Routine Antibiotic vs. Directed Antibiotic Treatment in Snake Bite

NCT02570347 | Terminated Phase 4

• 1 other identifier: JIP/IEC/2015/17/649
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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.

Conditions

Snake Bites

Keywords

Snake Envenomation; Antibiotic Prophylaxis; Viperidae

Outcome Measures

Primary Outcomes (2)

• 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.

  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).

  up to 4 weeks

Secondary Outcomes (5)

• Length of hospital stay

  up to 4 weeks

• 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

Study Arms (2)

Routine use arm

ACTIVE COMPARATOR

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

Clinically-directed use arm

EXPERIMENTAL

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

Interventions

Co-amoxiclav DRUG

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

Clinically-directed use arm; Routine use arm

Tetanus toxoid BIOLOGICAL

Injection Tetanus toxoid 0.5 ml intramuscularly Stat

Clinically-directed use arm; Routine use arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jawaharlal Institute of Postgraduate Medical Education & Research: lead

Study Sites (1)

Department of Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research

Puducherry, Puducherry, 605006, India

Location

Related Publications (7)

• Terry P, Mackway-Jones K. Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. The use of antibiotics in venomous snake bite. Emerg Med J. 2002 Jan;19(1):48-9. doi: 10.1136/emj.19.1.48.

  PMID: 11777875 BACKGROUND

• Terry P, Mackway-Jones K. Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Antibiotics in non-venomous snakebite. Emerg Med J. 2002 Mar;19(2):142. doi: 10.1136/emj.19.2.142.

  PMID: 11904264 BACKGROUND

• Jorge MT, Malaque C, Ribeiro LA, Fan HW, Cardoso JL, Nishioka SA, Sano-Martins IS, Franca FO, Kamiguti AS, Theakston RD, Warrell DA. Failure of chloramphenicol prophylaxis to reduce the frequency of abscess formation as a complication of envenoming by Bothrops snakes in Brazil: a double-blind randomized controlled trial. Trans R Soc Trop Med Hyg. 2004 Sep;98(9):529-34. doi: 10.1016/j.trstmh.2003.12.009.

  PMID: 15251401 BACKGROUND

• Kularatne SA, Kumarasiri PV, Pushpakumara SK, Dissanayaka WP, Ariyasena H, Gawarammana IB, Senanayake N. Routine antibiotic therapy in the management of the local inflammatory swelling in venomous snakebites: results of a placebo-controlled study. Ceylon Med J. 2005 Dec;50(4):151-5. doi: 10.4038/cmj.v50i4.1405.

  PMID: 16538909 BACKGROUND

• Kerrigan KR, Mertz BL, Nelson SJ, Dye JD. Antibiotic prophylaxis for pit viper envenomation: prospective, controlled trial. World J Surg. 1997 May;21(4):369-72; discussion 372-3. doi: 10.1007/pl00012255.

  PMID: 9143566 BACKGROUND

• Mohapatra B, Warrell DA, Suraweera W, Bhatia P, Dhingra N, Jotkar RM, Rodriguez PS, Mishra K, Whitaker R, Jha P; Million Death Study Collaborators. Snakebite mortality in India: a nationally representative mortality survey. PLoS Negl Trop Dis. 2011 Apr 12;5(4):e1018. doi: 10.1371/journal.pntd.0001018.

  PMID: 21532748 BACKGROUND

• Gautam A, Indu MB, Bhardwaj A, Sabitha P, Deepanjali S, Suryanarayana BS, Bammigatti C, Kadhiravan T. Clinically directed initiation versus routine use of amoxicillin-clavulanate and the risk of local complications among patients with haemotoxic snakebite envenomation treated at a teaching hospital in southern India: a randomised, non-inferiority trial. BMJ Open. 2025 Jun 23;15(6):e094409. doi: 10.1136/bmjopen-2024-094409.

  PMID: 40550712 DERIVED

MeSH Terms

Conditions

Snake Bites

Interventions

Amoxicillin-Potassium Clavulanate Combination; Tetanus Toxoid

Condition Hierarchy (Ancestors)

Bites and Stings; Poisoning; Chemically-Induced Disorders; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Clavulanic Acid; Clavulanic Acids; beta-Lactams; Lactams; Amides; Organic Chemicals; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Toxoids; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Tamilarasu Kadhiravan, M.D.

  Jawaharlal Institute of Postgraduate Medical Education & Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: October 5, 2015
• First Posted: October 7, 2015
• Study Start: May 3, 2016
• Primary Completion: October 24, 2019
• Study Completion: March 31, 2020
• Last Updated: May 30, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: Immediately following publication for up to 5 years.
• Access Criteria: Anyone who wishes to access the data, upon reasonable request to the principal investigator.

Locations

IN (1)