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Efficacy of chloroquine or hydroxychloroquine in COVID-19 patients: a systematic review and meta-analysis.

ABSTRACT: OBJECTIVES:Clinical studies of chloroquine (CQ) and hydroxychloroquine (HCQ) in COVID-19 disease reported conflicting results. We sought to systematically evaluate the effect of CQ and HCQ with or without azithromycin on outcomes of COVID-19 patients. METHODS:We searched multiple databases, preprints and grey literature up to 17 July 2020. We pooled only adjusted-effect estimates of mortality using a random-effect model. We summarized the effect of CQ or HCQ on viral clearance, ICU admission/mechanical ventilation and hospitalization. RESULTS:Seven randomized clinical trials (RCTs) and 14 cohort studies were included (20?979 patients). Thirteen studies (1 RCT and 12 cohort studies) with 15?938 hospitalized patients examined the effect of HCQ on short-term mortality. The pooled adjusted OR was 1.05 (95% CI 0.96-1.15, I2?=?0%). Six cohort studies examined the effect of the HCQ+azithromycin combination with a pooled adjusted OR of 1.32 (95% CI 1.00-1.75, I2?=?68.1%). Two cohort studies and four RCTs found no effect of HCQ on viral clearance. One small RCT demonstrated improved viral clearance with CQ and HCQ. Three cohort studies found that HCQ had no significant effect on mechanical ventilation/ICU admission. Two RCTs found no effect for HCQ on hospitalization risk in outpatients with COVID-19. CONCLUSIONS:Moderate certainty evidence suggests that HCQ, with or without azithromycin, lacks efficacy in reducing short-term mortality in patients hospitalized with COVID-19 or risk of hospitalization in outpatients with COVID-19.

SUBMITTER: Kashour Z

PROVIDER: S-EPMC7665543 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Efficacy of chloroquine or hydroxychloroquine in COVID-19 patients: a systematic review and meta-analysis.

Kashour Zakariya Z Riaz Muhammad M Garbati Musa A MA AlDosary Oweida O Tlayjeh Haytham H Gerberi Dana D Murad M Hassan MH Sohail M Rizwan MR Kashour Tarek T Tleyjeh Imad M IM

The Journal of antimicrobial chemotherapy 20210101 1

<h4>Objectives</h4>Clinical studies of chloroquine (CQ) and hydroxychloroquine (HCQ) in COVID-19 disease reported conflicting results. We sought to systematically evaluate the effect of CQ and HCQ with or without azithromycin on outcomes of COVID-19 patients.<h4>Methods</h4>We searched multiple databases, preprints and grey literature up to 17 July 2020. We pooled only adjusted-effect estimates of mortality using a random-effect model. We summarized the effect of CQ or HCQ on viral clearance, IC ...[more]

PMID: 33031488

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Project description:Repurposed drugs like hydroxycloroquine (HCQ) and chloroquine (CQ) are being tested for potential therapeutic role in COVID-19. We aimed to evaluate efficacy and safety of HCQ and CQ in COVID-19. Using PubMed, EMBASE, medRxiv, Google Scholar, clinicaltrials.gov, electronic search was carried out to identify relevant articles till June 2020 with re-evaluation in last week of November 2020. Observational and interventional clinical studies comparing efficacy of CQ or HCQ to standard management or other drug/s for SARS-CoV-2 infection patients were included. Cochrane review manager version 5.3 was used for synthesis of meta-analysis results. For randomized controlled trials, risk of bias was assessed using Cochrane Collaboration risk of bias assessment tool, version 2.0 (ROB-2). ROBINS-I was used for quality assessment of observational studies. Overall evidence quality generated by review was graded as per GRADE Recommendation. A total of 903 studies were screened. Nineteen studies were included in synthesis of meta-analysis with total of 4,693, 1,626, and 6,491 patients in HCQ/CQ, HCQ/CQ + AZ and control groups, respectively. HCQ/CQ treatment was associated with significantly increased rates of virological cure (OR = 2.08, 95%CI = 1.36-3.17; P = 0.0007) and radiological cure (OR = 3.89, 95%CI = 1.35 - 11.23; P = 0.01) compared to control. HCQ/CQ had no difference in unadjusted mortality rate (unadjusted OR = 0.98 95% CI = 0.70-1.37, P = 0.89, random effect model) and adjusted hazard ratio for mortality (adjusted HR = 1.05, 95%CI = 0.86--1.29; P = 0.64). However, a significant increase in odds of disease progression (OR = 1.77, 95%CI = 1.46-2.13; P < 0.00001) and QT prolongation (OR = 11.15, 95%CI = 3.95-31.44; P < 0.00001) was noted. The results with HCQ/CQ and azithromycin combination were similar to HCQ/CQ mono-therapy. In the light of contemporary evidence on effectiveness of HCQ/CQ, judicious and monitored use of HCQ/CQ for treatment of COVID-19 patients is recommended in low to middle income countries with emphasis on no mortality benefit. Registration number of Systematic review. Register in PROSPERO database: cRD42020187710.

Project description:The coronavirus disease 19 (COVID-19) pandemic has caused significant morbidity and mortality worldwide and an effective treatment is needed. Chloroquine (CQ) and hydroxychloroquine (HCQ) have shown in vitro antiviral activity against SARS-CoV-2 which causes the disease, but the evidence from in vivo studies so far has been inconclusive.ObjectiveTo evaluate the efficacy and safety of CQ and HCQ in the treatment of COVID-19.Data sourcesWe systematically searched the PubMed, Embase, MEDLINE, Cochrane CENTRAL, CINAHL, Scopus, Joanna Briggs Institute Database, ClinicalTrials.gov, and Chinese Clinical Trial Registry (ChiCTR) for all articles published between 01 January 2020 to 15 September 2020 on CQ/HCQ and COVID-19 using a predefined search protocol; without any language restrictions. A search of grey literature repositories (New York Academy of Medicine Grey Literature and Open Grey), and pre-publication server deposits (medRxIV and bioRxIV) was also performed.Study selectionRandomized clinical trials (RCT) which compared CQ/HCQ to standard supportive therapy in treating COVID-19 were included.Data extraction and synthesisData were extracted from original publications by four independent reviewers. Risk of bias was assessed using the Cochrane Collaboration's assessment tool. Data were meta-analyzed using a random-effect models. Results are reported according to PRISMA guidelines. Main Outcome(s) and Measure(s): The primary prespecified efficacy outcome was all-cause mortality. The primary safety outcome was any adverse effect attributed to use of CQ/HCQ.ResultsEight RCTs were included and pooled in the mortality meta-analysis (6,592 unique participants; mean age = 59.4 years; 42% women). CQ/HCQ did not show any mortality benefit when compared to standard supportive therapy (Pooled Relative Risk [RR] 1.07; 95% CI = 0.97-1.18; I2 statistic = 0.00%). Sensitivity and sub-group analyses showed similar findings. Any adverse event was significantly higher in patients randomized to CQ/HCQ (RR = 2.51; 95% CI = 1.53-4.12; n = 1,818 patients), but the risk of developing severe adverse event was not statistically significant (RR = 0.99, 95% CI = 0.53-1.86; n = 6,456 patients).Conclusions and relevanceEvidence from currently published RCTs do not demonstrate any added benefit for the use of CQ or HCQ in the treatment of COVID-19 patients.

Dataset Information

Efficacy of chloroquine or hydroxychloroquine in COVID-19 patients: a systematic review and meta-analysis.

Publications

Efficacy of chloroquine or hydroxychloroquine in COVID-19 patients: a systematic review and meta-analysis.

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