QT interval monitoring for inpatient treated with hydroxychloroquine/azithromycin association in the context of SARS-CoV-2 pandemic

Background There are ongoing clinical trials on the efficacy of several therapeutic strategies for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Among them, the association between hydroxychloroquine (HCQ) and azithromycin (AZT) is under evaluation. Both drugs have a known torsadogenic potential, but QT prolongation induced by this association for inpatient is unknown. Objective To assess QT monitoring of inpatient treated with the association HCQ/AZT for SARS-CoV-2. Methods Before therapy initiation, a baseline 12 lead-ECG was electronically sent to our cardiology department for QT analysis (automatic measurement, and Bazett/Fridericia calculation with manual measurement), and after two days of treatment. An institutional protocol (Pasteur University Hospital, Nice) was validated, and allowed HCQ/AZT initiation only if baseline QTc ≥ 480ms and potassium level > 4.0 mmol/L. Results From March 24th to April 19th, 71 patients were included (mean age 62 ± 14 years, male 66%). Three patients out of 71 (4.2%) were not eligible for drug initiation (QTc ≥ 500ms), and the treatment had to be stopped because of significant QTc prolongation in 2 out of 68 patients (2.9%): concurrent QT-prolonging medication polypharmacy in both patients. Baseline mean QTc was 418 ± 30 ms and lengthened to 442 ± 46 ms after 48 hours of combined therapy ( Fig. 1 ). The agreement coefficient between automatic measurement of QT interval and manual measurements (variability below 5%) was calculated at 57%. Conclusion A combined therapy, using HCQ/AZT for inpatient SARS-CoV-2, required a close ECG monitoring. This association had to be interrupted in 2.9% of the patients treated.