Routine Antibiotic vs. Directed Antibiotic Treatment in Snake Bite

Phase 4

Terminated

• Conditions: Snake Bites
• Interventions: Drug: Co-amoxiclav; Biological: Tetanus toxoid

• Registration Number: NCT02570347
• Lead Sponsor: Jawaharlal Institute of Postgraduate Medical Education & Research

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.

Study Timeline

• Study First Submitted: 2015-10-05
• Study First Submitted QC: 2015-10-05
• Study First Posted: 2015-10-07
• Study Start: 2016-05-03
• Primary Completion: 2019-10-24
• Study Completion: 2020-03-31
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-24
• Last Update Posted: 2025-05-30

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 66

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Routine use arm	Tetanus toxoid	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.
Clinically-directed use arm	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.
Routine use arm	Co-amoxiclav	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.
Clinically-directed use arm	Co-amoxiclav	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.

Primary Outcome Measures

Name	Time	Method
Clinical failure	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	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).

Secondary Outcome Measures

Name	Time	Method
Anti-snake venom consumption	up to 4 weeks	The total number of vials of the anti-venom administered including doses received prior to being brought to JIPMER.
New-onset organ failure	up to 4 weeks	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.
Death/need for surgical intervention	up to 4 weeks	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.
Drug-related adverse events	up to 4 weeks	Any suspected or confirmed adverse drug reaction
Length of hospital stay	up to 4 weeks	Number of days from hospital admission until discharge

Trial Locations

Locations (1)

Department of Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research; 🇮🇳 Pondicherry, Puducherry, India