Clinical trial NCT02570347: Routine Antibiotic vs. Directed Antibiotic Treatment in Snake Bite
Official title: Routine vs. Clinically-Directed Antibiotic Treatment in Snake Bite With Local Envenomation: a Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Snake Bites
Keywords: Snake Envenomation
Antibiotic Prophylaxis
Viperidae
Lead sponsor: Jawaharlal Institute of Postgraduate Medical Education & Research
Sponsor class: OTHER_GOV
First posted: 2015-10-07
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Clinical failure
timeFrame: up to 4 weeks
measure: Antibiotic consumption
timeFrame: up to 4 weeks
Secondary outcomes:
measure: Length of hospital stay
timeFrame: up to 4 weeks
measure: Anti-snake venom consumption
timeFrame: up to 4 weeks
measure: New-onset organ failure
timeFrame: up to 4 weeks
measure: Death/need for surgical intervention
timeFrame: up to 4 weeks
measure: Drug-related adverse events
timeFrame: up to 4 weeks
Other outcomes:
Locations:
city: Pondicherry
country: India
facility: Department of Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research
state: Puducherry
Study officials:
affiliation: Jawaharlal Institute of Postgraduate Medical Education & Research
name: Tamilarasu Kadhiravan, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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