Tafenoquine co-administered with dihydroartemisinin–piperaquine for the radical cure of Plasmodium vivax malaria (INSPECTOR): a randomised, placebo-controlled, efficacy and safety study - 28/09/23
Summary |
Background |
Tafenoquine, co-administered with chloroquine, is approved for the radical cure (prevention of relapse) of Plasmodium vivax malaria. In areas of chloroquine resistance, artemisinin-based combination therapies are used to treat malaria. This study aimed to evaluate tafenoquine plus the artemisinin-based combination therapy dihydroartemisinin–piperaquine for the radical cure of P vivax malaria.
Methods |
In this double-blind, double-dummy, parallel group study, glucose-6-phosphate dehydrogenase-normal Indonesian soldiers with microscopically confirmed P vivax malaria were randomly assigned by means of a computer-generated randomisation schedule (1:1:1) to dihydroartemisinin–piperaquine alone, dihydroartemisinin–piperaquine plus a masked single 300-mg dose of tafenoquine, or dihydroartemisinin–piperaquine plus 14 days of primaquine (15 mg). The primary endpoint was 6-month relapse-free efficacy following tafenoquine plus dihydroartemisinin–piperaquine versus dihydroartemisinin-piperaquine alone in all randomly assigned patients who received at least one dose of masked treatment and had microscopically confirmed P vivax at baseline (microbiological intention-to-treat population). Safety was a secondary outcome and the safety population comprised all patients who received at least one dose of masked medication. This study is registered with ClinicalTrials.gov, NCT02802501 and is completed.
Findings |
Between April 8, 2018, and Feb 4, 2019, of 164 patients screened for eligibility, 150 were randomly assigned (50 per treatment group). 6-month Kaplan-Meier relapse-free efficacy (microbiological intention to treat) was 11% (95% CI 4–22) in patients treated with dihydroartemisinin–piperaquine alone versus 21% (11–34) in patients treated with tafenoquine plus dihydroartemisinin–piperaquine (hazard ratio 0·44; 95% CI [0·29–0·69]) and 52% (37–65) in the primaquine plus dihydroartemisinin-piperaquine group. Adverse events over the first 28 days were reported in 27 (54%) of 50 patients treated with dihydroartemisinin–piperaquine alone, 29 (58%) of 50 patients treated with tafenoquine plus dihydroartemisinin–piperaquine, and 22 (44%) of 50 patients treated with primaquine plus dihydroartemisinin–piperaquine. Serious adverse events were reported in one (2%) of 50, two (4%) of 50, and two (4%) of 50 of patients, respectively.
Interpretation |
Although tafenoquine plus dihydroartemisinin–piperaquine was statistically superior to dihydroartemisinin–piperaquine alone for the radical cure of P vivax malaria, the benefit was not clinically meaningful. This contrasts with previous studies in which tafenoquine plus chloroquine was clinically superior to chloroquine alone for radical cure of P vivax malaria.
Funding |
ExxonMobil, Bill & Melinda Gates Foundation, Newcrest Mining, UK Government all through Medicines for Malaria Venture; and GSK.
Translation |
For the Indonesian translation of the abstract see Supplementary Materials section.
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Vol 23 - N° 10
P. 1153-1163 - octobre 2023 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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