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

NCT01284855 | Completed Phase 2 DMC

• 2 other identifiers: CER 08-192SNF IZ70Z0 - 131 223
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Snake Bite

Keywords

neurotoxic envenoming (WHO ICD-10 T63.0)

Outcome Measures

Primary Outcomes (2)

• 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

  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)

  Participants will be followed for the duration of hospital stay, an expected average of 5 days

• Number of patients with a Serious Adverse Events

  Last follow-up visit (6 months after randomization)

Secondary Outcomes (7)

• Mortality

  Participants will be followed for the duration of hospital stay, an expected average of 5 days

• Total amount of antivenom administered

  Participants will be followed for the duration of hospital stay, an expected average of 5 days

• Time to recovery

  Participants will be followed for the duration of hospital stay, an expected average of 5 days

• Total cost of treatment

  Last follow-up visit (6 months after randomization)

• Number of patients with Adverse Events

  Last follow-up visit (6 months after randomization)

Study Arms (2)

Low initial dose

ACTIVE COMPARATOR

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

High initial dose

EXPERIMENTAL

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

Interventions

Antivenom DRUG

Polyvalent antivenom directed against Indian spectacled cobra (N. naja), common Indian krait (B. caeruleus), saw-scaled viper (Echis carinatus) and Russell's viper.

Also known as: VINS Bioproduct

High initial dose; Low initial dose

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• CTU: lead

Study Sites (3)

Bharatpur Hospital

Bharatpur, Chitwan, Nepal

Location

Charali snake bite treatment centre

Charali, Jhapa, Nepal

Location

Damak red cross center

Damak, Jhapa, Nepal

Location

Related Publications (2)

• Sharma SK, Alirol E, Ghimire A, Shrestha S, Jha R, Parajuli SB, Shrestha D, Shrestha SJ, Bista A, Warrell D, Kuch U, Chappuis F, Taylor WRJ. Acute Severe Anaphylaxis in Nepali Patients with Neurotoxic Snakebite Envenoming Treated with the VINS Polyvalent Antivenom. J Trop Med. 2019 May 2;2019:2689171. doi: 10.1155/2019/2689171. eCollection 2019.

  PMID: 31205473 DERIVED

• Alirol E, Sharma SK, Ghimire A, Poncet A, Combescure C, Thapa C, Paudel VP, Adhikary K, Taylor WR, Warrell D, Kuch U, Chappuis F. Dose of antivenom for the treatment of snakebite with neurotoxic envenoming: Evidence from a randomised controlled trial in Nepal. PLoS Negl Trop Dis. 2017 May 16;11(5):e0005612. doi: 10.1371/journal.pntd.0005612. eCollection 2017 May.

  PMID: 28510574 DERIVED

MeSH Terms

Conditions

Snake Bites

Interventions

Antivenins

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antitoxins; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Study Officials

• Sanjib Sharma, MD

  B. P. K. I. H. S.

  PRINCIPAL INVESTIGATOR

• François Chappuis, MD, PhD

  University Hospital, Geneva

  STUDY DIRECTOR

• David Warrell, MD, PhD

  University of Oxford

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: CTU

Study Record Dates

• First Submitted: January 25, 2011
• First Posted: January 27, 2011
• Study Start: April 1, 2011
• Primary Completion: October 15, 2012
• Study Completion: March 20, 2013
• Last Updated: February 7, 2017

Record last verified: 2017-02

Locations

NE (3)