The DETECTIVE trial: tafenoquine reduces risk of Plasmodium vivax relapse

1. After initial chloroquine treatment, P. vivax malaria infected patients treated with tafenoquine had significantly lower rates of P. vivax infection at 6 months compared to patients given placebo.

2. Mean hemoglobin levels were mildly reduced in the tafenoquine group but returned to baseline after treatment.

Evidence Rating Level: 1 (Excellent)      

Study Rundown: P. vivax, one of the causative pathogens of malaria, can infect a substantial portion of the world population and be difficult to completely treat due to different life stages of the parasite. Generally, chloroquine is used to treat asexual parasites and a subsequent 14-day treatment with a primaquine clears hypnozoites. Due to adherence difficulties, a shorter course of treatment for hypnozoites is sought. This study evaluated clearance of P. vivax infection in patients treated with chloroquine followed by a single dose of the long acting drug tafenoquine, placebo, or a 14-day regimen of primaquine. After 6 months, patients treated with tafenoquine had a significantly lower relapse for infection rate than those treated with placebo, and had a comparable relapse rate as those in the primaquine group. Hemoglobin levels were mildly lower for a brief period after tafenoquine treatment but returned to baseline in all patients.

This study supports use of a single dose treatment for clearance of hypnozoites in P. vivax malaria infected patients. Though the study is limited in the number of patients included and subsequent hazard ratios for various outcomes were often large, results were conclusive across all subgroups assessed that tafenoquine is substantially more effective than placebo after chloroquine treatment.

Click to read the study in NEJM

Relevant Reading: Tafenoquine: a promising new antimalarial agent

In-Depth [randomized controlled trial]: This international, double-blind, parallel-group, randomized controlled trial enrolled patients from 2014 to 2016. Patients had microscopically confirmed P. vivax infection and had normal levels of glucose-6-phosphate dehydrogenase (G6PD) activity, as tafenoquine can cause hemolysis in those with low G6PD levels. All patients were given 3 days of chloroquine and then randomized in a 2:1:1 fashion to receive a single dose of tafenoquine (n=260), primaquine (n=129), or placebo (n=133). Patients were followed up until 180 days after treatment to assess for clinical and hematologic evidence of relapsed P. vivax infection. The primary outcome of recurrence-free efficacy, or having no evidence of P. vivax infection, was found in 62.4%, 69.6%, and 27.7% of the tafenoquine, primaquine, and placebo groups, respectively. The hazard ratio for risk of recurrence was 0.30 (95% CI, 0.22 to 0.40; P<0.001) for tafenoquine compared to placebo and 0.26 (95% CI, 0.18 to 0.39; P<0.001) for primaquine compared to placebo. After 3 days (or the completion of the chloroquine regimen) parasite clearance occurred in over 80% of patients in all groups. Overall rates of adverse effects were similar between patients in all groups, with dizziness and decreased hemoglobin levels the most common occurrences. Declines in hemoglobin of 30% of more from baseline occurred in 5.4%, 1.6%, and 1.5% of patients in the tafenoquine, primaquine, and placebo groups, respectively. Return to baseline hemoglobin levels generally occurred by day 30 of the study.

Image: PD

©2019 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc