Tafenoquine co-administered with dihydroartemisinin-piperaquine for the radical cure of Plasmodium vivax malaria (INSPECTOR): a randomised, placebo-controlled, efficacy and safety study

Sutanto, I; Soebandrio, A; Ekawati, LL; Chand, K; Noviyanti, R; Satyagraha, AW; Subekti, D; Santy, YW; Crenna-Darusallam, C; Instiaty, I; Budiman, W; Prasetya, CB; Lardo, S; Elyazar, I; Duparc, S; Cedar, E; Rolfe, K; Fernando, D; Berni, A; Jones, S; Kleim, J-P; Fletcher, K; Sharma, H; Martin, A; Taylor, M; Goyal, N; Green, JA; Tan, LK; Baird, JK

Journal article

Tafenoquine co-administered with dihydroartemisinin-piperaquine for the radical cure of Plasmodium vivax malaria (INSPECTOR): a randomised, placebo-controlled, efficacy and safety study

Abstract:: 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.

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Sutanto, I., Soebandrio, A., Ekawati, L. L., Chand, K., Noviyanti, R., Satyagraha, A. W., Subekti, D., Santy, Y. W., Crenna-Darusallam, C., Instiaty, I., Budiman, W., Prasetya, C. B., Lardo, S., Elyazar, I., Duparc, S., Cedar, E., Rolfe, K., Fernando, D., Berni, A., … Baird, J. K. (2023). Tafenoquine co-administered with dihydroartemisinin-piperaquine for the radical cure of Plasmodium vivax malaria (INSPECTOR): a randomised, placebo-controlled, efficacy and safety study. Lancet Infectious Diseases, 23(10), 1153–1163.

MLA Style

Sutanto, I., et al. “Tafenoquine Co-Administered with Dihydroartemisinin-Piperaquine for the Radical Cure of Plasmodium Vivax Malaria (INSPECTOR): a Randomised, Placebo-Controlled, Efficacy and Safety Study.” Lancet Infectious Diseases, vol. 23, no. 10, Elsevier, 2023, pp. 1153–63.

Chicago Style

Sutanto, I, A Soebandrio, LL Ekawati, K Chand, R Noviyanti, AW Satyagraha, D Subekti, et al. 2023. “Tafenoquine Co-Administered with Dihydroartemisinin-Piperaquine for the Radical Cure of Plasmodium Vivax Malaria (INSPECTOR): a Randomised, Placebo-Controlled, Efficacy and Safety Study.” Lancet Infectious Diseases 23 (10): 1153–63.
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