COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

Treatment Siemieniuk RA, Bartoszko JJ, Ge L, et al. Drug treatments for covid-19: living systematic review and network meta-analysis. BMJ. 2020 Jul 30;370:m2980. doi: 10.1136/bmj.m2980.
Abstract

OBJECTIVE: To compare the effects of treatments for coronavirus disease 2019 (covid-19).

DESIGN: Living systematic review and network meta-analysis.

DATA SOURCES: US Centers for Disease Control and Prevention COVID-19 Research Articles Downloadable Database, which includes 25 electronic databases and six additional Chinese databases to 20 July 2020.

STUDY SELECTION: Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles.

METHODS: After duplicate data abstraction, a bayesian random effects network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance.

RESULTS: 23 randomised controlled trials were included in the analysis performed on 26 June 2020. The certainty of the evidence for most comparisons was very low because of risk of bias (lack of blinding) and serious imprecision. Glucocorticoids were the only intervention with evidence for a reduction in death compared with standard care (risk difference 37 fewer per 1000 patients, 95% credible interval 63 fewer to 11 fewer, moderate certainty) and mechanical ventilation (31 fewer per 1000 patients, 47 fewer to 9 fewer, moderate certainty). These estimates are based on direct evidence; network estimates for glucocorticoids compared with standard care were less precise because of network heterogeneity. Three drugs might reduce symptom duration compared with standard care: hydroxychloroquine (mean difference -4.5 days, low certainty), remdesivir (-2.6 days, moderate certainty), and lopinavir-ritonavir (-1.2 days, low certainty). Hydroxychloroquine might increase the risk of adverse events compared with the other interventions, and remdesivir probably does not substantially increase the risk of adverse effects leading to drug discontinuation. No other interventions included enough patients to meaningfully interpret adverse effects leading to drug discontinuation.

CONCLUSION: Glucocorticoids probably reduce mortality and mechanical ventilation in patients with covid-19 compared with standard care. The effectiveness of most interventions is uncertain because most of the randomised controlled trials so far have been small and have important study limitations.

SYSTEMATIC REVIEW REGISTRATION: This review was not registered. The protocol is included as a supplement.

READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

Ratings
Discipline / Specialty Area Score
Intensivist/Critical Care
Hospital Doctor/Hospitalists
Internal Medicine
Infectious Disease
Respirology/Pulmonology
Comments from MORE raters

Intensivist/Critical Care rater

This is an important systematic review of COVID-19 therapies studied in randomized controlled trials and also it is an important example of a living systematic review that is particularly relevant in this quickly changing pandemic landscape and will be updated for up to two years. The authors used the CDC database as well as a Chinese database to identify relevant articles and perform the meta-analysis. They identify steroids (dexamethasone) as a therapy that decreases mortality as well as mechanical ventilation. They also identified the small size of existing trials as a limitation. The limitation of the small size of the trials may change as the review is updated.

Respirology/Pulmonology rater

This is an interesting meta analysis and summary of the literature to date. The utility of this document will be that it could become a resource for continually updated information as other trials come out and the authors update the document. It is a BMJ "living document".