Snakebite Injury, Occupational Diseases, Poisoning
Conditions
Interventions
Randomisation and dosing:
Randomisation will use a novel Personalised Randomised Controlled Trial (PRACTical) design, in which each participant is randomised only to pre-defined antivenoms that are a
however, repeat administration of the same antivenom at the same dose may be considered at 8h after randomisation (typically ~6-7h after the first administration) if a participant presenting with coag
Sponsors
Liverpool School of Tropical Medicine
Eligibility
Sex/Gender
All
Age
2 Years to 100 Years
Inclusion criteria
Inclusion criteria: 1. =2 years of age 2. Presenting to the hospital reporting having been bitten by a snake and with evidence of systemic envenoming, defined as any of the following: 2.1. Coagulopathy, defined as no evidence of clotting on a 20-minute whole blood clotting test (20WBCT) (performed as part of standard clinical practice) 2.2. Shock defined by systolic blood pressure (see below) persisting 30 mins after a weight-dependent fluid bolus. A single post-bolus blood pressure reading will be used to determine eligibility. 2.2.1. 2-5 years of age 13 years <90 mmHg 2.3. Neurotoxicity, defined as one or more of the following symptoms: bilateral ptosis, ophthalmoplegia, airway compromise or ventilatory failure presenting within 24 hours of a bite 3. Not received antivenom for this snakebite, at the presenting hospital or any other healthcare facility (including a local health centre) 4. Participant or proxy or parent/guardian willing and able to provide consent (written or, depending on severity of presentation, verbal consent confirmed by written consent as soon as possible). Verbal consent allows for the administration of antivenom at no or minimal delay.
Exclusion criteria
Exclusion criteria: 1. If presenting with coagulopathy: currently known to be receiving anti-coagulant therapy including warfarin, heparin or heparin derivatives or direct oral anticoagulants (DOAC) 2. Active (current) participation in another trial of antivenom or small molecule treatments for envenoming 3. Previous participation in this trial with a reaction to trial antivenom
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| In participants with signs of systemic envenoming at presentation, specifically coagulopathy or shock, the primary endpoint, reflecting “success”, will be defined by the participant being alive and having: 1. Resolution of shock at 3h from randomisation in participants with evidence of shock at baseline (defined by age-specific systolic blood pressure) (note: all participants presenting with shock must receive weight-dependent fluid boluses, so primary endpoint reflects resolution with antivenom and fluid bolus) 2. International normalised ratio (INR) 1.4 (diagnostic criteria based on external evidence) but no evidence of shock) In participants with only neurotoxicity at presentation (exploratory outcome): The primary endpoint, reflecting “success”, will be defined by the participant having no requirement for mechanical or manual ventilation within 48h from randomisation | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy will be measured in all participants using: 1. All-cause mortality through 42 days from randomisation 2. WHO 12-item disability assessment scale 2.0 (WHO-DAS) at 42 days from randomisation (5 years and older) or Washington Child Functioning Module (aged 2-4 years) 3. Patient-specific functional scale (PSFS) at 14 and 42 days from randomisation Efficacy (any evidence of coagulopathy): • INR 0.5 g/L at 8h and 14h from randomisation • Mean change in fibrinogen from baseline to 8h and 14h from randomisation • Cessation of bleeding at 8h from randomisation (in those with evidence of active bleeding at randomisation) • Development of new major or clinically relevant non-major bleeding 8-48h from randomisation (major bleeding as defined by International Society on Thrombosis and Haemostasis (ISTH) criteria) • Development of new major bleeding from 8 hours through 7 days from randomisation Efficacy (neurotoxicity only): • Requirement for intubation within 48h from randomisation • Duration of any mechanical or manual ventilation given through 42 days from randomisation Safety (all) • Severe (Grade 3/4 following the Brown grading) allergic reactions (hypotension, hypoxia, or neurological compromise) within 6h of first administration following randomisation • Severe (Grade 3/4) allergic reactions (hypotension, hypoxia, or neurological compromise) within 6h of any administration following randomisation (Brown grading) • Allergic reactions (any grade) within 6h of first administration following randomisation (Brown grading) • Allergic reactions (any grade) within 6h of any administration following randomisation (Brown grading) • Serum sickness through 14 and 42 days from randomisation (defined by the Australian Snakebite Project (ASP)) | — |
Countries
Ghana, Togo
Contacts
Public ContactKristen LeBeau
Outcome results
None listed