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Clin Transl Sci . Hydroxychloroquine for treatment of non-hospitalized adults with COVID-19: A meta-analysis of individual participant data of randomized trials

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  • Clin Transl Sci . Hydroxychloroquine for treatment of non-hospitalized adults with COVID-19: A meta-analysis of individual participant data of randomized trials


    Clin Transl Sci


    . 2023 Jan 4.
    doi: 10.1111/cts.13468. Online ahead of print.
    Hydroxychloroquine for treatment of non-hospitalized adults with COVID-19: A meta-analysis of individual participant data of randomized trials


    Oriol Mitjà 1 2 3 , Gilmar Reis 4 5 , David R Boulware 6 , Adam M Spivak 7 , Ammar Sarwar 8 , Christine Johnston 9 , Brandon Webb 10 , Michael D Hill 11 , Davey Smith 12 , Peter Kremsner 13 14 , Marla Curran 15 , David Carter 16 , Jim Alexander 15 , Marc Corbacho 1 , Todd C Lee 6 , Katherine Huppler Hullsiek 6 , Emily G McDonald 17 , Rachel Hess 7 , Michael Hughes 8 , Jared M Baeten 9 , Ilan Schwartz 18 , Luanne Metz 11 , Lawrence Richer 18 , Kara W Chew 19 , Eric Daar 20 , David Wohl 21 , Michael Dunne 15



    Affiliations

    Abstract

    Hydroxychloroquine (HCQ) was initially promoted as an oral therapy for early treatment of coronavirus disease 2019 (COVID-19). Conventional meta-analyses cannot fully address the heterogeneity of different designs and outcomes of randomized controlled trials (RCTs) assessing the efficacy of HCQ in outpatients with mild COVID-19. We conducted a pooled analysis of individual participant data from RCTs that evaluated the effect of HCQ on hospitalization and viral load reduction in outpatients with confirmed COVID-19. We evaluated the overall treatment group effect by log-likelihood ratio test (-2LL) from a generalized linear mixed model to accommodate correlated longitudinal binary data. The analysis included data from 11 RCTs. The outcome of virological effect, assessed in 1560 participants (N = 795 HCQ, N = 765 control), did not differ significantly between the two treatment groups (-2LL = 7.66; p = 0.18) when adjusting for cohort, duration of symptoms, and comorbidities. The decline in polymerase chain reaction positive tests from day 1 to 7 was 42.0 and 41.6 percentage points in the HCQ and control groups, respectively. Among the 2037 participants evaluable for hospitalization (N = 1058 HCQ, N = 979 control), we found no significant differences in hospitalization rate between participants receiving HCQ and controls (odds ratio 0.995; 95% confidence interval 0.614-1.610; -2LL = 0.0; p = 0.98) when adjusting for cohort, duration of symptoms, and comorbidities. This individual participant data meta-analysis of 11 HCQ trials that evaluated severe acute respiratory syndrome-coronavirus 2 viral clearance and COVID-19 hospitalization did not show a clinical benefit of HCQ. Our meta-analysis provides evidence to support the interruption in the use of HCQ in mild COVID-19 outpatients to reduce progression to severe disease.


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