Effect of hydroxychloroquine on the cardiac ventricular repolarization: A randomized clinical trial
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Effect of hydroxychloroquine on the cardiac ventricular repolarization : A randomized clinical trial. / Eveleens Maarse, Boukje C.; Graff, Claus; Kanters, Jørgen K.; van Esdonk, Michiel J.; Kemme, Michiel J.B.; in 't Veld, Aliede E.; Jansen, Manon A.A.; Moerland, Matthijs; Gal, Pim.
In: British Journal of Clinical Pharmacology, Vol. 88, No. 3, 03.2022, p. 1054-1062.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Effect of hydroxychloroquine on the cardiac ventricular repolarization
T2 - A randomized clinical trial
AU - Eveleens Maarse, Boukje C.
AU - Graff, Claus
AU - Kanters, Jørgen K.
AU - van Esdonk, Michiel J.
AU - Kemme, Michiel J.B.
AU - in 't Veld, Aliede E.
AU - Jansen, Manon A.A.
AU - Moerland, Matthijs
AU - Gal, Pim
N1 - Funding Information: The study was funded by the Centre for Human Drug Research, Leiden, The Netherlands. Publisher Copyright: © 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
PY - 2022/3
Y1 - 2022/3
N2 - 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.
AB - 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.
KW - cardiac ventricular repolarization
KW - concentration–effect analysis
KW - electrocardiogram
KW - hydroxychloroquine
KW - QT-interval
U2 - 10.1111/bcp.15013
DO - 10.1111/bcp.15013
M3 - Journal article
C2 - 34327732
AN - SCOPUS:85113718166
VL - 88
SP - 1054
EP - 1062
JO - British Journal of Clinical Pharmacology, Supplement
JF - British Journal of Clinical Pharmacology, Supplement
SN - 0264-3774
IS - 3
ER -
ID: 306683725