Randomized double-blinded placebo-controlled trial of hydroxychloroquine with or without azithromycin for virologic cure of non-severe Covid-19
Ali S Omrani, Sameer A Pathan, Sarah A Thomas, Tim R E Harris, Peter V Coyle, Caroline E Thomas, Isma Qureshi, Zain A Bhutta, Naema Al Mawlawi, Reham Al Kahlout, Ashraf Elmalik, Aftab M Azad, Joanne Daghfal, Mulham Mustafa, Andrew Jeremijenko, Hussam Al Soub, Mohammed Abu Khattab, Muna Al Maslamani, Stephen H Thomas
EClinicalMedicine, doi:10.1016/j.eclinm.2020.100645
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, intentto-treat (ITT) analysis of the primary endpoint of virologic cure was assessed using binomial exact 95% confidence intervals (CIs) and x 2 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.
Author contributions Authors have made the following contributions consistent with ICJME recommendations for authorship: All authors made meaningful contributions to manuscript preparation, review, and editing. In addition, the authors made contributions as follows: -Stephen H. Thomas conceived the study, co-wrote the draft manuscript, and maintains overall responsibility for Q-PROTECT conduct and reporting. -Ali S. Omrani made critical contributions/modifications to the study design and execution plans, and co-wrote the initial manuscript draft. -Sameer A. Pathan led the execution stage of the study. -Sarah A. Thomas planned the randomization and allocation concealment approaches, performed the literature search and initialdraft manuscript writing relevant to cell biology of putative drug action mechanisms, executed data-sharing processes, and assisted with revision of the manuscript during the editorial review process. -Peter V. Coyle led the virology testing planning and execution and made key manuscript contributions in the arena of laboratory medicine. -Naema Al Mawlawi and Reham Al Kahlout managed the lab specimens, executed all PCR analysis, and arranged virologic reporting data -Tim R. E. Harris provided substantial manuscript editing, and coordinated physician resourcing for study participant accrual and data processing. -Caroline E. Thomas led planning of, and manuscript writing describing, data entry spreadsheet/source-table preparing of participants' data entry..
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