AzTrials
AzTrials

Snake BitePhase 2NCT01284855

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

A Phase 2 study testing Antivenom in people with Snake Bite, run by CTU at 3 sites in Nepal.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 5 years and older
Conditions the study is for
Snake Bite
What is being tested?
Antivenom
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
250 participants
Where
3 sitesNepal
Study dates
Apr 2011to 20 Mar 2013
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 5 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

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

Who cannot join

  • 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
Show all 9Show fewer
  • Patients with pre-existing neurological or muscular disorders
  • Subjects with known history of allergy to horse proteins
  • Patients with proven viper bites

Trial locations and contacts

3 sites in 1 country.

Nepal3 sites
  • Bharatpur Hospital

    Bharatpur, Chitwan

  • Charali snake bite treatment centre

    Charali, Jhapa

  • Damak red cross center

    Damak, Jhapa

Other trials in Nepal

About this study

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

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.

Read the 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.

Conditions
Snake Bite
Being tested
Antivenom
Keywords
neurotoxic envenoming (WHO ICD-10 T63.0)
Medical subject headings
Snake Bites

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AntivenomDrug

    Also called VINS Bioproduct

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

Study groups in NCT01284855
Study groupRoleWhat they receive
Low initial doseActive comparatorThis 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
Receives: Drug: Antivenom
High initial doseExperimentalThis 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
Receives: Drug: Antivenom

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

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

  2. Number of patients with a Serious Adverse Events

    Measured: Last follow-up visit (6 months after randomization)

Secondary outcomes (7)
  1. Mortality

    Number of deaths

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

  2. Total amount of antivenom administered

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

  3. Time to recovery

    Time between admission to the health centre and the disappearance of all neurotoxic sign s

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

  4. Total cost of treatment

    Including direct (antivenom and other drugs costs, costs of hospitalization, and costs of Adverse Events management)and indirect costs (working days missed)

    Measured: Last follow-up visit (6 months after randomization)

  5. Number of patients with Adverse Events

    Measured: Last follow-up visit (6 months after randomization)

  6. Number of patients who needed assisted ventilation during hospitalization

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

  7. Number of patients who showed a worsening of neurotoxicity during hospitalization

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2011 (estimated)
  2. Study startApr 2011
  3. Primary completion15 Oct 2012
  4. Study completion20 Mar 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
250 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01284855
Sponsor's protocol ID
CER 08-192
Other IDs
SNF IZ70Z0 - 131 223
Status last verified
Feb 2017
First submitted
25 Jan 2011
Last updated
7 Feb 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 31205473
  • 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.

    PubMed 28510574

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Antivenom in people with Snake Bite, run by CTU at 3 sites in Nepal.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Nepal. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01284855, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2017.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in