Study design and participants
infection
INFECTION, SECONDARY
This double-blind, double-dummy, randomised, parallel group study enrolled soldiers from two battalions based in East Java (battalion 1 at Malang; battalion 2 at Madiun; Patients were eligible for enrolment if they were male, aged at least 18 years, had microscopically confirmed The main exclusion criteria were severe The trial was designed to support the use of tafenoquine 300 mg with dihydroartemisinin–piperaquine. The underlying relapse rate following a course of dihydroartemisinin–piperaquine cannot be assumed from historical data owing to the natural variation in both infection rates and relapse rates among infected subjects. The dihydroartemisinin–piperaquine alone group was included as a relapse-prevention placebo control to provide an efficacy benchmark in the same setting and at the same time as the study treatment groups. The inclusion of the primaquine group provided a context against which to interpret the observed tafenoquine efficacy rate. A statistical comparison for non-inferiority between tafenoquine and primaquine was not done; such a comparison would require a considerably larger sample size and was not the main objective of the study, which was to estimate the efficacy of tafenoquine.The study complied with Good Clinical Practice, the Declaration of Helsinki, and relevant regulatory requirements. Ethics approval was obtained from the Oxford Tropical Research Ethics Committee (Project 9-16) and the Faculty of Medicine Universitas Indonesia Ethics Committee (FKUI 593/UNs.F1/ETIK/2016 dated July 18, 2016). Written informed consent was obtained individually from study patients and affirmed by an independent peer witness. Army rank superiors were not permitted to witness or participate in the consenting process to avoid any perception of coercion. The protocol was amended once on April 20, 2017 (before study start) to include an additional secondary objective requested by the Indonesian regulatory agency: comparison of dihydroartemisinin–piperaquine plus primaquine (as per national treatment guidelines) with dihydroartemisinin–piperaquine alone. The full protocol is available online (NCT 02802501).