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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.
  • Bartoszko JJ; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
  • Siemieniuk RAC; Joint first authors.
  • Kum E; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada reed.siemieniuk@medportal.ca.
  • Qasim A; Joint first authors.
  • Zeraatkar D; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
  • Ge L; Joint first authors.
  • Han MA; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
  • Sadeghirad B; Joint first authors.
  • Agarwal A; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
  • Agoritsas T; Joint first authors.
  • Chu DK; Evidence Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, Gansu, China.
  • Couban R; Joint first authors.
  • Darzi AJ; Department of Preventive Medicine, College of Medicine, Chosun University, Gwangju, Republic of Korea.
  • Devji T; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
  • Ghadimi M; Department of Anesthesia, McMaster University, Hamilton, ON, Canada.
  • Honarmand K; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
  • Izcovich A; Department of Medicine, University of Toronto, Toronto, ON, Canada.
  • Khamis A; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
  • Lamontagne F; Division of General Internal Medicine & Division of Clinical Epidemiology, University Hospitals of Geneva, Geneva, Switzerland.
  • Loeb M; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
  • Marcucci M; Department of Medicine, McMaster University, Hamilton, ON, Canada.
  • McLeod SL; Department of Anesthesia, McMaster University, Hamilton, ON, Canada.
  • Motaghi S; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
  • Murthy S; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
  • Mustafa RA; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
  • Neary JD; Department of Medicine, Western University, London, ON, Canada.
  • Pardo-Hernandez H; Servicio de Clinica Médica del Hospital Alemán, Buenos Aires, Argentina.
  • Rada G; Wolfson Palliative Care Research Centre, Hull York Medical School, York, UK.
  • Rochwerg B; Department of Medicine and Centre de recherche du CHU de Sherbrooke, Sherbrooke, QC, Canada.
  • Switzer C; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
  • Tendal B; Department of Medicine, McMaster University, Hamilton, ON, Canada.
  • Thabane L; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
  • Vandvik PO; Department of Medicine, McMaster University, Hamilton, ON, Canada.
  • Vernooij RWM; Schwartz/Reisman Emergency Medicine Institute, Sinai Health, Toronto, ON, Canada.
  • Viteri-García A; Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada.
  • Wang Y; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
  • Yao L; Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
  • Ye Z; Department of Medicine, University of Kansas Medical Center, Kansas City, MO, USA.
  • Guyatt GH; Department of Medicine, McMaster University, Hamilton, ON, Canada.
  • Brignardello-Petersen R; Iberoamerican Cochrane Centre, Sant Pau Biomedical Research Institute (IIB Sant Pau), Barcelona, Spain.
BMJ ; 373: n949, 2021 04 26.
Article in English | MEDLINE | ID: covidwho-1203960
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Ivermectin / Carrageenan / Global Health / COVID-19 / Hydroxychloroquine Type of study: Experimental Studies / Prognostic study / Randomized controlled trials / Reviews / Systematic review/Meta Analysis Limits: Humans Language: English Journal: BMJ Journal subject: Medicine Year: 2021 Document Type: Article Affiliation country: Bmj.n949

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Ivermectin / Carrageenan / Global Health / COVID-19 / Hydroxychloroquine Type of study: Experimental Studies / Prognostic study / Randomized controlled trials / Reviews / Systematic review/Meta Analysis Limits: Humans Language: English Journal: BMJ Journal subject: Medicine Year: 2021 Document Type: Article Affiliation country: Bmj.n949