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, 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

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).

Keywords: Azithromycin; Covid-19; Hyodroxychloroquine.

Conflict of interest statement

The authors have no financial or personal relationships with other people or organizations that could represent a conflict of interest.

© 2020 The Authors.

Figures

Fig. 1
Fig. 1
Trial profile.
Fig. 2
Fig. 2
Primary outcome of virologic cure at day six.
Fig. 3
Fig. 3
Secondary outcome of virologic cure at day 14.

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Source: PubMed

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