Hydroxychloroquine for the treatment of severe respiratory infection by COVID-19: A randomized controlled trial

Abstract

Introduction The novel coronavirus pandemic (COVID–19) represents a major public health problem and it is key to find a treatment that reduces mortality. Our objective was to estimate whether treatment with 400 mg/day of Hydroxychloroquine for 10 days reduces in-hospital mortality in subjects with severe respiratory disease due to COVID-19 compared with placebo. Material and methods A double-blind, randomized, placebo-controlled trial to evaluate the safety and efficacy of Hydroxychloroquine for the treatment of severe disease by COVID-19 through an intention-to-treat analysis. Eligible for the study were adults aged more than 18 years with COVID-19 confirmed by RT-PCR and lung injury requiring hospitalization with or without mechanical ventilation. Primary outcome was 30-day mortality. Secondary outcomes: days of mechanical ventilation, days of hospitalization and cumulative incidence of serious adverse events. Results A total of 214 patients with COVID-19 were recruited, randomized and analyzed. They were hypoxemic with a mean SpO2 of 65% ± 20, tachycardic (pulse rate 108±17 min-1) and tachypneic (32 ±10 min-1); 162 were under mechanical ventilation at randomization. Thirty-day mortality was similar in both groups (38% in Hydroxychloroquine vs. 41% in placebo, hazard ratio [HR] 0.88, 95% Confidence Interval [95%CI] 0.51–1.53). In the surviving participants, no significant difference was found in secondary outcomes. Conclusion No beneficial effect or significant harm could be demonstrated in our randomized controlled trial including 214 patients, using relatively low doses of Hydroxychloroquine compared with placebo in hospitalized patients with severe COVID-19.

Hydroxychloroquine versus placebo in the treatment of non-hospitalised patients with COVID-19 (COPE – Coalition V): A double-blind, multicentre, randomised, controlled trial

“… 20 , 21 , 22 Furthermore, among adults hospitalised with respiratory illness from COVID-19, treatment with hydroxychloroquine did not significantly improve clinical status, mortality rates or need for invasive mechanical ventilation at 14 days compared with placebo or control. 23 , 24 , 25 …”

Hydroxychloroquine/chloroquine and the risk of acute kidney injury in COVID-19 patients: a systematic review and meta-analysis

“…After excluding 134 with different outcomes, 33 with different interventions, ten with different populations, and three with different study types, we finally included 20 studies [ 24–43 ] for the current systematic review, with a kappa value of 0.85 between the two reviewers ( Figure S1, Supplementary Appendix ). The updated search in 31, Dec 2021 (10 July, 2021 to 31, Dec 2021) resulted in 648 records, 72 were identified as duplicates, and 1 RCT [ 44 ] was identified as new studies that included in current meta-analysis.…”

Hydroxychloroquine/chloroquine for the treatment of hospitalized patients with COVID-19: An individual participant data meta-analysis

“…Consequently, adequate power to reach robust conclusions regarding efficacy and safety of HCQ/CQ was no longer attainable for many incomplete trials; moreover, effect estimates in published trials were accompanied by wide confidence intervals. Nevertheless, at least 11 additional RCTs published later in the pandemic found similar results [20][21][22][23][24][25][26][27][28][29][30].…”

“…This IPD meta-analysis of 8 RCTs in 770 hospitalized COVID-19 patients comparing HCQ/CQ and control treatment confirms results of at least 16 published RCTs showing no benefit of HCQ/CQ. 18,[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] Neither the primary outcome measurement, ordinal scale at 28-35 days, nor the secondary outcome measurement, mortality at 28-35 days, was improved with HCQ/CQ in the pooled study population. We found no subgroup in which appreciable benefits could be observed for the primary outcome.…”

“…Nevertheless, at least 11 additional RCTs published later in the pandemic found similar results. [24][25][26][27][28][29][30][31][32][33][34] The purpose of this study was to ensure utilization of data from unpublished RCTs evaluating HCQ/CQ by combining them with published data, and to synthesize evidence on HCQ/CQ efficacy and safety in hospitalized COVID-19 patients, overall and in subpopulations of interest, by conducting an individual participant data (IPD) meta-analysis.…”