Effect of Hydroxychloroquine, azithromycin and Lopinavir/ritonavir on the QT corrected interval in patients with COVID-19: Effect of triple therapy on QTc in patients with COVID-19.

Echarte-Morales, Julio; Minguito-Carazo, Carlos; del Castillo García, Samuel; Borrego-Rodríguez, Javier; Rodríguez-Santamarta, Miguel; Sánchez-Muñoz, Enrique; García, Rubén Bergel; Maniega, Clea González; Prieto-González, Silvia; Suarez, Paula Menéndez; Tundidor-Sanz, Elena; Benito-González, Tomás; Fernández-Vázquez, Felipe

Background: Administration of Hydroxychloroquine and Azithromycin in patients with coronavirus disease 2019 (COVID-19) prolongs QTc corrected interval (QTc). The effect and safety of Lopinavir/Ritonavir in combination with these therapies have seldom been studied. Objectives: Our aim was to evaluate changes in QTc in patients receiving double (Hydroxychloroquine + Azithromycin) and triple therapy (Hydroxychloroquine + Azithromycin + Lopinavir/Ritonavir) to treat COVID-19. Secondary outcome was the incidence of in-hospital all-cause mortality. Methods: Patients under treatment with double (DT) and triple therapy (TT) for COVID-19 were consecutively included in this prospective observational study. Serial in-hospital electrocardiograms were performed to measure QTc at baseline and during therapy. Results: 168 patients (±66.2 years old) were included: 32.1% received DT and 67.9% received TT. The mean baseline QTc was 410.33 ms. Patients under DT and TT prolonged QTc interval respect baseline values (p < 0.001), without significant differences between both therapy groups (p = 0.748). Overall, 33 patients (19.6%) had a peak QTc and/or an increase QTc 60 ms from baseline, with a higher prevalence among those with hypokalemia (p = 0.003). All-cause mortality was similar between both strategy groups (p = 0.093) and high risk QTc prolongation was no related to clinical events in this series. Conclusions: DT and TT prolong the QTc in patients with COVID-19. Addition of Lopinavir/Ritonavir on top of Hydroxychloroquine and Azithromycin did not increase QTc compared to DT.