Routine Antibiotic vs. Directed Antibiotic Treatment in Snake Bite

Snake Bites Clinical Trial

— RADIANS  

Official title:

Routine vs. Clinically-Directed Antibiotic Treatment in Snake Bite With Local Envenomation: a Randomised Controlled Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02570347
• Other study ID #: JIP/IEC/2015/17/649
• Status: Terminated
• Phase: Phase 4
• Start date: May 3, 2016
• Est. completion date: March 31, 2020

Study information

• Verified date: April 2024
• Source: Jawaharlal Institute of Postgraduate Medical Education & Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 66
• Est. completion date: March 31, 2020
• Est. primary completion date: October 24, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Snake Bites

Intervention

Drug:
• Co-amoxiclav
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.

Biological:
• Tetanus toxoid
Injection Tetanus toxoid 0.5 ml intramuscularly Stat

Locations

Country	Name	City	State
India	Department of Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research	Pondicherry	Puducherry

Sponsors (1)

Lead Sponsor	Collaborator
Jawaharlal Institute of Postgraduate Medical Education & Research

Country where clinical trial is conducted

India, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Length of hospital stay	Number of days from hospital admission until discharge	up to 4 weeks
Secondary	Anti-snake venom consumption	The total number of vials of the anti-venom administered including doses received prior to being brought to JIPMER.	up to 4 weeks
Secondary	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.	up to 4 weeks
Secondary	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.	up to 4 weeks
Secondary	Drug-related adverse events	Any suspected or confirmed adverse drug reaction	up to 4 weeks