Combined use of hydroxychloroquine and azithromycin was globally
adopted, in part due to paucity and high cost of alternative therapies.
However the utility of these medications has been questioned; and thus
safety becomes a major concern given clinical equipoise regarding
efficacy. Both hydroxychloroquine and azithromycin continue to be
administered in US clinical trials examining their potential role in
prevention of infection, treatment of mild infection in ambulatory
patients, and in combination with other medical regimens in treatment of
patients with severe disease. These drugs also continue to be clinically
utilized in hospitalized patients around the globe, often without
continuous telemetry due to lack of resources. Concern regarding use of
hydroxychloroquine without adequate rhythm monitoring in clinical trials
has been recently expressed.1 A review of
clinicaltrials.gov at the time of submission of this correspondence
reveals actively recruiting trials of combined
hydroxychloroquine/azithromycin with or without additional COVID-19
therapies, for both ambulatory and hospitalized patients within and
outside the US. The potential for hydroxychloroquine and azithromycin to
cause QT prolongation is counterbalanced by very low risk of
pro-arrhythmia in the general population, and emerging evidence of
relatively low risk of Torsades de Pointes (TdP) in COVID-19
patients.2,3,4,5 Thus delineation of the determinants
of significant QTc prolongation and pro-arrhythmic risk for
hydroxychloroquine/azithromycin is very important, especially given
mounting evidence of inefficacy in COVID-19 treatment.