Randomized double-blinded placebo-controlled trial of hydroxychloroquine with or without azithromycin for virologic cure of non-severe Covid-19.

ABSTRACT

BACKGROUND: Hydroxychloroquine (HC) ± azithromycin (AZ) is widely used for Covid-19. The Qatar Prospective RCT of Expediting Coronavirus Tapering (Q-PROTECT) aimed to assess virologic cure rates of HC±AZ in cases of low-acuity Covid-19. METHODS: Q-PROTECT employed a prospective, placebo-controlled design with blinded randomization to three parallel arms placebo, oral HC (600 mg daily for one week), or oral HC plus oral AZ (500 mg day one, 250 mg daily on days two through five). At enrollment, non-hospitalized participants had mild or no symptoms and were within a day of Covid-19 positivity by polymerase chain reaction (PCR). After six days, intent-to-treat (ITT) analysis of the primary endpoint of virologic cure was assessed using binomial exact 95% confidence intervals (CIs) and χ2 testing. (ClinicalTrials.gov NCT04349592, trial status closed to new participants.). FINDINGS: The study enrolled 456 participants (152 in each of three groups HC+AZ, HC, placebo) between 13 April and 1 August 2020. HC+AZ, HC, and placebo groups had 6 (3·9%), 7 (4·6%), and 9 (5·9%) participants go off study medications before completing the medication course (p = 0·716). Day six PCR results were available for all 152 HC+AZ participants, 149/152 (98·0%) HC participants, and 147/152 (96·7%) placebo participants. Day six ITT analysis found no difference (p = 0·821) in groups' proportions achieving virologic cure HC+AZ 16/152 (10·5%), HC 19/149 (12·8%), placebo 18/147 (12·2%). Day 14 assessment also showed no association (p = 0·072) between study group and viral cure HC+AZ 30/149 (20·1%,), HC 42/146 (28·8%), placebo 45/143 (31·5%). There were no serious adverse events. INTERPRETATION: HC±AZ does not facilitate virologic cure in patients with mild or asymptomatic Covid-19. FUNDING: The study was supported by internal institutional funds of the Hamad Medical Corporation (government health service of the State of Qatar).