Efficacy of Dual Parenteral Artemisinin-Based Combination Therapy for Cerebral Malaria in a Tripple Blinded Randomized Control Trial in Nigerian Children: DUAL PACT TRIAL

Abstract Background : Evidence exists as to the criticality of the first 24 hours in the management of cerebral malaria. This could serve as a potential safety net for improved outcomes with prompt treatment and utilization of effective therapy. The morbidity and the mortality rate (35%) with the current parenteral monotherapy for the initial treatment of cerebral malaria is unacceptably high. Combination therapy and a shorter course of effective medication have been shown to improve outcomes in human subjects in treatment of other diseases. This study outlines a protocol to conduct a triple blinded randomized control trial on cerebral malaria using dual parenteral medications compared to the current standard of monotherapy. Methods : This is a randomized control triple blinded trial consisting of an intervention and 2 control arms. Eligible and assenting children aged 6 months to 17 years will be recruited from 4 tertiary hospitals by random selection from the list of tertiary hospitals in Nigeria. Subjects will be concealed and allocated in parallel into three arms using random numbers generated from GraphPad Prism (version 9) by a Clinical Pharmacologist who has no link with the investigators, the patients, or the statistician. The parasite load and clearance, fever defervesence, C reactive protein, procalcitonin, blood glucose, electrocardiograms and time to regain consciousness will be monitored. The socio-demographic and clinical details of all patients will be documented. The study will be conducted in line with Declaration of Hesinki 2013. Appropriate statistical tools will be used for data collection and analysis. Discussion :The outcome of this analysis will give insight into the efficacy of dual parenteral antimalaria in the treatment of cerebral malaria among Nigerian children compared with standard of care. The safety profile of this intervention would also be highlighted. This may help inform Physicians on the optimal treatment for cerebral malaria to improve outcomes, prevent development of resistance, recrudescence, treatment failure and stimulate interest of pharmaceutical companies in the development of newer formulations of dual parenteral antimalarial combination therapies. Trial registration : This study was registered in the Pan Africa Clinical Trial Registry (PACTR202102893629864).