Tafenoquine plus chloroquine for the treatment and relapse prevention of Plasmodium vivax malaria (DETECTIVE): a multicentre, double-blind, randomised, phase 2b dose-selection study

BACKGROUND: Clinical effectiveness of previous regimens to treat Plasmodium vivax infection have been hampered by compliance. We aimed to assess the dose-response, safety, and tolerability of single-dose tafenoquine plus 3-day chloroquine for P vivax malaria radical cure. METHODS: In this double-blind, randomised, dose-ranging phase 2b study, men and women (aged >/=16 years) with microscopically confirmed P vivax monoinfection (parasite density >100 to 7500 per muL blood). The primary efficacy endpoint was relapse-free efficacy at 6 months from initial dose (ie, clearance of initial infection without subsequent microscopically confirmed infection), analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01376167. FINDINGS: Between Sept 19, 2011, and March 25, 2013, 329 patients were randomly assigned to a treatment group (chloroquine plus tafenoquine 50 mg [n=55], 100 mg [n=57], 300 mg [n=57], 600 mg [n=56]; or to chloroquine plus primaquine [n=50]; or chloroquine alone [n=54]). Relapse-free efficacy at 6 months was 57.7% (95% CI 43-70) with tafenoquine 50 mg, 54.1% (40-66) with tafenoquine 100 mg, 89.2% (77-95) with tafenoquine 300 mg, 91.9% (80-97) with tafenoquine 600 mg, 77.3% (63-87) with primaquine, and 37.5% (23-52) with chloroquine alone. Tafenoquine 300 mg and 600 mg had better efficacy than chloroquine alone (treatment differences 51.7% [95% CI 35-69], p