Randomized Controlled Trials of Early Ambulatory Hydroxychloroquine in the Prevention of COVID-19 Infection, Hospitalization, and Death: Meta-Analysis

Abstract

Objective--To determine if hydroxychloroquine (HCQ) reduces the incidence of new illness, hospitalization or death among outpatients at risk for or infected with SARS-CoV-2 (COVID-19). Design--Systematic review and meta-analysis of randomized clinical trials. Data sources--Search of MEDLINE, EMBASE, PubMed, medRxiv, PROSPERO, and the Cochrane Central Register of Controlled Trials. Also review of reference lists from recent meta-analyses. Study selection--Randomized clinical trials in which participants were treated with HCQ or placebo/standard-of-care for pre-exposure prophylaxis, post-exposure prophylaxis, or outpatient therapy for COVID-19. Methods--Two investigators independently extracted data on trial design and outcomes. Medication side effects and adverse reactions were also assessed. The primary outcome was COVID-19 hospitalization or death. When unavailable, new COVID-19 infection was used. We calculated random effects meta-analysis according to the method of DerSimonian and Laird. Heterogeneity between the studies was evaluated by calculation of Cochran Q and I2 parameters. An Egger funnel plot was drawn to investigate publication bias. We also calculated the fixed effects meta-analysis summary of the five studies. All calculations were done in Excel, and results were considered to be statistically significant at a two-sided threshold of P=.05. Results--Five randomized controlled clinical trials enrolling 5,577 patients were included. HCQ was associated with a 24% reduction in COVID-19 infection, hospitalization or death, P=.025 (RR, 0.76 [95% CI, 0.59 to 0.97]). No serious adverse cardiac events were reported. The most common side effects were gastrointestinal. Conclusion--Hydroxychloroquine use in outpatients reduces the incidence of the composite outcome of COVID-19 infection, hospitalization, and death. Serious adverse events were not reported and cardiac arrhythmia was rare. Systematic review registration--This review was not registered.

A Comprehensive Review of Viral Characteristics, Transmission, Pathophysiology, Immune Response, and Management of SARS-CoV-2 and COVID-19 as a Basis for Controlling the Pandemic

“…Despite the evidence against the use of chloroquine or hydroxychloroquine the controversy continues. A meta-analysis that was posted on September 30th 2020 on the medRxiv preprint server concluded that hydroxychloroquine use in outpatients reduced hospital stay and mortality despite none of the five RCTs included in the analysis individually demonstrating benefit (208).…”

Hydroxychloroquine in the treatment of outpatients with mildly symptomatic COVID-19: a multi-center observational study

“…To increase power and synthesize the current landscape, a meta-analysis of outpatient randomized controlled studies was conducted, examining prevention of COVID-19 in 2 trials, and reduced hospitalization or death 3 trials. Using a composite endpoint of reduced risk of infection or risk of hospitalization or death, Ladapo et al identified a significant benefit with early use of hydroxychloroquine among outpatients infected with SARS-CoV-2 [36]. Thus, the potential benefit of hydroxychloroquine in the early management of outpatients should be of great interest and the subject of continued rigorous investigation.…”

COVID-19 and immune-mediated inflammatory rheumatic diseases

“…Уже c начале пандемии COVID-19 возник интерес к хлорохину и гидроксихлорохину, синтетическим производным хинина (4-аминохинолиновые препараты), которые применяются в медицине более 70 лет -в начале для лечения малярии, а затем и широкого круга ИВРЗ [35] и обладают широким спектром антивоспалительных, иммуномодулирующих и антивирусных эффектов [35,36]. Хотя мета-анализы результатов рандомизированных клинических исследований (как правило, низкого качества) не подтвердили эффективность (снижение летальности) гидроксихлорохина у пациентов с тяжелым COVID-19 [37], имеются данные, что превентивное применение этого препарата у пациентов с легким и средне-тяжелым течением COVID-19 ассоциировалось со снижением риска госпитализации и даже летальности [38].…”