tetano
Editor, Senior Moderator
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[SUP] 1 2 3 [/SUP], Gilmar Reis[SUP] 4 5 [/SUP], David R Boulware[SUP] 6 [/SUP], Adam M Spivak[SUP] 7 [/SUP], Ammar Sarwar[SUP] 8 [/SUP], Christine Johnston[SUP] 9 [/SUP], Brandon Webb[SUP] 10 [/SUP], Michael D Hill[SUP] 11 [/SUP], Davey Smith[SUP] 12 [/SUP], Peter Kremsner[SUP] 13 14 [/SUP], Marla Curran[SUP] 15 [/SUP], David Carter[SUP] 16 [/SUP], Jim Alexander[SUP] 15 [/SUP], Marc Corbacho[SUP] 1 [/SUP], Todd C Lee[SUP] 6 [/SUP], Katherine Huppler Hullsiek[SUP] 6 [/SUP], Emily G McDonald[SUP] 17 [/SUP], Rachel Hess[SUP] 7 [/SUP], Michael Hughes[SUP] 8 [/SUP], Jared M Baeten[SUP] 9 [/SUP], Ilan Schwartz[SUP] 18 [/SUP], Luanne Metz[SUP] 11 [/SUP], Lawrence Richer[SUP] 18 [/SUP], Kara W Chew[SUP] 19 [/SUP], Eric Daar[SUP] 20 [/SUP], David Wohl[SUP] 21 [/SUP], Michael Dunne[SUP] 15 [/SUP]
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.
. 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[SUP] 1 2 3 [/SUP], Gilmar Reis[SUP] 4 5 [/SUP], David R Boulware[SUP] 6 [/SUP], Adam M Spivak[SUP] 7 [/SUP], Ammar Sarwar[SUP] 8 [/SUP], Christine Johnston[SUP] 9 [/SUP], Brandon Webb[SUP] 10 [/SUP], Michael D Hill[SUP] 11 [/SUP], Davey Smith[SUP] 12 [/SUP], Peter Kremsner[SUP] 13 14 [/SUP], Marla Curran[SUP] 15 [/SUP], David Carter[SUP] 16 [/SUP], Jim Alexander[SUP] 15 [/SUP], Marc Corbacho[SUP] 1 [/SUP], Todd C Lee[SUP] 6 [/SUP], Katherine Huppler Hullsiek[SUP] 6 [/SUP], Emily G McDonald[SUP] 17 [/SUP], Rachel Hess[SUP] 7 [/SUP], Michael Hughes[SUP] 8 [/SUP], Jared M Baeten[SUP] 9 [/SUP], Ilan Schwartz[SUP] 18 [/SUP], Luanne Metz[SUP] 11 [/SUP], Lawrence Richer[SUP] 18 [/SUP], Kara W Chew[SUP] 19 [/SUP], Eric Daar[SUP] 20 [/SUP], David Wohl[SUP] 21 [/SUP], Michael Dunne[SUP] 15 [/SUP]
Affiliations
- PMID: 36601684
- DOI: 10.1111/cts.13468
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.