.
干预措施: Co-amoxiclav (Drug)
Clinically-directed use arm
Participants allocated to this arm will be given
- Injection Tetanus toxoid 0.5 ml intramuscularly Stat
- Daily clinical assessment would be done. Antibiotic (Co-amoxiclav) will be started only if clinical failure occurs.
Use of antibiotics for emergent indications unrelated to the bitten limb such as nosocomial infections would be allowed at the treating physician's discretion.
干预措施: Tetanus toxoid (Biological)
结局指标
主要结局
Clinical failure
时间窗: up to 4 weeks
Defined as occurrence of any one of the following on daily assessments - Abscess formation at any point of time; Surgical debridement/fasciotomy at any time; Worsening limb swelling beyond 72-96 hours or appearance of necrosis or blebs along with any one of the following: fever, persistent or worsening leucocytosis, or global deterioration on clinical assessment.
Antibiotic consumption
时间窗: up to 4 weeks
Defined as the total amount of all antibiotics consumed regardless of clinical indication expressed in terms of defined daily doses (DDD).
次要结局
- Anti-snake venom consumption(up to 4 weeks)
- New-onset organ failure(up to 4 weeks)
- Death/need for surgical intervention(up to 4 weeks)
- Drug-related adverse events(up to 4 weeks)
- Length of hospital stay(up to 4 weeks)
研究者
Tamilarasu Kadhiravan, MD
Professor of Medicine
Jawaharlal Institute of Postgraduate Medical Education & Research