Evidence map›Paper›PMID 33068425›Full record

Trial reportClinical infectious diseases : an official publication of the Infectious Diseases Society of America2021

Hydroxychloroquine as Pre-exposure Prophylaxis for Coronavirus Disease 2019 (COVID-19) in Healthcare Workers: A Randomized Trial.

Radha Rajasingham, Ananta S Bangdiwala, Melanie R Nicol, Caleb P Skipper, Katelyn A Pastick, Margaret L Axelrod, Matthew F Pullen, Alanna A Nascene, Darlisha A Williams, Nicole W Engen and 13 more

Registry-linked trialOpen access · bronzeAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04328467 (Pre-exposure Prophylaxis for SARS-Coronavirus-2), which is not on this map. Cited by 80 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed, 11 pooled it
3.0field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04328467 phase3completednot on this map

Pre-exposure Prophylaxis for SARS-Coronavirus-2: A Pragmatic Randomized Clinical Trial

TypeinterventionalSponsorUniversity of MinnesotaRan2020 to 2020Enrolled1,483ConditionsCOVID-19, Corona Virus Infection, ARDS, Acute Respiratory Distress SyndromeArmsHydroxychloroquine, Placebo
3 · Its place in the literature

Who cites it

80 citing papers in PubMed, 11 syntheses or guidelines pooled it, 127 citations in OpenAlex.

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  6. Efficacy and safety of hydroxychloroquine/chloroquine against SARS-CoV-2 infection: A systematic review and meta-analysis.Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy · 2021
    Pooled it
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  9. Prophylaxis for COVID-19: a systematic review.Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2021
    Pooled it
  10. Use of hydroxychloroquine to prevent SARS-CoV-2 infection and treat mild COVID-19: a systematic review and meta-analysis.Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia · 2021
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  15. Daily tenofovir disoproxil fumarate/emtricitabine and hydroxychloroquine for pre-exposure prophylaxis of COVID-19: a double-blind placebo-controlled randomized trial in healthcare workers.Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2023
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20 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 5 institutions in 2 countries.

Radha RajasinghamUniversity of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0001-5531-0231
Ananta S BangdiwalaUniversity of Minnesota, Minneapolis, Minnesota, USA.
Melanie R NicolUniversity of Minnesota, Minneapolis, Minnesota, USA.
Caleb P SkipperUniversity of Minnesota, Minneapolis, Minnesota, USA.
Katelyn A PastickUniversity of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0002-1306-1713
Margaret L AxelrodVanderbilt University Medical Center, Nashville, Tennessee, USA.
Matthew F PullenUniversity of Minnesota, Minneapolis, Minnesota, USA.
Alanna A NasceneUniversity of Minnesota, Minneapolis, Minnesota, USA.
Darlisha A WilliamsUniversity of Minnesota, Minneapolis, Minnesota, USA.
Nicole W EngenUniversity of Minnesota, Minneapolis, Minnesota, USA.
Elizabeth C OkaforUniversity of Minnesota, Minneapolis, Minnesota, USA.
Brian I RiniVanderbilt University Medical Center, Nashville, Tennessee, USA.
Ingrid A MayerVanderbilt University Medical Center, Nashville, Tennessee, USA.
Emily G McDonaldResearch Institute of the McGill University Health Centre and the Clinical Practice Assessment Unit, Department of Medicine, McGill University, Montreal, Quebec, Canada.
Todd C LeeResearch Institute of the McGill University Health Centre and the Clinical Practice Assessment Unit, Department of Medicine, McGill University, Montreal, Quebec, Canada.
Peter LiOregon Health and Science University, Portland, Oregon, USA.
Lauren J MacKenzieSection of Infectious Diseases, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Justin M BalkoVanderbilt University Medical Center, Nashville, Tennessee, USA.
Stephen J DunlopUniversity of Minnesota, Minneapolis, Minnesota, USA.
Katherine H HullsiekUniversity of Minnesota, Minneapolis, Minnesota, USA.
David R BoulwareUniversity of Minnesota, Minneapolis, Minnesota, USA.
Sarah M LofgrenUniversity of Minnesota, Minneapolis, Minnesota, USA.
COVID PREP team
University of Minnesota · USVanderbilt University Medical Center · USMcGill University Health Centre · CAOregon Health & Science University · USUniversity of Manitoba · CA

Funding

University of Minnesota Clinical and Translational Science Institute (UMN CTSI)UL1TR002494 · NCATS · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R, WEISDORF, DANIEL J · 2018 to 2022
$34.9M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007347 · NIGMS · VANDERBILT UNIVERSITY · PI WILLIAMS, CHRISTOPHER S. · 1985 to 2023
$26.3M
NPGH LEADERs YR12: OBSSR (Greenberg, Ngwafong Mukere) & NIBIB (Lee)D43TW009345 · FIC · UNIVERSITY OF WASHINGTON · PI Dibyadyuti Datta, Chandy C. John · 2017 to 2026
$15.2M
Improving Diagnostics and Neurocognitive Outcomes in HIV/AIDS-related MeningitisR01NS086312 · NINDS · UNIVERSITY OF MINNESOTA · PI David R Boulware, David Bisagaya Meya · 2013 to 2026
$8.3M
Infectious Disease Training in Clinical InvestigationT32AI055433 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI David R Boulware · 2003 to 2026
$6.1M
Medical Scientist Training ProgramT32GM152284 · NIGMS · VANDERBILT UNIVERSITY · PI Christopher S. Williams · 2024 to 2026
$4.8M
Operational Research for Cryptococcal Antigen Screening (ORCAS) of HIV PatientsU01AI125003 · NIAID · UNIVERSITY OF MINNESOTA · PI BOULWARE, DAVID R, MEYA, DAVID BISAGAYA · 2016 to 2020
$3.4M
Evaluation of CRAG screening with enhanced antifungal therapy for asymptomatic CRAG-positive personsK23AI138851 · NIAID · UNIVERSITY OF MINNESOTA · PI RAJASINGHAM, RADHA · 2018 to 2022
$954k
Evaluating Antiretroviral Pharmacology in the Female Genital Tract to Optimize HIV PreventionK08AI134262 · NIAID · UNIVERSITY OF MINNESOTA · PI NICOL, MELANIE RAE · 2018 to 2022
$847k
Neuroinflammation and Modulating Factors in Depression and HIVK23MH121220 · NIMH · UNIVERSITY OF MINNESOTA · PI LOFGREN, SARAH · 2019 to 2022
$795k
Medical Student Summer Research Program in Infection and ImmunityT35AI118620 · NIAID · UNIVERSITY OF MINNESOTA · PI MUELLER, DANIEL L · 2015 to 2025
$351k
Modulation of the anti-tumor immune response by Major Histocompatibility Class-II expression on tumor cellsF30CA236157 · NCI · VANDERBILT UNIVERSITY · PI AXELROD, MARGARET · 2019 to 2021
$133k
FIC NIH HHS D43 TW009345FIC NIH HHS L30 TW011500NCATS NIH HHS UL1 TR002494NCI NIH HHS F30 CA236157NIAID NIH HHS K08 AI134262NIAID NIH HHS K23 AI138851NIAID NIH HHS T32 AI055433NIAID NIH HHS T35 AI118620NIGMS NIH HHS T32 GM007347NIGMS NIH HHS T32 GM152284NIMH NIH HHS K23 MH121220NINDS NIH HHS R01 NS086312
6 · The paper itself

Abstract

backgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging virus causing the ongoing coronavirus disease 2019 (COVID-19) pandemic with no known effective prophylaxis. We investigated whether hydroxychloroquine could prevent SARS-CoV-2 in healthcare workers at high risk of exposure.

methodsWe conducted a randomized, double-blind, placebo-controlled clinical trial of healthcare workers with ongoing exposure to persons with SARS-CoV-2, including those working in emergency departments, intensive care units, COVID-19 hospital wards, and first responders. Participants across the United States and in the Canadian province of Manitoba were randomized to hydroxychloroquine loading dose then 400 mg once or twice weekly for 12 weeks. The primary endpoint was confirmed or probable COVID-19-compatible illness. We measured hydroxychloroquine whole-blood concentrations.

resultsWe enrolled 1483 healthcare workers, of whom 79% reported performing aerosol-generating procedures. The incidence of COVID-19 (laboratory-confirmed or symptomatic compatible illness) was 0.27 events/person-year with once-weekly and 0.28 events/person-year with twice-weekly hydroxychloroquine compared with 0.38 events/person-year with placebo. For once-weekly hydroxychloroquine prophylaxis, the hazard ratio was .72 (95% CI, .44-1.16; P = .18) and for twice-weekly was .74 (95% CI, .46-1.19; P = .22) compared with placebo. Median hydroxychloroquine concentrations in whole blood were 98 ng/mL (IQR, 82-120) with once-weekly and 200 ng/mL (IQR, 159-258) with twice-weekly dosing. Hydroxychloroquine concentrations did not differ between participants who developed COVID-19-compatible illness (154 ng/mL) versus participants without COVID-19 (133 ng/mL; P = .08).

conclusionsPre-exposure prophylaxis with hydroxychloroquine once or twice weekly did not significantly reduce laboratory-confirmed COVID-19 or COVID-19-compatible illness among healthcare workers. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov NCT04328467.

Indexed as

COVID-19 Drug TreatmentPre-Exposure ProphylaxisCanadaHealth PersonnelHumansHydroxychloroquineSARS-CoV-2HydroxychloroquineCOVID-19healthcare workershydroxychloroquinepre-exposure prophylaxis

Identifiers

PMID33068425
PMCPMC7665393
OpenAlexW3092981332

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.