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, 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. Funding: The study was supported by internal institutional funds of the Hamad Medical Corporation (government health service of the State of Qatar).

Hydroxychloroquine with or without azithromycin for treatment of early SARS-CoV-2 infection among high-risk outpatient adults: A randomized clinical trial

“…Our results indicate that HCQ/AZ does not hasten viral clearance as was hypothesized based on observational studies [ 8 , 9 ], similar to findings by Omrani et al. [14] . Perhaps more importantly, we did not find that HCQ/AZ decreases time to resolution of COVID-19 symptoms, a finding which is consistent with data from randomized controlled trials in hospitalized Brazilian patients with moderate or severe disease [ 24 , 25 ].…”

“…A third trial randomized, placebo-controlled trial by Omrani et al. showed HCQ with or without AZ was not associated with a difference in proportion of participants with viral clearance at day 6, among healthy young men recruited within one day of symptom onset [14] . The current trial extends these findings in a population enriched with high-risk participants with laboratory-confirmed infection and provides daily viral shedding and granular detail on COVID-19 symptoms, along with careful safety monitoring.…”

“…Three randomized trials of HCQ treatment of COVID-19 in outpatients have been performed in predominantly younger populations without co-morbidities associated with severe COVID-19. These trials showed that HCQ did not decrease the duration of COVID-19 symptoms [ 12 , 13 ], or decrease the quantity of SARS-CoV-2 detected in nasal swabs [13] and a third trial of HCQ with or without AZ did not show a significant difference in proportion of participants with viral clearance at study day 6 [14] . We hypothesized that studying HCQ with or without AZ in an outpatient population enriched for those at high-risk for progression to COVID-19 would provide additional information about the utility of these interventions to prevent progression to lower respiratory tract infection (LRTI), hospitalization, or death.…”

A Systematic Review and Network Meta-Analysis for COVID-19 Treatments

“…A total of 74 studies 2, 5, 15-18, 36-39, 41-44, 47-54, 56, 57, 59-63, 65-67, 69, 70, 72, 74-76, 78, 79, 82, 83, 85, 87, 88, 90-92, 94-97, 99, 100, 103-121, 125 including 48622 patients reported all-cause mortality. After filtering out treatments with small sample size following the specified criteria, the network included azithromycin, hydroxychloroquine, hydroxychloroquine plus azithromycin, colchicine, arbidol (umifenovir), favipiravir, remdesivir, lopinavir/ritonavir, convalescent plasma, methylprednisolone, dexamethasone, hydrocortisone, immunoglobulin, interferon beta, recombinant human granulocyte colony-stimulating factor (GCSF), tocilizumab, vitamin D 3 , baricitinib plus remdesivir, sulodexide and SOC.…”

Analysis of the performances of the Covid-19 therapeutic approaches in the United Arab Emirates

“…Controversial results are limited to the late cases, with however 74% of the studies still reporting positive effects. The use in early stages, generally supported in the literature [44][45][46][47][48][49][50][51][52], is also adopted with success in [4].…”