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Effect of hydroxychloroquine on the cardiac ventricular repolarization: A randomized clinical trial
Author(s) -
Eveleens Maarse Boukje C.,
Graff Claus,
Kanters Jørgen K.,
Esdonk Michiel J.,
Kemme Michiel J. B.,
Veld Aliede E.,
Jansen Ma A. A.,
Moerland Matthijs,
Gal Pim
Publication year - 2022
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.15013
Subject(s) - hydroxychloroquine , medicine , qt interval , qrs complex , cardiology , placebo , confidence interval , repolarization , pr interval , anesthesia , heart rate , covid-19 , blood pressure , electrophysiology , alternative medicine , disease , pathology , infectious disease (medical specialty)
Aims Hydroxychloroquine has been suggested as possible treatment for severe acute respiratory syndrome‐coronavirus‐2. Studies reported an increased risk of QTcF‐prolongation after treatment with hydroxychloroquine. The aim of this study was to analyse the concentration‐dependent effects of hydroxychloroquine on the ventricular repolarization, including QTcF‐duration and T‐wave morphology. Methods Twenty young (≤30 y) and 20 elderly (65–75 y) healthy male subjects were included. Subjects were randomized to receive either a total dose of 2400 mg hydroxychloroquine over 5 days, or placebo (ratio 1:1). Follow‐up duration was 28 days. Electrocardiograms (ECGs) were recorded as triplicate at baseline and 4 postdose single recordings, followed by hydroxychloroquine concentration measurements. ECG intervals (RR, QRS, PR, QTcF, J‐Tpc, Tp‐Te) and T‐wave morphology, measured with the morphology combination score, were analysed with a prespecified linear mixed effects concentration–effect model. Results There were no significant associations between hydroxychloroquine concentrations and ECG characteristics, including RR‐, QRS‐ and QTcF‐interval ( P = .09, .34, .25). Mean ΔΔQTcF‐interval prolongation did not exceed 5 ms and the upper limit of the 90% confidence interval did not exceed 10 ms at the highest measured concentrations (200 ng/mL). There were no associations between hydroxychloroquine concentration and the T‐wave morphology ( P = .34 for morphology combination score). There was no significant effect of age group on ECG characteristics. Conclusion In this study, hydroxychloroquine did not affect ventricular repolarization, including the QTcF‐interval and T‐wave morphology, at plasma concentrations up to 200 ng/mL. Based on this analysis, hydroxychloroquine does not appear to increase the risk of QTcF‐induced arrhythmias.