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Comparison of Two Dose Regimens of Snake Antivenom for the Treatment of Snake Bites Envenoming in Nepal

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
CTU, University Hospital, Geneva
ClinicalTrials.gov Identifier:
NCT01284855
First received: January 25, 2011
Last updated: December 12, 2012
Last verified: December 2012
  Purpose

This study aims at comparing two doses of antivenom in the treatment of snake bite envenoming. It will take place in 3 centers in rural Nepal and will involve 250 snake bite victims presenting with one or more sign of neurotoxic envenoming. The objective of the study is to generate enough scientific evidence to improve Nepal's current national guidelines for the management of snake bites.


Condition Intervention Phase
Snake Bite
Drug: Antivenom
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Clinical Trial of Two Dose Regimens of VINS Polyvalent Antivenom (ATC J06AA03) for the Treatment of Snake Bites With Neurotoxic Envenoming in Nepal

Further study details as provided by University Hospital, Geneva:

Primary Outcome Measures:
  • Composite endpoint: Number of patients who either 1) died, or 2) needed assisted ventilation, or 3) showed a worsening of envenoming signs during hospital stay [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 5 days ] [ Designated as safety issue: No ]

    The endpoint is composite and includes the number of patients who

    • die during hospitalization
    • are put under assisted ventilation during hospitalization
    • necessitate additional doses of antivenom because of a worsening of neurotoxicity.

    A worsening of neurotoxicity will be defined as the appearance of 2 new neurotoxic signs OR the appearance of a severe neurotoxic sign (i.e. loss of gag reflex or paradoxical breathing)


  • Number of patients with a Serious Adverse Events [ Time Frame: Last follow-up visit (6 months after randomization) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Mortality [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 5 days ] [ Designated as safety issue: No ]
    Number of deaths

  • Total amount of antivenom administered [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 5 days ] [ Designated as safety issue: No ]
  • Time to recovery [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 5 days ] [ Designated as safety issue: No ]
    Time between admission to the health centre and the disappearance of all neurotoxic sign s

  • Total cost of treatment [ Time Frame: Last follow-up visit (6 months after randomization) ] [ Designated as safety issue: No ]
    Including direct (antivenom and other drugs costs, costs of hospitalization, and costs of Adverse Events management)and indirect costs (working days missed)

  • Number of patients with Adverse Events [ Time Frame: Last follow-up visit (6 months after randomization) ] [ Designated as safety issue: Yes ]
  • Number of patients who needed assisted ventilation during hospitalization [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 5 days ] [ Designated as safety issue: No ]
  • Number of patients who showed a worsening of neurotoxicity during hospitalization [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 5 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 250
Study Start Date: April 2011
Estimated Study Completion Date: April 2013
Estimated Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Low initial dose
This arms corresponds to Nepal national protocol and involves the initial administration of 2 vials of antivenom over one hour followed by the slow infusion of 4 vials over 4 hours
Drug: Antivenom
Polyvalent antivenom directed against Indian spectacled cobra (N. naja), common Indian krait (B. caeruleus), saw-scaled viper (Echis carinatus) and Russell's viper.
Other Name: VINS Bioproduct
Experimental: High initial dose
This arms corresponds to Indian national protocol and involves the initial administration of 10 vials of antivenom over one hour followed by the slow infusion of saline over 4 hours
Drug: Antivenom
Polyvalent antivenom directed against Indian spectacled cobra (N. naja), common Indian krait (B. caeruleus), saw-scaled viper (Echis carinatus) and Russell's viper.
Other Name: VINS Bioproduct

Detailed Description:

Snake bites are considered as one of the major neglected public health issues of tropical areas. They occur chiefly in developing countries and mainly affect poor rural communities. Besides the inadequate supply, distribution and accessibility of antivenom, a major problem is the absence of standardized and adequate treatment protocol. There is a significant diversity in clinical practices, in particular concerning the dose of antivenom given. Additionally, antivenom is often given even in the absence of a clear indication for envenoming. Altogether, this leads to an incredible waste of a scarce and costly resource.

In Nepal there are gross disparities in the management and outcomes of snake bite envenoming. The country's national guidelines, issued in 2004, prescribe an initial antivenom dose that is 5 times less than the one advocated by most experts. The dosage recommended by the National guidelines is not based on scientific or clinical evidence, and currently, there is confusion about the adequate dose to be administered. Some physicians follow recommendations published by experts, others follow the National guidelines, but for most, dosage is arbitrary. These discrepancies directly impact on morbidity and mortality and lead to wastage of a costly treatment that few can afford.

The principal objective of the study is to establish unequivocally which dosage regimen is the most appropriate for the treatment of snake bite neurotoxic envenoming. It is a randomized, double-blind, clinical trial comparing high and low initial doses of snake polyvalent antivenom also known as Anti Snake Venom Serum (ASVS). 250 snake bite victims showing signs of neurotoxic envenoming will be enrolled over 2 years in three health centres of Southern Nepal. Each participant will initially receive either 2 vials or 10 vials of snake polyvalent antivenom. Mortality, the proportion of patients needing assisted respiration, and the percentage of patients who show worsening of neurotoxic signs and therefore require additional doses of antivenom will be compared in both arms. The kinetics of recovery and the total consumption of antivenom will also be compared. Finally, the incidence and severity of early and late adverse reactions to antivenom will be assessed. The economical impact of snake bite envenoming will also be determined by measuring direct and indirect costs to both health services and individual victims. Because they chiefly affect agricultural workers and children, snake bites have serious economic consequences, a fact that is frequently overlooked by national authorities.

  Eligibility

Ages Eligible for Study:   5 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • History of snake bite; AND
  • Age ≥ 5 years; AND
  • Informed consent obtained; AND
  • Showing one or more signs of neurotoxic envenoming

Exclusion Criteria:

  • Subject unlikely to co-operate in the study
  • Pregnant or breastfeeding women
  • Patients presenting more than 24 hours after the bite
  • Patients requiring ventilation support at the time of presentation
  • Subjects with previous history of snake bite with envenoming
  • Patients who already received antivenom before presenting to the study centre
  • Patients with pre-existing neurological or muscular disorders
  • Subjects with known history of allergy to horse proteins
  • Patients with proven viper bites
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01284855

Locations
Nepal
Bharatpur Hospital
Bharatpur, Chitwan, Nepal
Charali snake bite treatment centre
Charali, Jhapa, Nepal
Damak red cross center
Damak, Jhapa, Nepal
Sponsors and Collaborators
CTU
Investigators
Principal Investigator: Sanjib Sharma, MD B. P. K. I. H. S.
Study Director: François Chappuis, MD, PhD University Hospital, Geneva
Study Chair: David Warrell, MD, PhD University of Oxford
  More Information

No publications provided

Responsible Party: CTU, University Hospital, Geneva
ClinicalTrials.gov Identifier: NCT01284855     History of Changes
Other Study ID Numbers: CER 08-192, SNF IZ70Z0 - 131 223
Study First Received: January 25, 2011
Last Updated: December 12, 2012
Health Authority: Nepal: Nepal Health Research Council (NHRC)

Keywords provided by University Hospital, Geneva:
neurotoxic envenoming (WHO ICD-10 T63.0)

Additional relevant MeSH terms:
Snake Bites
Bites and Stings
Chemically-Induced Disorders
Poisoning
Wounds and Injuries
Antivenins
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014