A Phase 2 interventional study of lyophilized BPI viper antivenom in Daboia Siamensis Envenoming, sponsored by Myanmar Oxford Clinical Research Unit. Suspended at 1 site in Myanmar. Open to participants aged 16 Years and older. Per ClinicalTrials.gov, last updated 2024-04-01.
Sponsored by Myanmar Oxford Clinical Research Unit · Phase 2, Interventional, and Treatment
The aim of the study is to identify an 'optimal' initial dosing of the new Burma Pharmaceutical Industry (BPI) lyophilized mono-specific antivenom for patients with systemic Daboia siamensis envenoming. The initial dosing will aim to reverse venom-induced coagulopathy (as demonstrated by a negative 20 minutes Whole Blood Clotting Time (20WBCT) at 6 hours in 95% of patients whilst causing less than 5% anaphylactic reaction.
Snake-bite envenoming (SBE) was re-categorized as a priority neglected tropical disease by the World Health Organization (WHO) in 2017. Antivenom is considered to be one of the most cost effective health interventions. Despite this, due to challenges in manufacture, reliance on cold chain for transport and storage, and geographically remote location of most envenomed patients, many patients do not receive the antivenom they require in a timely manner. The WHO strategy for a globally coordinated response to SBE highlighted the need to prioritize clinical research into the safety and effectiveness of antivenoms.
Myanmar is a country with a high incidence of snake-bite with an estimated 25,000 snake-bites and 1250 deaths per year. Daboia siamensis (Eastern Russell's viper) is responsible for 85% of snake-bites presenting to hospitals in Myanmar. Given their natural habitat and abundance of prey within the paddy fields, envenoming predominantly occurs in rural areas affecting agricultural workers.
Following a recent 4-year collaborative initiative between institutions in Myanmar and Australia entitled the Myanmar Snakebite project, antivenom production facilities have improved resulting in the production of a new monospecific lyophilized F(ab)'2 antivenom (Viper antivenom BPI). The new lyophilized antivenom has replaced the former liquid antivenom and has been distributed countrywide. The current dosing strategy is based on unpublished results of pre-clinical testing and stratified into two doses according to absence or presence of clinical features of severity at presentation (80 mL and 160 mL, respectively). No clinical trial data or post marketing data has been published to support the efficacy or toxicity of these recommended doses. This lack of robust clinical evidence to support dosing of antivenom is mirrored across the world with few well conducted trials to determine the safety and efficacy of antivenoms.
This paper presents a novel phase 2, model based, Bayesian adaptive design to determine optimal antivenom dosing for Russell's viper envenoming. In this context there are two concurrent considerations for dose optimality. Firstly, the efficacy of the dose, defined in this context as restoration of blood coagulation within 6 hours; secondly, the dose-related toxicity, defined as the occurrence of an anaphylactic reaction within 180 minutes post antivenom administration. The model based design estimates dose-response curves for both the efficacy outcome and the toxicity outcome, and thus derives a user-defined 'optimal dose'. Patients will be randomized at a ratio of 4:1 to either adaptive dose or standard of care respectively.
The study team will perform a number of nested studies within the dose finding trial:
Myanmar Oxford Clinical Research Unit is the lead sponsor of 6 studies on the registry; none are open to participants now.
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Exclusion Criteria:
Patients will receive an initial antivenom dose of 80mL lyophilized BPI viper antivenom, as per current national guidelines
Biological: lyophilized BPI viper antivenom
Patients will receive an initial dose of lyophilized BPI viper antivenom determined by the adaptive model.
Biological: lyophilized BPI viper antivenom
Antivenom
Blood Coagulation
Blood coagulation at 6 hours as measured by the 20 minute WBCT (binary outcome)
Time frame: within 24 hours of patient recruitment
Anaphylaxis
Anaphylaxis as defined by the European Academy of Allergy and Immunology within 180 minutes of antivenom administration
Time frame: within 24 hours of patient recruitment
Time to restoration of blood coagulability as determined by the 20 WBCT.
Time frame: within 24 hours of patient recruitment
International normalized ratio (INR) determined by the POC INR meter.
Time frame: within 24 hours of patient recruitment
Blood coagulability as determined by PT and fibrinogen
Time frame: within 24 hours of patient recruitment
Occurrence of any serious adverse events
Time frame: within 24 hours of patient recruitment
The occurrence of envenoming sequelae at 3 month follow up
Time frame: within 6 months of patient recruitment
The occurrence of detectable ferryl-haem derivatives in urine samples
Time frame: within 6 months of patient recruitment
The occurrence of Capillary Leak Syndrome
Time frame: within 2 weeks of patient recruitment
Plan to share: Undecided — For ethics purposes, there is no current plans to share IPD with other researchers.
This study is suspended, as verified in Oct 2023. You cannot join it, but the record below documents what was studied.
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Myanmar Oxford Clinical Research Unit