key: cord-0991894-gkuto1la
authors: Chen, Po‐Huang; Jhou, Hong‐Jie; Ou‐Yang, Liang‐Jun; Lee, Cho‐Hao
title: Does hydroxychloroquine reduce mortality in patients with COVID‐19? A meta‐analysis with trial sequential analysis
date: 2021-09-16
journal: Int J Clin Pract
DOI: 10.1111/ijcp.14448
sha: 32d3733fc9c7d1ba44321fa900962b57b537a020
doc_id: 991894
cord_uid: gkuto1la

nan

The COVID-19 outbreak has caused an unprecedented global health and financial crisis. As of August 2020, more than 20 million people worldwide have been infected; however, specific treatments remain investigational. 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.

Furthermore, we employed trial sequential analysis (TSA) to verify whether the results of the meta-analysis were conclusive.

Comprehensive literature searches using PubMed, Google Scholar, MedRxiv and the preprints literature were undertaken for studies published up to February 2021, using the keywords "COVID-19", "hydroxychloroquine" and "mortality" with related MeSH terms. Two reviewers (PHC and HJJ) independently screened the titles and abstracts and extracted the data. Any discrepancy was solved by group discussion. A random-effects DerSimonian-Laird model was used to estimate the odds ratio (OR) with 95% confidence interval (CI). Heterogeneity across the studies was detected by I 2 > 50% and Cochran Q-test P < .1. Subgroup analyses were performed toward the study designs, the therapeutic regimens and the COVID-19 severities to detect clinical and statistical heterogeneity. All statistical analyses were performed using the "metafor" and "meta" packages of R software (version 3.6.1., R Foundation for Statistical Computing, Vienna, Austria) We constructed TSA boundaries according to the O'Brien-Fleming alpha-spending function with two-sided α = 5% and 1β = 80% power. We assumed a relative risk reduction by calculating from the mean of the event proportions F I G U R E 1 Trial sequential analysis in meta-analysis of overall mortality. In this figure, TSA showed that the Z-curve has crossed the required information size but has not crossed the conventional boundary, suggesting that the hydroxychloroquine treatment is no different from conventional therapy in reducing overall mortality. The result is conclusive and robust based on TSA. X-axis, accrued information size; Y-axis, cumulative Z-score; blue line, cumulative Z-value; solid red lines, trial sequential monitoring boundaries and the futility boundaries (threshold for statistical significance in TSA); horizontal dark red line, conventional boundaries (threshold for significance in conventional meta-analysis); and vertical solid red line, required information size. TSA, trial sequential analysis 

Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro

Cloroquina poderá ser usada em casos graves do coronavírus. Brazil: Ministério da Saúde

Observational study of hydroxychloroquine in hospitalized patients with covid-19

Hydroxychloroquine or chloroquine for treatment or prophylaxis of COVID-19: a living systematic review

Trial sequential analysis: adding a new dimension to meta-analysis

Trial sequential analysis may establish when firm evidence is reached in cumulative metaanalysis

The data that support the findings of this study are available from the corresponding author upon reasonable request. 

https://orcid.org/0000-0002-0280-6417Hong-Jie Jhou https://orcid.org/0000-0003-3304-4643