Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials
Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Springer Nature
2021
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| _version_ | 1797099670363701248 |
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| author | Axfors, C Schmitt, AM Janiaud, P Van't Hooft, J Abd-Elsalam, S Abdo, EF Abella, BS Akram, J Amaravadi, RK Angus, DC Arabi, YM Azhar, S Baden, LR Baker, AW Belkhir, L Benfield, T Berrevoets, MAH Chen, C-P Chen, T-C Cheng, S-H Cheng, C-Y Chung, W-S Cohen, YZ Cowan, LN Dalgard, O de Almeida E Val, FF de Lacerda, MVG de Melo, GC Derde, L Dubee, V Elfakir, A Gordon, AC Hernandez-Cardenas, CM Hills, T Hoepelman, AIM Huang, Y-W Igau, B Jin, R Jurado-Camacho, F Khan, KS Kremsner, PG Kreuels, B Kuo, C-Y Le, T Lin, Y-C Lin, W-P Lin, T-H Lyngbakken, MN McArthur, C McVerry, BJ Nichol, A |
| author_facet | Axfors, C Schmitt, AM Janiaud, P Van't Hooft, J Abd-Elsalam, S Abdo, EF Abella, BS Akram, J Amaravadi, RK Angus, DC Arabi, YM Azhar, S Baden, LR Baker, AW Belkhir, L Benfield, T Berrevoets, MAH Chen, C-P Chen, T-C Cheng, S-H Cheng, C-Y Chung, W-S Cohen, YZ Cowan, LN Dalgard, O de Almeida E Val, FF de Lacerda, MVG de Melo, GC Derde, L Dubee, V Elfakir, A Gordon, AC Hernandez-Cardenas, CM Hills, T Hoepelman, AIM Huang, Y-W Igau, B Jin, R Jurado-Camacho, F Khan, KS Kremsner, PG Kreuels, B Kuo, C-Y Le, T Lin, Y-C Lin, W-P Lin, T-H Lyngbakken, MN McArthur, C McVerry, BJ Nichol, A |
| author_sort | Axfors, C |
| collection | OXFORD |
| description | Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities. |
| first_indexed | 2024-03-07T05:26:57Z |
| format | Journal article |
| id | oxford-uuid:e0e60d96-b0bc-4fb9-bf20-502e3d538451 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:26:57Z |
| publishDate | 2021 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:e0e60d96-b0bc-4fb9-bf20-502e3d5384512022-03-27T09:50:45ZMortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trialsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e0e60d96-b0bc-4fb9-bf20-502e3d538451EnglishSymplectic ElementsSpringer Nature2021Axfors, CSchmitt, AMJaniaud, PVan't Hooft, JAbd-Elsalam, SAbdo, EFAbella, BSAkram, JAmaravadi, RKAngus, DCArabi, YMAzhar, SBaden, LRBaker, AWBelkhir, LBenfield, TBerrevoets, MAHChen, C-PChen, T-CCheng, S-HCheng, C-YChung, W-SCohen, YZCowan, LNDalgard, Ode Almeida E Val, FFde Lacerda, MVGde Melo, GCDerde, LDubee, VElfakir, AGordon, ACHernandez-Cardenas, CMHills, THoepelman, AIMHuang, Y-WIgau, BJin, RJurado-Camacho, FKhan, KSKremsner, PGKreuels, BKuo, C-YLe, TLin, Y-CLin, W-PLin, T-HLyngbakken, MNMcArthur, CMcVerry, BJNichol, ASubstantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities. |
| spellingShingle | Axfors, C Schmitt, AM Janiaud, P Van't Hooft, J Abd-Elsalam, S Abdo, EF Abella, BS Akram, J Amaravadi, RK Angus, DC Arabi, YM Azhar, S Baden, LR Baker, AW Belkhir, L Benfield, T Berrevoets, MAH Chen, C-P Chen, T-C Cheng, S-H Cheng, C-Y Chung, W-S Cohen, YZ Cowan, LN Dalgard, O de Almeida E Val, FF de Lacerda, MVG de Melo, GC Derde, L Dubee, V Elfakir, A Gordon, AC Hernandez-Cardenas, CM Hills, T Hoepelman, AIM Huang, Y-W Igau, B Jin, R Jurado-Camacho, F Khan, KS Kremsner, PG Kreuels, B Kuo, C-Y Le, T Lin, Y-C Lin, W-P Lin, T-H Lyngbakken, MN McArthur, C McVerry, BJ Nichol, A Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials |
| title | Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials |
| title_full | Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials |
| title_fullStr | Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials |
| title_full_unstemmed | Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials |
| title_short | Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials |
| title_sort | mortality outcomes with hydroxychloroquine and chloroquine in covid 19 from an international collaborative meta analysis of randomized trials |
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