Does hydroxychloroquine reduce mortality in patients with COVID‐19? A meta‐analysis with trial sequential analysis

• Published in: International Journal of Clinical Practice Vol. 75; no. 10; pp. e14448 - n/a
• Main Authors: Chen, Po‐Huang, Jhou, Hong‐Jie, Ou‐Yang, Liang‐Jun, Lee, Cho‐Hao
• Format: Journal Article Web Resource
• Language: English
• Published: London Hindawi Limited 01.10.2021; John Wiley & Sons, Inc; John Wiley and Sons Inc
• Subjects: COVID-19; Hydroxychloroquine; Letter; LETTERS; Meta-analysis
• ISSN: 1368-5031; 1742-1241
• DOI: 10.1111/ijcp.14448

Hydroxychloroquine, a classic drug derived from chloroquine for rheumatological diseases, has shown activity against the novel coronavirus in vitro and been authorised in some national regulatory agencies to treat patients with COVID-19.1, 2 However, some studies reported no effect on the intubation rate or mortality.3 We therefore performed a meta-analysis to evaluate the effects of hydroxychloroquine on overall mortality in patients with COVID-19. Included studies of the use of hydroxychloroquine regarding mortality First author Journal Type Patient characteristics Treatment Randomised control trial Chen et al PMID: 32391667 J Zhejiang Univ (Med Sci) Randomised control trial Hospitalised patients (exclude severe symptoms) HCQ 400 mg/d for 5 d Skipper et al PMID: 32673060 Annals of Internal Medicine Randomised control trial Non-hospitalised adults with early COVID-19 HCQ (800 mg once, followed by 60 mg in 6-8 h, then 600 mg daily for 4 more days) Cavalcanti et al PMID: 32 706 953 NEJM Randomised control trial Mild-to-moderate hospitalised patients HCQ 800 mg/d for 7 d with/without AZI RECOVERY Collaborative Group PMID: 33031652 N Engl J Med Randomised control trial Hospitalised patients HCQ 1600 mg on day 1, followed by 800 mg/d for 9 d Abd-Elsalam et al PMID: 32828135 The American Journal of Tropical Medicine and Hygiene Randomised control trial Hospitalised patients HCQ 800 mg on day 1, followed by 400 mg/d for 15 d Mitjà et al PMID: 32674126 Clinical Infectious Diseases Randomised control trial Non-hospitalised adults with mild COVID-19 HCQ 800 mg on day 1, followed by 400 mg/d for 6 d Tang et al PMID: 32409561 BMJ Randomised control trial Mild-to-moderate hospitalised patients HCQ 1200 mg/d for 3 d, followed by 800 mg/d for 2-3 wk WHO Solidarity Trial Consortium PMID: 33264556 N Engl J Med Randomised control trial Hospitalised patients HCQ 2400 mg on day 1, followed by 400 mg/d for 9 d Non-randomised clinical trial Gautret et al PMID: 32205204 Int J Antimicrob Agents Non-randomised clinical trial Mild symptoms hospitalised patients HCQ 600 mg/d for 10 d with AZI Rosenberg et al PMID: 32392282 JAMA Cohort/observational Hospitalised patients HCQ with/without AZI Mahevas et al PMID: 32554525 BMJ Cohort/observational Mild-to-moderate hospitalised patients HCQ 600 mg/d Geleris et al PMID: 32379955 N Engl J Med Cohort/observational Moderate-to-severe respiratory illness hospitalised patients HCQ 1200 mg on day 1, followed by 400 mg/d for 4 additional days with/without AZI Yu et al PMID: 32418114 Sci. A previous meta-analysis evaluating the effects of hydroxychloroquine in the treatment of COVID-19 was characterised by insufficient and often conflicting evidence.4 However, with numerous studies emerging since its publication, the previous meta-analysis, which included limited studies, does not reflect the current understanding of the literature. [...]we performed an updated meta-analysis that showed no evidence of benefit for hydroxychloroquine in reducing mortality.4 Even if the meta-analysis alone concluded that the intervention has no effect, it still could have insufficient statistical power to investigate the true effects.5 TSA is a realistic and reliable tool to test whether the meta-analysis is adequately powered or reports spurious results because of systematic bias or random errors. [...]our meta-analysis with TSA suggests that the use of hydroxychloroquine in patients with COVID-19 has no benefit in reducing overall mortality.