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Prophylaxis against covid-19 : living systematic review and network meta-analysis Bartoszko, Jessica J.; Siemieniuk, Reed A. C.; Kum, Elena; Qasim, Anila; Zeraatkar, Dena; Ge, Long; Han, Mi Ah; Sadeghirad, Behnam; Agarwal, Arnav; Agoritsas, Thomas; Chu, Derek K.; Couban, Rachel; Darzi, Andrea J.; Devji, Tahira; Ghadimi, Maryam; Honarmand, Kimia; Izcovich, Ariel; Khamis, Assem; Lamontagne, Francois; Loeb, Mark; Marcucci, Maura; McLeod, Shelley L.; Motaghi, Sharhzad; Murthy, Srinivas; Mustafa, Reem A.; Neary, John D.; Pardo-Hernandez, Hector; Rada, Gabriel; Rochwerg, Bram; Switzer, Charlotte; Tendal, Britta; Thabane, Lehana; Vandvik, Per O.; Vernooij, Robin W. M.; Viteri-García, Andrés; Wang, Ying; Yao, Liang; Ye, Zhikang; Guyatt, Gordon H.; Brignardello-Petersen, Romina
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 metaanalysis 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. Co nclusions 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.
Item Metadata
| Title |
Prophylaxis against covid-19 : living systematic review and network meta-analysis
|
| Creator |
Bartoszko, Jessica J.; Siemieniuk, Reed A. C.; Kum, Elena; Qasim, Anila; Zeraatkar, Dena; Ge, Long; Han, Mi Ah; Sadeghirad, Behnam; Agarwal, Arnav; Agoritsas, Thomas; Chu, Derek K.; Couban, Rachel; Darzi, Andrea J.; Devji, Tahira; Ghadimi, Maryam; Honarmand, Kimia; Izcovich, Ariel; Khamis, Assem; Lamontagne, Francois; Loeb, Mark; Marcucci, Maura; McLeod, Shelley L.; Motaghi, Sharhzad; Murthy, Srinivas; Mustafa, Reem A.; Neary, John D.; Pardo-Hernandez, Hector; Rada, Gabriel; Rochwerg, Bram; Switzer, Charlotte; Tendal, Britta; Thabane, Lehana; Vandvik, Per O.; Vernooij, Robin W. M.; Viteri-García, Andrés; Wang, Ying; Yao, Liang; Ye, Zhikang; Guyatt, Gordon H.; Brignardello-Petersen, Romina
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| Publisher |
BMJ
|
| Date Issued |
2021
|
| Description |
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 metaanalysis
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.
Co nclusions
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.
|
| Genre | |
| Type | |
| Language |
eng
|
| Date Available |
2021-06-17
|
| Provider |
Vancouver : University of British Columbia Library
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| Rights |
Attribution-NonCommercial 4.0 International
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| DOI |
10.14288/1.0398456
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| URI | |
| Affiliation | |
| Citation |
Bartoszko, J. J., Siemieniuk, R. A. C., Kum, E., Qasim, A., Zeraatkar, D., Ge, L., Han, M. A., Sadeghirad, B., Agarwal, A., Agoritsas, T., Chu, D. K., Couban, R., Darzi, A. J., Devji, T., Ghadimi, M., Honarmand, K., Izcovich, A., Khamis, A., Lamontagne, F., . . . Brignardello-Petersen, R. (2021). Prophylaxis against covid-19: Living systematic review and network meta-analysis. BMJ (Online), 373, n949-n949.
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| Publisher DOI |
10.1136/bmj.n949
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| Peer Review Status |
Reviewed
|
| Scholarly Level |
Faculty; Researcher; Postdoctoral; Graduate
|
| Copyright Holder |
Authors
|
| Rights URI | |
| Aggregated Source Repository |
DSpace
|
Item Media
Item Citations and Data
Rights
Attribution-NonCommercial 4.0 International