Marcus V.G. LacerdaAlejandro Llanos-CuentasSrivicha KrudsoodChanthap LonDavid L. SaundersRezika MohammedDaniel YilmaDhelio Batista PereiraFe E.J. EspinoReginaldo Z. MiaRaul ChuquiyauriFernando ValMartín CasapíaWuelton M. MonteiroMarcelo A.M. BritoMônica R.F. CostaNillawan BuathongHarald NoedlErmias DiroSisay GetieKalehiwot M. WubieAlemseged AbdissaAhmed ZeynudinCherinet AbebeMauro S. TadaFrançoise BrandHans Peter BeckBrian AngusStephan DuparcJörg Peter KleimLynda M. KellamVictoria M. RousellSiôn W. JonesElizabeth HardakerKhadeeja MohamedDonna D. CloverKim FletcherJohn J. BretonCletus O. UgwuegbulamJustin A. GreenGavin C.K.W. KohGlaxoSmithKline, USAUniversity of GondarGokilaUniversidad Peruana Cayetano HerediaJimma UniversityUniversity of OxfordFundacao Oswaldo CruzUniversitat BaselMahidol UniversityMedizinische Universitat WienMedicines for Malaria VentureRio Tuba Nickel Foundation HospitalCentro de Pesquisas em Medicina Tropical2020-01-272020-01-272019-01-17New England Journal of Medicine. Vol.380, No.3 (2019), 215-22815334406002847932-s2.0-85060126699https://repository.li.mahidol.ac.th/handle/20.500.14594/51961Copyright © 2019 Massachusetts Medical Society. BACKGROUND Treatment of Plasmodium vivax malaria requires the clearing of asexual parasites, but relapse can be prevented only if dormant hypnozoites are cleared from the liver (a treatment termed “radical cure”). Tafenoquine is a single-dose 8-aminoquinoline that has recently been registered for the radical cure of P. vivax. METHODS This multicenter, double-blind, double-dummy, parallel group, randomized, placebo-controlled trial was conducted in Ethiopia, Peru, Brazil, Cambodia, Thailand, and the Philippines. We enrolled 522 patients with microscopically confirmed P. vivax infection (100 to 100,000 parasites per microliter) and normal glucose-6-phosphate dehydrogenase (G6PD) activity (with normal activity defined as ≥70% of the median value determined at each trial site among 36 healthy male volunteers who were otherwise not involved in the trial). All patients received a 3-day course of chloroquine (total dose of 1500 mg). In addition, patients were assigned to receive a single 300-mg dose of tafenoquine on day 1 or 2 (260 patients), placebo (133 patients), or a 15-mg dose of primaquine once daily for 14 days (129 patients). The primary outcome was the Kaplan-Meier estimated percentage of patients who were free from recurrence at 6 months, defined as P. vivax clearance without recurrent parasitemia. RESULTS In the intention-to-treat population, the percentage of patients who were free from recurrence at 6 months was 62.4% in the tafenoquine group (95% confidence interval [CI], 54.9 to 69.0), 27.7% in the placebo group (95% CI, 19.6 to 36.6), and 69.6% in the primaquine group (95% CI, 60.2 to 77.1). The hazard ratio for the risk of recurrence was 0.30 (95% CI, 0.22 to 0.40) with tafenoquine as compared with placebo (P0.001) and 0.26 (95% CI, 0.18 to 0.39) with primaquine as compared with placebo (P0.001). Tafenoquine was associated with asymptomatic declines in hemoglobin levels, which resolved without intervention. CONCLUSIONS Single-dose tafenoquine resulted in a significantly lower risk of P. vivax recurrence than placebo in patients with phenotypically normal G6PD activity.Mahidol UniversityMedicineArticleSCOPUS10.1056/NEJMoa1710775