Randomized Controlled Trial of the Electrocardiographic Effects of Four Antimalarials for Pregnant Women with Uncomplicated Malaria on the Thailand-Myanmar Border.
|
| Abstract |
Quinoline antimalarials cause drug-induced electrocardiographic QT prolongation, a potential risk factor for torsade de pointes. The effects of currently used antimalarials on the electrocardiogram (ECG) were assessed in pregnant women with malaria. Pregnant women with microscopy-confirmed parasitemia of any malaria species were enrolled in an open-label randomized controlled trial on the Thailand-Myanmar border from 2010 to 2016. Patients were randomized to the standard regimen of dihydroartemisinin-piperaquine (DP) or artesunate-mefloquine (ASMQ) or an extended regimen of artemether-lumefantrine (AL+). Recurrent Plasmodium vivax infections were treated with chloroquine. Standard 12-lead electrocardiograms were assessed on day 0, 4 to 6 h following the last dose, and day 7. QT was corrected for the heart rate by a linear mixed-effects model-derived population-based correction formula (QTcP = QT/RR0.381). A total of 86 AL+, 82 ASMQ, 88 DP, and 21 chloroquine-treated episodes were included. No patients had an uncorrected QT interval nor QTcP of >480 ms at any time. QTcP corresponding to peak drug concentration was longer in the DP group (adjusted predicted mean difference, 17.84 ms; 95% confidence interval [CI], 11.58 to 24.10; P < 0.001) and chloroquine group (18.31 ms; 95% CI, 8.78 to 27.84; P < 0.001) than in the AL+ group, but not different in the ASMQ group (2.45 ms; 95% CI, -4.20 to 9.10; P = 0.47) by the multivariable linear mixed-effects model. There was no difference between DP and chloroquine (P = 0.91). QTc prolongation resulted mainly from widening of the JT interval. In pregnant women, none of the antimalarial drug treatments exceeded conventional thresholds for an increased risk of torsade de pointes.
|
|---|---|
| Authors | Makoto Saito, Widi Yotyingaphiram, Zillah Cargill, Mary Ellen Gilder, Aung Myat Min, Aung Pyae Phyo, Thi Dar San, Hilda Poe, Cindy Chu, Nicholas J White, François Nosten, Rose McGready |
| Journal | Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 65 Issue 4 (03 18 2021) ISSN: 1098-6596 [Electronic] United States |
| PMID | 33495217 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2021 Saito et al. |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!