Safety and Efficacy of 3 Alternative Regimens Against Relapsing Plasmodium vivax Malaria in Glucose 6-Phosphate Dehydrogenase-Deficient Patients in the Brazilian Amazon (ALTPRIM).

Abstract

Daily primaquine-induced hemolysis is a common cause of complications during Plasmodium vivax malaria treatment in individuals with glucose 6-phosphate dehydrogenase deficiency (G6PDd). Alternative regimens balancing safety and efficacy are needed. G6PDd participants with P. vivax malaria from 2 sites in Brazilian Amazon between 2018 and 2022 were randomly allocated to 3 arms that received chloroquine (CQ) from day 1 to day 3 plus (arm 1) a 7-day course of primaquine (PQ) (0.5 mg/kg/day), beginning at day 5; (arm 2) weekly PQ over 8 weeks (0.75 mg/kg/wk); or (arm 3) weekly CQ over 12 weeks (5 mg/kg/wk). A normal-G6PD participants group was also enrolled in parallel using CQ for 3 days plus PQ for 7 days. The primary focus was safety profile; secondary was the number of patients free from the first recurrence until day 180. Fifty-four G6PDd participants were enrolled. There were 2 participants in arm 1, but the arm was halted due to safety concerns. The weekly PQ group presented higher hemoglobin decreases in day 3 after first dose (Δhemoglobin = -1.61) than the weekly CQ group (Δhemoglobin = -0.99), but efficacy was superior over the 6-month follow-up. Postponing the beginning of daily PQ to day 5, when less oxidative stress related to malaria itself would, in theory, decrease hemolytic effects of the drug in G6PDd patients, was not shown to be safe. Weekly CQ avoiding the first relapse did not stop further relapses. Weekly PQ, as already demonstrated in Southeast Asia, was equally safe and efficacious in patients from Latin America. Clinical Trials Registration. NCT03529396.