Publication: Randomized controlled trial of the electrocardiographic effects of four antimalarials for pregnant women with uncomplicated Malaria on the Thailand-Myanmar border
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Issued Date
2021-04-01
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ISSN
10986596
00664804
00664804
Other identifier(s)
2-s2.0-85103059090
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Mahidol University
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SCOPUS
Bibliographic Citation
Antimicrobial Agents and Chemotherapy. Vol.65, No.4 (2021)
Suggested Citation
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 Randomized controlled trial of the electrocardiographic effects of four antimalarials for pregnant women with uncomplicated Malaria on the Thailand-Myanmar border. Antimicrobial Agents and Chemotherapy. Vol.65, No.4 (2021). doi:10.1128/AAC.02473-20 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/78311
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Title
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 (AL1). 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 AL1, 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 AL1 group, but not different in the ASMQ group (2.45 ms; 95% CI, 24.20 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.