Evaluating the efficacy and safety of therapeutic plasma exchange in snakebite-associated thrombotic microangiopathy compared to standard care alone: study protocol for a multicenter randomized controlled trial

Thrombotic microangiopathy (TMA) arising from Russell’s viper (RV) and hump-nosed pit viper (HNV) bites often leads to severe end-organ damage, including acute kidney injury (AKI). Therapeutic plasma exchange (TPE) is a resource-intense treatment, frequently employed in treating TMA, but its role as a management strategy remains unclear. Existing studies are small and observational in design only, and there is a lack of substantial empirical evidence for any efficacy of TPE. Clinical trials are required to assess the effectiveness of TPE in managing snakebite-induced TMA before it can be endorsed as standard care. This is a multicenter, open-label, randomized controlled trial aiming to assess the efficacy and safety of TPE in snakebite-associated TMA. Patients admitted or transferred within 5 days of an RV or HNV bite with evidence of TMA, with or without AKI, will be recruited. The interventional group will receive three cycles of TPE with fresh frozen plasma in addition to standard care. The control group will receive standard care alone. The trial aims to recruit a total of 60 subjects, with 30 allocated to each arm. Patients will be followed up at discharge and 3 months post-discharge. The primary outcome will be the composite measure of survival, dialysis dependency, or estimated glomerular filtration rate (eGFR) of <30 ml/min/1.73 m 2 at 3 months after discharge. Secondary outcomes include number of blood product transfusions, number and duration of dialysis received, duration of hospital stay, need for dialysis, survival to hospital discharge, eGFR < 30 ml/min/1.73 m 2 , and dialysis dependence at 3 months post-discharge. This trial has substantial clinical relevance as it evaluates the role of TPE as a treatment option in patients with snakebite-associated TMA, which has a high reported mortality and morbidity. Trial result would be useful in guiding the place of TPE with FFP in the management of TMA in snakebite, in the context of its high resource demand, and the existing uncertain evidence of its efficacy. Study findings will be disseminated through peer-reviewed publication. The trial has been registered in Sri Lanka Clinical Trial Registry (SLCTR/2024/008 on 15/03/2024) and Universal Trial Registry (UTN No: U1111-1297-0734).