Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis

Original: Lancet 22 May 2020

Author(s): Mehra MR, Desai SS, Ruschitzka F et al

Reviewer: Stylianos Loukides, e-Learning Director

Published: 24 May, 2020

Considering the current therapeutic strategies against COVID-19, the combination Hydroxychloroquine or chloroquine with macrolide is recommended. However, we have to confess that the absence of an effective treatment has led clinicians to redirect drugs that are known to be effective for other medical conditions to the treatment of COVID-19. Another important issue is the lacking of well designed studies. In this real life study a multinational registry analysis of the use of hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19 was recorded.

The registry comprised data from 671 hospitals in six continents. 96032 patients were hospitalised during the study period and met the inclusion criteria. Of these, 14888 patients were in the treatment groups (1868 received chloroquine, 3783 received chloroquine with a macrolide, 3016 received hydroxychloroquine, and 6221 received hydroxychloroquine with a macrolide) and 81144 patients were in the control group. 10698 (11.1%) patients died in hospital. After controlling for multiple confounding factors (age, sex, race or ethnicity, body-mass index, underlying cardiovascular disease and its risk factors, diabetes, underlying lung disease, smoking, immunosuppressed condition, and baseline disease severity), when compared with mortality in the control group (9.3%), hydroxychloroquine (18.0%; hazard ratio 1.335, 95% CI 1.223–1.457), hydroxychloroquine with a macrolide (23.8%; 1.447, 1.368–1.531), chloroquine (16.4%; 1.365, 1.218–1.531), and chloroquine with a macrolide (22.2%; 1.368, 1.273–1.469) were each independently associated with an increased risk of in-hospital mortality. Furthermore all hydroxychloroquine based regimens were independently associated with an increased risk of de-novo ventricular arrhythmia during hospitalisation.

Do we treat our patients in a wrong way? Definitely no. During the pandemic clinicians and researchers failed to provide a well designed randomized trial for an effective and simultaneously safe treatment. Additionally, the primary outcome must be solely dedicated to mortality. Any other parameters must represent secondary outcomes.

Another critical point is the selection of patients and the clinical phase where the drug is initiated. In the onset of symptoms or during deterioration? Do we treat our patients with delay? I strongly believe that we have to create an algorithm where laboratory, radiological, clinical findings in combination with the clinical phase and the underlying factors that driven severity must be involved. Until then, the best supportive care, is the only factor that could change the negative prognosis of the disease.

Respiratory digests
Respiratory infections