Trial of Oral Community SVMP INhibitors for Snakebite

Официальное название

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

Обзор

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.

Вмешательства

• Препарат 2,3-dimercapto-1-propanesulfonic acid
  Oral administration
• Препарат marimastat
  oral administration
• Препарат Oral placebo capsules
  Oral placebo
• Препарат Antivenom Snakes
  Standard of care IV antivenom recommended in country

Первичные конечные точки

• Mean time until lab INR is less than 50% of the baseline value (efficacy) [Срок оценки: From randomisation until end of admission]
• Incidence (cumulative) of safety events (safety) [Срок оценки: From informed consent until 42 days after randomisation]

Вторичные конечные точки (12)

• Stage A- Assess the effect of pre-hospital treatment on INR improvement based on travel time to hospital. [Срок оценки: Day 0 clinic and hospital]
• Stage A- Assess the effect of pre-hospital treatment on fibrinogen improvement based on travel time to hospital. [Срок оценки: Day 0 clinic and hospital]
• Stage A and B- To determine the acceptability of the intervention between treatment arms in terms of quality of life. [Срок оценки: Day 14, Day 42 (Stage A and B)]
• Stage A and B- To determine the acceptability of the intervention between treatment arms as patient-reported outcomes of functioning. [Срок оценки: Day 14 and Day 42 post-randomisation (Stage A and B)]
• Stage A and B- To evaluate the reach of the intervention (Participant refusal rate) [Срок оценки: Day 0 clinic (Stage A) or hospital (Stage B)]
• Stage A and B- To evaluate the reach of the intervention (Exclusion rate) [Срок оценки: Day 0 clinic (Stage A) or hospital (Stage B)]
• Stage A and B- To evaluate the reach of the intervention (Time between bite and treatment received) [Срок оценки: Day 0 clinic (Stage A) or hospital (Stage B)]
• Stage A and B-To evaluate the reach of the intervention based on recruitment rate across the study catchment area (Recruitment rate) [Срок оценки: Day 0 clinic (Stage A) or hospital (Stage B)]
• Stage A and B- Identify benefits of and barriers for future implementation of the intervention. [Срок оценки: Day 42]
• Stage A- To determine differences in resolution of clinically relevant non-serious bleeding events. [Срок оценки: Day 0 clinic and hospital]
• Stage B- Assess the effect of time to treatment on INR improvement (based on estimated time from bite until administration of the treatment). [Срок оценки: 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). [Срок оценки: Day 0 hospital]

Критерии участия

Критерии включения

• 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)

Критерии исключения

• 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)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07500233 · 25-033-310

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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