Skip to main content
OpenTrials
Not Yet Recruiting

NCT Number: NCT07500233

Trial of Oral Community SVMP INhibitors for Snakebite

Bites by venomous snakes can cause disability and can be life-threatening. We are doing research in adult patients to try and find medications that can be administered orally and can help to reduce disability and death due to snakebite. We do not know whether the drugs in this study work in humans and we aim to discover this.

In Stage A, we will provide a new drug or placebo (inactive medication) in community locations, such as rural health clinics, in Brazil and Ghana. Neither the patient nor the clinical team will know which treatment option has been allocated. If a drug were to show signs of working as a treatment during Stage A, it will progress to Stage B. In Stage B, we will provide the drug or antivenom (the current approved treatment for snakebite) in a hospital setting. During Stage B, the patient and the clinician will know which treatment has been received. The purpose of Stage B is to discover whether the drug might hold promise as an alternative treatment to antivenom in the future. Participants will be monitored closely during Stage B and 'rescue antivenom' will be given if they become unwell.

The medications being considered were developed for other health conditions, like cancer, so have been given to patients across the world before. The medications may prove effective at inhibiting the damaging effects of snake venom. Each of the trial drugs could be taken by mouth (oral) in community clinics and ambulances, much sooner than the current treatment for snakebite injuries (antivenom), which is only given within hospitals. They may have other advantages too, like reduced cost and less chance of side effects, including severe allergic reaction. Before a medication is included in the trial it will be reviewed and approved by a group of experts. Before a medication is included in Stage B of the trial it will be reviewed for whether it is safe and effective enough (from Stage A results) to be compared against antivenom.

Stage A Participants will be recruited in the field when they attend a community clinic or ambulance. They will be randomly assigned to receive either a study drug or a placebo. When they arrive at hospital, all participants will receive standard of care antivenom. Participants will continue to take study medication (or matching placebo) for 24 hours, and have frequent blood samples collected during their treatment. Once 20 participants have received the drug and twenty have received the placebo, recruitment for this drug will cease. The difference in the improvement in blood clotting studies (how long it takes to clot) will be compared between the participants receiving the drug and the placebo. If the drug shows an improvement in the clotting studies, then it will proceed to Stage B. If the drug fails to improve the clotting studies, or if it is found to cause unsafe side effects, then it will be rejected from progressing to Stage B.

Stage B Participants will be recruited upon arrival at the hospital site and randomly assigned to receive either a study drug shown to be effective in Stage A or standard-of-care antivenom. Study drugs will be administered for 24 hours, during which all participants will undergo frequent blood sampling. Recruitment for each study drug will stop once 48 participants have received the drug and 48 have received antivenom. The primary comparison will be the improvement in blood clotting parameters between the intervention and control groups. If the study drug is safe and achieves a similar improvement to antivenom - allowing for up to a three-hour delay in effect due to oral absorption compared with intravenous antivenom - it will be considered a promising alternative therapy.

Following a planned 3-day stay in hospital, all participants from Stage A and B will be followed up at 2 and 6 weeks. These follow-up visits can be conducted by telephone, outpatient hospital visit, or home visit, depending on what is most suitable for that individual. The end of study visit will take place at the 6-week visit.

Not Yet Recruiting

Trial opening soon.

Get Notified

Key information

Conditions

Snakebite Bites and Stings Chemically-Induced Disorders Poisoning Snake Bites Wounds and Injuries

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Snakebite in the preceding 12 hours (Stage A & B)
  • Aged ≥18-years (Stage A & B)
  • Residing in the Amazonas region of Brazil or the Upper West region of Ghana (Stage A & B)
  • Capable of giving informed consent (Stage A & B)
  • Are eligible for antivenom treatment according to local guidelines (Stage B only)

Exclusion criteria

  • individual with severe envenoming (defined in the protocol) (Stage A & B)
  • concomitant anticoagulation (heparins, coumarin anticoagulants such as warfarin, or direct oral anticoagulants such as apixaban) (Stage A & B)
  • pregnant or breastfeeding (Stage A & B)

Treatment and study plan

2,3-dimercapto-1-propanesulfonic acid

Drug

Oral administration

Other names: unithiol, DMPS

marimastat

Drug

oral administration

Oral placebo capsules

Drug

Oral placebo

Antivenom Snakes

Drug

Standard of care IV antivenom recommended in country

Primary outcomes

  1. Mean time until lab INR is less than 50% of the baseline value (efficacy)

    Time frame: From randomisation until end of admission

    Stage A and B - The mean time until the lab INR is <50% of the baseline value (or less than 1.4 if the baseline value is <2.8) on two consecutive measurements per treatment arm. Time is measured starting from randomisation. Time is measured until the first of the two consecutive measurements being <50% or <1.4. Baseline INR sample is defined as blood collected day 0 post-consent and prior to treatment administration.

  2. Incidence (cumulative) of safety events (safety)

    Time frame: From informed consent until 42 days after randomisation

    Stage A and B- Incidence (cumulative) of any AE, non-serious AE, SAE, SAR, SUSAR. Cumulative incidence is calculated as the number (%) of participants who experience at least one AE in the pre-specified groups.

Secondary outcomes

  1. Stage A- Assess the effect of pre-hospital treatment on INR improvement based on travel time to hospital.

    Time frame: Day 0 clinic and hospital

    Stage A- Assess the effect of pre-hospital treatment on INR improvement based on travel time to hospital. Amongst participants with baseline INR ≥1.4, the log change in INR, from pre-hospital baseline to hospital arrival, will be analysed using a linear regression model with treatment group, travel time, and their interaction

  2. Stage A- Assess the effect of pre-hospital treatment on fibrinogen improvement based on travel time to hospital.

    Time frame: Day 0 clinic and hospital

    Stage A- Assess the effect of pre-hospital treatment on fibrinogen improvement based on travel time to hospital. Amongst participants with baseline INR ≥1.4, the log change in fibrinogen from pre-hospital baseline to 12 hours after randomisation, will be analysed using a linear regression model with treatment group, travel time, and their interaction.

  3. Stage A and B- To determine the acceptability of the intervention between treatment arms in terms of quality of life.

    Time frame: Day 14, Day 42 (Stage A and B)

    Stage A and B- to determine the acceptability of the intervention between treatment arms as a patient-reported outcome of functioning. Assessed using the WHO Disability Assessment Schedule 2.0 (WHODAS 2.0), a 12-item validated scale measuring disability across six life domains (cognition, mobility, self-care, interpersonal interaction, life activities, and participation). Scores range from 0 to 48, where higher scores indicate greater disability.

    Unit of Measure: Units on a scale (0-48)

  4. Stage A and B- To determine the acceptability of the intervention between treatment arms as patient-reported outcomes of functioning.

    Time frame: Day 14 and Day 42 post-randomisation (Stage A and B)

    Assessed using the Patient Specific Functional Scale (PSFS), in which participants rate their ability to perform up to three self-nominated activities on a numerical scale from 0 to 10, where 0 indicates inability to perform the activity and 10 indicates full pre-injury ability. Higher scores indicate better function. Unit of Measure: Units on a scale (0-10).

  5. Stage A and B- To evaluate the reach of the intervention (Participant refusal rate)

    Time frame: Day 0 clinic (Stage A) or hospital (Stage B)

    Stage A and B- To evaluate the reach of the intervention. Monitor enrolment data based on % refusal.

    Measurement: Percentage of eligible patients who decline participation Unit of measure: Percentage (%)

  6. Stage A and B- To evaluate the reach of the intervention (Exclusion rate)

    Time frame: Day 0 clinic (Stage A) or hospital (Stage B)

    Stage A and B- To evaluate the reach of the intervention. Monitor enrolment data based on % exclusion.

    Measurement: Percentage of screened patients excluded due to protocol-defined exclusion criteria.

    Unit of measure: Percentage (%)

  7. Stage A and B- To evaluate the reach of the intervention (Time between bite and treatment received)

    Time frame: Day 0 clinic (Stage A) or hospital (Stage B)

    Stage A and B- To evaluate the reach of the intervention. Monitor enrolment data based on time between bite and treatment received.

    Measurement: Time elapsed between reported snakebite and receipt of study treatment.

    Unit of measure: Hours

  8. Stage A and B-To evaluate the reach of the intervention based on recruitment rate across the study catchment area (Recruitment rate)

    Time frame: Day 0 clinic (Stage A) or hospital (Stage B)

    Stage A and B- To evaluate the reach of the intervention. Monitor enrolment data based recruitment rate across the study catchment area.

    Measurement: Rate of participant enrolment across the study catchment area. Unit of measure: Participants per site per month

  9. Stage A and B- Identify benefits of and barriers for future implementation of the intervention.

    Time frame: Day 42

    Stage A and B- Identify benefits of and barriers for future implementation of the intervention. Mixed-methods following the Consolidated Framework Implementation Research interviewing participants and health care providers

  10. Stage A- To determine differences in resolution of clinically relevant non-serious bleeding events.

    Time frame: Day 0 clinic and hospital

    Stage A- To determine differences in resolution of clinically relevant non-serious bleeding events. Amongst all participants with non-major bleeding (epistaxis, gingival bleeding, or bleeding from a venepuncture site for >5 min) at randomisation, proportion with cessation of bleeding on arrival to the hospital site per treatment arm.

  11. Stage B- Assess the effect of time to treatment on INR improvement (based on estimated time from bite until administration of the treatment).

    Time frame: Day 0 hospital

    Stage B- Assess the effect of time to treatment on INR improvement (based on estimated time from bite until administration of the treatment). Amongst participants with baseline INR ≥1.4, change in INR from baseline to 6 hours, analysed using a linear regression model with treatment group, estimated time from bite to treatment, and their interaction

  12. Stage B- Assess the effect of time to treatment on fibrinogen improvement (based on estimated time from bite until administration of the treatment).

    Time frame: Day 0 hospital

    Stage B- Assess the effect of time to treatment on fibrinogen improvement (based on estimated time from bite until administration of the treatment). Amongst participants with baseline INR ≥1.4, change in fibrinogen from baseline to 12 hours, analysed using a linear regression model with treatment group, estimated time from bite to treatment, and their interaction

  13. Stage B- To determine differences in resolution of clinically relevant non-serious bleeding events.

    Time frame: Day 0 hospital

    Stage B- To determine differences in resolution of clinically relevant non-serious bleeding events. Amongst all participants with non-major bleeding (epistaxis, gingival bleeding, or bleeding from a venepuncture site for >5 min) at randomisation, proportion with cessation of bleeding at 3 hours after randomisation per treatment arm.

Study contacts

Contact information is provided by the study sponsor or research team.

TOCSINS Trial Management

CONTACT

[email protected]

+44(0)1517053100

Sponsors and collaborators

Lead sponsor

Liverpool School of Tropical Medicine

Other

Collaborators

  • Coefficient Giving (Formerly Open Philanthropy)
  • Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
  • Kumasi Centre for Collaborative Research (KCCR)

Registry information

Official study title

A Phase 2 Randomised Placebo-controlled Platform Trial of Snake Venom Metalloproteinase Inhibitors for Snakebite Envenoming in Brazil and Ghana

Acronym: TOCSINS

Important dates

Study start
2027
Primary completion
2028
Study completion
2028
First posted
Mar 30, 2026
Registry last updated
May 12, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.