A Phase 4 interventional study of Co-amoxiclav and Tetanus toxoid in Snake Bites, sponsored by Jawaharlal Institute of Postgraduate Medical Education & Research. Terminated at 1 site in India. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2025-05-30.
Sponsored by Jawaharlal Institute of Postgraduate Medical Education & Research · Phase 4, Interventional, and Treatment
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.
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.
Exclusion Criteria:
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.
Drug: Co-amoxiclav · Biological: Tetanus toxoid
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.
Drug: Co-amoxiclav · Biological: Tetanus toxoid
Injection Co-amoxiclav 1.2 g intravenously q8h for a minimum of 48-72 hours; switched to oral Co-amoxiclav 625 mg b.i.d. when clinically appropriate.
Also known as: Augmentin
Injection Tetanus toxoid 0.5 ml intramuscularly Stat
Clinical failure
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.
Time frame: up to 4 weeks
Antibiotic consumption
Defined as the total amount of all antibiotics consumed regardless of clinical indication expressed in terms of defined daily doses (DDD).
Time frame: up to 4 weeks
Length of hospital stay
Number of days from hospital admission until discharge
Time frame: up to 4 weeks
Anti-snake venom consumption
The total number of vials of the anti-venom administered including doses received prior to being brought to JIPMER.
Time frame: up to 4 weeks
New-onset organ failure
This includes acute kidney injury (AKI) defined as peak serum creatinine \> 2 mg/dL, shock defined as systolic blood pressure \< 90 mm Hg requiring use of vasopressors; bleeding from any site necessitating transfusion of blood/blood products; and capillary leak syndrome.
Time frame: up to 4 weeks
Death/need for surgical intervention
This would be a composite measure of death and/or need for surgical intervention. Death indicates in-hospital death due to any cause during the index hospitalisation. Surgical intervention would include need for any surgical intervention such as incision and drainage of abscess, wound debridement for necrosis or gangrene, fasciotomy for compartment syndrome, etc.
Time frame: up to 4 weeks
Drug-related adverse events
Any suspected or confirmed adverse drug reaction
Time frame: up to 4 weeks
Plan to share: Yes — De-identified individual participant data that underlie the published results (text, tables, figures and appendices).
Supporting information: Study protocol, Icf, Csr
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Jawaharlal Institute of Postgraduate Medical Education & Research