COVID-19 Evidence Alerts
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Current best evidence for clinical care (more info)

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Primary Prevention Bartoszko JJ, Siemieniuk RAC, Kum E, et al. Prophylaxis against covid-19: living systematic review and network meta-analysis. BMJ. 2021 Apr 26;373:n949. doi: 10.1136/bmj.n949.
Abstract

OBJECTIVE: To determine and compare the effects of drug prophylaxis on SARS-CoV-2 infection and covid-19.

DESIGN: Living systematic review and network meta-analysis.

DATA SOURCES: World Health Organization covid-19 database, a comprehensive multilingual source of global covid-19 literature to 25 March 2021, and six additional Chinese databases to 20 February 2021.

STUDY SELECTION: Randomised trials of people at risk of covid-19 who were assigned to receive prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles.

METHODS: Random effects bayesian network meta-analysis was performed after duplicate data abstraction. Included studies were assessed for risk of bias using a modification of the Cochrane risk of bias 2.0 tool, and certainty of evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) approach.

RESULTS: The first iteration of this living network meta-analysis includes nine randomised trials-six of hydroxychloroquine (n=6059 participants), one of ivermectin combined with iota-carrageenan (n=234), and two of ivermectin alone (n=540), all compared with standard care or placebo. Two trials (one of ramipril and one of bromhexine hydrochloride) did not meet the sample size requirements for network meta-analysis. Hydroxychloroquine has trivial to no effect on admission to hospital (risk difference 1 fewer per 1000 participants, 95% credible interval 3 fewer to 4 more; high certainty evidence) or mortality (1 fewer per 1000, 2 fewer to 3 more; high certainty). Hydroxychloroquine probably does not reduce the risk of laboratory confirmed SARS-CoV-2 infection (2 more per 1000, 18 fewer to 28 more; moderate certainty), probably increases adverse effects leading to drug discontinuation (19 more per 1000, 1 fewer to 70 more; moderate certainty), and may have trivial to no effect on suspected, probable, or laboratory confirmed SARS-CoV-2 infection (15 fewer per 1000, 64 fewer to 41 more; low certainty). Owing to serious risk of bias and very serious imprecision, and thus very low certainty of evidence, the effects of ivermectin combined with iota-carrageenan on laboratory confirmed covid-19 (52 fewer per 1000, 58 fewer to 37 fewer), ivermectin alone on laboratory confirmed infection (50 fewer per 1000, 59 fewer to 16 fewer) and suspected, probable, or laboratory confirmed infection (159 fewer per 1000, 165 fewer to 144 fewer) remain very uncertain.

CONCLUSIONS: Hydroxychloroquine prophylaxis has trivial to no effect on hospital admission and mortality, probably increases adverse effects, and probably does not reduce the risk of SARS-CoV-2 infection. Because of serious risk of bias and very serious imprecision, it is highly uncertain whether ivermectin combined with iota-carrageenan and ivermectin alone reduce the risk of SARS-CoV-2 infection.

SYSTEMATIC REVIEW REGISTRATION: This review was not registered. The protocol established a priori 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
Infectious Disease
Public Health
Hospital Doctor/Hospitalists
Internal Medicine
Occupational and Environmental Health
Comments from MORE raters

Infectious Disease rater

Nil

Occupational and Environmental Health rater

Prophylaxis for preventing Covid-19 infection, the jury is in. Despite the short timeframe that we have been studying and treating Covid-19 infections, there is sufficient high quality research on hydrochloroquine and chloroquine to demonstrate is lack of utility as a prophylactic or active treatment alone or in combination. Other agents, such as Ivermectin have not been well studied sufficiently not be conclusive, but appear ineffective, as well.

Occupational and Environmental Health rater

This study uses a complex methodology to assess the potential benefits of different medication regimens to prevent SARS-CoV 2 infection. Th results indicate no significant benefit for hydroxy chloroquine and probably no benefit for ivermectin with or without iota-carageenan. As this is a living systematic study, we should expect additional updates in the near future.

Public Health rater

This relevant article precisely provides all the uncertainty on the pharmacological prevention of Covid-19 infections. Although the yields are inconclusive, and need a programmed update, the study proves argument to avoids the prophylactic use of Hydroxychloroquine and ivermectin for SARS-2 infections.