tetano
Editor, Senior Moderator
Br J Clin Pharmacol
. 2021 Jul 30.
doi: 10.1111/bcp.15013. Online ahead of print.
Effect of hydroxychloroquine on the cardiac ventricular repolarization - a randomized clinical trial
Boukje C Eveleens Maarse[SUP] 1 [/SUP], Claus Graff[SUP] 2 [/SUP], Jørgen K Kanters[SUP] 3 [/SUP], Michiel J van Esdonk[SUP] 1 [/SUP], Michiel J B Kemme[SUP] 4 [/SUP], Aliede E In't Veld[SUP] 1 5 [/SUP], Manon A A Jansen[SUP] 1 [/SUP], Matthijs Moerland[SUP] 1 5 [/SUP], Pim Gal[SUP] 1 5 [/SUP]
Affiliations
Abstract
Introduction: Hydroxychloroquine has been suggested as possible treatment for Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2). Studies reported an increased risk of QTcF-prolongation after treatment with hydroxychloroquine. The aim of this study was to analyze the concentration-dependent effects of hydroxychloroquine on the ventricular repolarization, including QTcF-duration and T-wave morphology.
Methods: Twenty young (≤30 years) and twenty elderly (65 - 75 years) 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. ECGs were recorded as triplicate at baseline and four post-dose 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 (MCS), were analyzed with a pre-specified 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 = 0.09, 0.34, 0.25). 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 (200ng/mL). There were no associations between hydroxychloroquine concentration and the T-wave morphology (p = 0.34 for MCS). 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.
Keywords: QT-interval; cardiac ventricular repolarization; concentration-effect analysis; electrocardiogram; hydroxychloroquine.
. 2021 Jul 30.
doi: 10.1111/bcp.15013. Online ahead of print.
Effect of hydroxychloroquine on the cardiac ventricular repolarization - a randomized clinical trial
Boukje C Eveleens Maarse[SUP] 1 [/SUP], Claus Graff[SUP] 2 [/SUP], Jørgen K Kanters[SUP] 3 [/SUP], Michiel J van Esdonk[SUP] 1 [/SUP], Michiel J B Kemme[SUP] 4 [/SUP], Aliede E In't Veld[SUP] 1 5 [/SUP], Manon A A Jansen[SUP] 1 [/SUP], Matthijs Moerland[SUP] 1 5 [/SUP], Pim Gal[SUP] 1 5 [/SUP]
Affiliations
- PMID: 34327732
- DOI: 10.1111/bcp.15013
Abstract
Introduction: Hydroxychloroquine has been suggested as possible treatment for Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2). Studies reported an increased risk of QTcF-prolongation after treatment with hydroxychloroquine. The aim of this study was to analyze the concentration-dependent effects of hydroxychloroquine on the ventricular repolarization, including QTcF-duration and T-wave morphology.
Methods: Twenty young (≤30 years) and twenty elderly (65 - 75 years) 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. ECGs were recorded as triplicate at baseline and four post-dose 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 (MCS), were analyzed with a pre-specified 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 = 0.09, 0.34, 0.25). 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 (200ng/mL). There were no associations between hydroxychloroquine concentration and the T-wave morphology (p = 0.34 for MCS). 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.
Keywords: QT-interval; cardiac ventricular repolarization; concentration-effect analysis; electrocardiogram; hydroxychloroquine.