Safety of Hydroxychloroquine Among Outpatient Clinical Trial Participants for COVID-19.
Identifieur interne : 000808 ( Main/Corpus ); précédent : 000807; suivant : 000809Safety of Hydroxychloroquine Among Outpatient Clinical Trial Participants for COVID-19.
Auteurs : Sarah M. Lofgren ; Melanie R. Nicol ; Ananta S. Bangdiwala ; Katelyn A. Pastick ; Elizabeth C. Okafor ; Caleb P. Skipper ; Matthew F. Pullen ; Nicole W. Engen ; Mahsa Abassi ; Darlisha A. Williams ; Alanna A. Nascene ; Margaret L. Axelrod ; Sylvain A. Lother ; Lauren J. Mackenzie ; Glen Drobot ; Nicole Marten ; Matthew P. Cheng ; Ryan Zarychanski ; Ilan S. Schwartz ; Michael Silverman ; Zain Chagla ; Lauren E. Kelly ; Emily G. Mcdonald ; Todd C. Lee ; Kathy H. Hullsiek ; David R. Boulware ; Radha RajasinghamSource :
- Open forum infectious diseases [ 2328-8957 ] ; 2020.
Abstract
Background
Use of hydroxychloroquine in hospitalized patients with coronavirus disease 2019 (COVID-19), especially in combination with azithromycin, has raised safety concerns. Here, we report safety data from 3 outpatient randomized clinical trials.
Methods
We conducted 3 randomized, double-blind, placebo-controlled trials investigating hydroxychloroquine as pre-exposure prophylaxis, postexposure prophylaxis, and early treatment for COVID-19 using an internet-based design. We excluded individuals with contraindications to hydroxychloroquine. We collected side effects and serious adverse events. We report descriptive analyses of our findings.
Results
We enrolled 2795 participants. The median age of research participants (interquartile range) was 40 (34-49) years, and 59% (1633/2767) reported no chronic medical conditions. Overall 2544 (91%) participants reported side effect data, and 748 (29%) reported at least 1 medication side effect. Side effects were reported in 40% with once-daily, 36% with twice-weekly, 31% with once-weekly hydroxychloroquine, compared with 19% with placebo. The most common side effects were upset stomach or nausea (25% with once-daily, 19% with twice-weekly, and 18% with once-weekly hydroxychloroquine, vs 11% for placebo), followed by diarrhea, vomiting, or abdominal pain (23% for once-daily, 17% twice-weekly, and 13% once-weekly hydroxychloroquine, vs 7% for placebo). Two individuals were hospitalized for atrial arrhythmias, 1 on placebo and 1 on twice-weekly hydroxychloroquine. No sudden deaths occurred.
Conclusions
Data from 3 outpatient COVID-19 trials demonstrated that gastrointestinal side effects were common but mild with the use of hydroxychloroquine, while serious side effects were rare. No deaths occurred related to hydroxychloroquine. Randomized clinical trials, in cohorts of healthy outpatients, can safely investigate whether hydroxychloroquine is efficacious for COVID-19.
ClinicalTrialsgov Identifier
NCT04308668 for postexposure prophylaxis and early treatment trials; NCT04328467 for pre-exposure prophylaxis trial.
DOI: 10.1093/ofid/ofaa500
PubMed: 33204764
PubMed Central: PMC7654376
Links to Exploration step
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Bangdiwala</name><affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Pastick, Katelyn A" sort="Pastick, Katelyn A" uniqKey="Pastick K" first="Katelyn A" last="Pastick">Katelyn A. Pastick</name><affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Okafor, Elizabeth C" sort="Okafor, Elizabeth C" uniqKey="Okafor E" first="Elizabeth C" last="Okafor">Elizabeth C. Okafor</name><affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Skipper, Caleb P" sort="Skipper, Caleb P" uniqKey="Skipper C" first="Caleb P" last="Skipper">Caleb P. 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Nascene</name><affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Axelrod, Margaret L" sort="Axelrod, Margaret L" uniqKey="Axelrod M" first="Margaret L" last="Axelrod">Margaret L. Axelrod</name><affiliation><nlm:affiliation>Vanderbilt University Medical Center, Nashville, Tennessee, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Lother, Sylvain A" sort="Lother, Sylvain A" uniqKey="Lother S" first="Sylvain A" last="Lother">Sylvain A. Lother</name><affiliation><nlm:affiliation>Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Mackenzie, Lauren J" sort="Mackenzie, Lauren J" uniqKey="Mackenzie L" first="Lauren J" last="Mackenzie">Lauren J. Mackenzie</name><affiliation><nlm:affiliation>Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Drobot, Glen" sort="Drobot, Glen" uniqKey="Drobot G" first="Glen" last="Drobot">Glen Drobot</name><affiliation><nlm:affiliation>Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Marten, Nicole" sort="Marten, Nicole" uniqKey="Marten N" first="Nicole" last="Marten">Nicole Marten</name><affiliation><nlm:affiliation>George & Fay Yee Centre for Healthcare Innovation, Winnipeg, Manitoba, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Cheng, Matthew P" sort="Cheng, Matthew P" uniqKey="Cheng M" first="Matthew P" last="Cheng">Matthew P. Cheng</name><affiliation><nlm:affiliation>Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Clinical Practice Assessment Unit, Department of Medicine, McGill University, Montreal, Quebec, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Zarychanski, Ryan" sort="Zarychanski, Ryan" uniqKey="Zarychanski R" first="Ryan" last="Zarychanski">Ryan Zarychanski</name><affiliation><nlm:affiliation>Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>George & Fay Yee Centre for Healthcare Innovation, Winnipeg, Manitoba, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Schwartz, Ilan S" sort="Schwartz, Ilan S" uniqKey="Schwartz I" first="Ilan S" last="Schwartz">Ilan S. Schwartz</name><affiliation><nlm:affiliation>Division of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Silverman, Michael" sort="Silverman, Michael" uniqKey="Silverman M" first="Michael" last="Silverman">Michael Silverman</name><affiliation><nlm:affiliation>Lawson Research Institute, St. Joseph's Healthcare Center, London, Ontario.</nlm:affiliation></affiliation></author><author><name sortKey="Chagla, Zain" sort="Chagla, Zain" uniqKey="Chagla Z" first="Zain" last="Chagla">Zain Chagla</name><affiliation><nlm:affiliation>McMaster University, Hamilton, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Kelly, Lauren E" sort="Kelly, Lauren E" uniqKey="Kelly L" first="Lauren E" last="Kelly">Lauren E. Kelly</name><affiliation><nlm:affiliation>George & Fay Yee Centre for Healthcare Innovation, Winnipeg, Manitoba, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Mcdonald, Emily G" sort="Mcdonald, Emily G" uniqKey="Mcdonald E" first="Emily G" last="Mcdonald">Emily G. Mcdonald</name><affiliation><nlm:affiliation>Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Clinical Practice Assessment Unit, Department of Medicine, McGill University, Montreal, Quebec, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Lee, Todd C" sort="Lee, Todd C" uniqKey="Lee T" first="Todd C" last="Lee">Todd C. Lee</name><affiliation><nlm:affiliation>Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Clinical Practice Assessment Unit, Department of Medicine, McGill University, Montreal, Quebec, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Hullsiek, Kathy H" sort="Hullsiek, Kathy H" uniqKey="Hullsiek K" first="Kathy H" last="Hullsiek">Kathy H. Hullsiek</name><affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Boulware, David R" sort="Boulware, David R" uniqKey="Boulware D" first="David R" last="Boulware">David R. Boulware</name><affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Rajasingham, Radha" sort="Rajasingham, Radha" uniqKey="Rajasingham R" first="Radha" last="Rajasingham">Radha Rajasingham</name><affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:33204764</idno><idno type="pmid">33204764</idno><idno type="doi">10.1093/ofid/ofaa500</idno><idno type="pmc">PMC7654376</idno><idno type="wicri:Area/Main/Corpus">000808</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000808</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Safety of Hydroxychloroquine Among Outpatient Clinical Trial Participants for COVID-19.</title><author><name sortKey="Lofgren, Sarah M" sort="Lofgren, Sarah M" uniqKey="Lofgren S" first="Sarah M" last="Lofgren">Sarah M. Lofgren</name><affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Nicol, Melanie R" sort="Nicol, Melanie R" uniqKey="Nicol M" first="Melanie R" last="Nicol">Melanie R. Nicol</name><affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Bangdiwala, Ananta S" sort="Bangdiwala, Ananta S" uniqKey="Bangdiwala A" first="Ananta S" last="Bangdiwala">Ananta S. Bangdiwala</name><affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Pastick, Katelyn A" sort="Pastick, Katelyn A" uniqKey="Pastick K" first="Katelyn A" last="Pastick">Katelyn A. Pastick</name><affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Okafor, Elizabeth C" sort="Okafor, Elizabeth C" uniqKey="Okafor E" first="Elizabeth C" last="Okafor">Elizabeth C. Okafor</name><affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Skipper, Caleb P" sort="Skipper, Caleb P" uniqKey="Skipper C" first="Caleb P" last="Skipper">Caleb P. Skipper</name><affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Pullen, Matthew F" sort="Pullen, Matthew F" uniqKey="Pullen M" first="Matthew F" last="Pullen">Matthew F. Pullen</name><affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Engen, Nicole W" sort="Engen, Nicole W" uniqKey="Engen N" first="Nicole W" last="Engen">Nicole W. Engen</name><affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Abassi, Mahsa" sort="Abassi, Mahsa" uniqKey="Abassi M" first="Mahsa" last="Abassi">Mahsa Abassi</name><affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Williams, Darlisha A" sort="Williams, Darlisha A" uniqKey="Williams D" first="Darlisha A" last="Williams">Darlisha A. Williams</name><affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Nascene, Alanna A" sort="Nascene, Alanna A" uniqKey="Nascene A" first="Alanna A" last="Nascene">Alanna A. Nascene</name><affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Axelrod, Margaret L" sort="Axelrod, Margaret L" uniqKey="Axelrod M" first="Margaret L" last="Axelrod">Margaret L. Axelrod</name><affiliation><nlm:affiliation>Vanderbilt University Medical Center, Nashville, Tennessee, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Lother, Sylvain A" sort="Lother, Sylvain A" uniqKey="Lother S" first="Sylvain A" last="Lother">Sylvain A. Lother</name><affiliation><nlm:affiliation>Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Mackenzie, Lauren J" sort="Mackenzie, Lauren J" uniqKey="Mackenzie L" first="Lauren J" last="Mackenzie">Lauren J. Mackenzie</name><affiliation><nlm:affiliation>Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Drobot, Glen" sort="Drobot, Glen" uniqKey="Drobot G" first="Glen" last="Drobot">Glen Drobot</name><affiliation><nlm:affiliation>Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Marten, Nicole" sort="Marten, Nicole" uniqKey="Marten N" first="Nicole" last="Marten">Nicole Marten</name><affiliation><nlm:affiliation>George & Fay Yee Centre for Healthcare Innovation, Winnipeg, Manitoba, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Cheng, Matthew P" sort="Cheng, Matthew P" uniqKey="Cheng M" first="Matthew P" last="Cheng">Matthew P. Cheng</name><affiliation><nlm:affiliation>Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Clinical Practice Assessment Unit, Department of Medicine, McGill University, Montreal, Quebec, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Zarychanski, Ryan" sort="Zarychanski, Ryan" uniqKey="Zarychanski R" first="Ryan" last="Zarychanski">Ryan Zarychanski</name><affiliation><nlm:affiliation>Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>George & Fay Yee Centre for Healthcare Innovation, Winnipeg, Manitoba, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Schwartz, Ilan S" sort="Schwartz, Ilan S" uniqKey="Schwartz I" first="Ilan S" last="Schwartz">Ilan S. Schwartz</name><affiliation><nlm:affiliation>Division of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Silverman, Michael" sort="Silverman, Michael" uniqKey="Silverman M" first="Michael" last="Silverman">Michael Silverman</name><affiliation><nlm:affiliation>Lawson Research Institute, St. Joseph's Healthcare Center, London, Ontario.</nlm:affiliation></affiliation></author><author><name sortKey="Chagla, Zain" sort="Chagla, Zain" uniqKey="Chagla Z" first="Zain" last="Chagla">Zain Chagla</name><affiliation><nlm:affiliation>McMaster University, Hamilton, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Kelly, Lauren E" sort="Kelly, Lauren E" uniqKey="Kelly L" first="Lauren E" last="Kelly">Lauren E. Kelly</name><affiliation><nlm:affiliation>George & Fay Yee Centre for Healthcare Innovation, Winnipeg, Manitoba, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Mcdonald, Emily G" sort="Mcdonald, Emily G" uniqKey="Mcdonald E" first="Emily G" last="Mcdonald">Emily G. Mcdonald</name><affiliation><nlm:affiliation>Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Clinical Practice Assessment Unit, Department of Medicine, McGill University, Montreal, Quebec, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Lee, Todd C" sort="Lee, Todd C" uniqKey="Lee T" first="Todd C" last="Lee">Todd C. Lee</name><affiliation><nlm:affiliation>Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Clinical Practice Assessment Unit, Department of Medicine, McGill University, Montreal, Quebec, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Hullsiek, Kathy H" sort="Hullsiek, Kathy H" uniqKey="Hullsiek K" first="Kathy H" last="Hullsiek">Kathy H. Hullsiek</name><affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Boulware, David R" sort="Boulware, David R" uniqKey="Boulware D" first="David R" last="Boulware">David R. Boulware</name><affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Rajasingham, Radha" sort="Rajasingham, Radha" uniqKey="Rajasingham R" first="Radha" last="Rajasingham">Radha Rajasingham</name><affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Open forum infectious diseases</title><idno type="ISSN">2328-8957</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>Background</b></p><p>Use of hydroxychloroquine in hospitalized patients with coronavirus disease 2019 (COVID-19), especially in combination with azithromycin, has raised safety concerns. Here, we report safety data from 3 outpatient randomized clinical trials.</p></div><div type="abstract" xml:lang="en"><p><b>Methods</b></p><p>We conducted 3 randomized, double-blind, placebo-controlled trials investigating hydroxychloroquine as pre-exposure prophylaxis, postexposure prophylaxis, and early treatment for COVID-19 using an internet-based design. We excluded individuals with contraindications to hydroxychloroquine. We collected side effects and serious adverse events. We report descriptive analyses of our findings.</p></div><div type="abstract" xml:lang="en"><p><b>Results</b></p><p>We enrolled 2795 participants. The median age of research participants (interquartile range) was 40 (34-49) years, and 59% (1633/2767) reported no chronic medical conditions. Overall 2544 (91%) participants reported side effect data, and 748 (29%) reported at least 1 medication side effect. Side effects were reported in 40% with once-daily, 36% with twice-weekly, 31% with once-weekly hydroxychloroquine, compared with 19% with placebo. The most common side effects were upset stomach or nausea (25% with once-daily, 19% with twice-weekly, and 18% with once-weekly hydroxychloroquine, vs 11% for placebo), followed by diarrhea, vomiting, or abdominal pain (23% for once-daily, 17% twice-weekly, and 13% once-weekly hydroxychloroquine, vs 7% for placebo). Two individuals were hospitalized for atrial arrhythmias, 1 on placebo and 1 on twice-weekly hydroxychloroquine. No sudden deaths occurred.</p></div><div type="abstract" xml:lang="en"><p><b>Conclusions</b></p><p>Data from 3 outpatient COVID-19 trials demonstrated that gastrointestinal side effects were common but mild with the use of hydroxychloroquine, while serious side effects were rare. No deaths occurred related to hydroxychloroquine. Randomized clinical trials, in cohorts of healthy outpatients, can safely investigate whether hydroxychloroquine is efficacious for COVID-19.</p></div><div type="abstract" xml:lang="en"><p><b>ClinicalTrialsgov Identifier</b></p><p>NCT04308668 for postexposure prophylaxis and early treatment trials; NCT04328467 for pre-exposure prophylaxis trial.</p></div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">33204764</PMID><DateRevised><Year>2021</Year><Month>04</Month><Day>28</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Print">2328-8957</ISSN><JournalIssue CitedMedium="Print"><Volume>7</Volume><Issue>11</Issue><PubDate><Year>2020</Year><Month>Nov</Month></PubDate></JournalIssue><Title>Open forum infectious diseases</Title><ISOAbbreviation>Open Forum Infect Dis</ISOAbbreviation></Journal><ArticleTitle>Safety of Hydroxychloroquine Among Outpatient Clinical Trial Participants for COVID-19.</ArticleTitle><Pagination><MedlinePgn>ofaa500</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1093/ofid/ofaa500</ELocationID><Abstract><AbstractText Label="Background" NlmCategory="UNASSIGNED">Use of hydroxychloroquine in hospitalized patients with coronavirus disease 2019 (COVID-19), especially in combination with azithromycin, has raised safety concerns. Here, we report safety data from 3 outpatient randomized clinical trials.</AbstractText><AbstractText Label="Methods" NlmCategory="UNASSIGNED">We conducted 3 randomized, double-blind, placebo-controlled trials investigating hydroxychloroquine as pre-exposure prophylaxis, postexposure prophylaxis, and early treatment for COVID-19 using an internet-based design. We excluded individuals with contraindications to hydroxychloroquine. We collected side effects and serious adverse events. We report descriptive analyses of our findings.</AbstractText><AbstractText Label="Results" NlmCategory="UNASSIGNED">We enrolled 2795 participants. The median age of research participants (interquartile range) was 40 (34-49) years, and 59% (1633/2767) reported no chronic medical conditions. Overall 2544 (91%) participants reported side effect data, and 748 (29%) reported at least 1 medication side effect. Side effects were reported in 40% with once-daily, 36% with twice-weekly, 31% with once-weekly hydroxychloroquine, compared with 19% with placebo. The most common side effects were upset stomach or nausea (25% with once-daily, 19% with twice-weekly, and 18% with once-weekly hydroxychloroquine, vs 11% for placebo), followed by diarrhea, vomiting, or abdominal pain (23% for once-daily, 17% twice-weekly, and 13% once-weekly hydroxychloroquine, vs 7% for placebo). Two individuals were hospitalized for atrial arrhythmias, 1 on placebo and 1 on twice-weekly hydroxychloroquine. No sudden deaths occurred.</AbstractText><AbstractText Label="Conclusions" NlmCategory="UNASSIGNED">Data from 3 outpatient COVID-19 trials demonstrated that gastrointestinal side effects were common but mild with the use of hydroxychloroquine, while serious side effects were rare. No deaths occurred related to hydroxychloroquine. Randomized clinical trials, in cohorts of healthy outpatients, can safely investigate whether hydroxychloroquine is efficacious for COVID-19.</AbstractText><AbstractText Label="ClinicalTrialsgov Identifier" NlmCategory="UNASSIGNED">NCT04308668 for postexposure prophylaxis and early treatment trials; NCT04328467 for pre-exposure prophylaxis trial.</AbstractText><CopyrightInformation>© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Lofgren</LastName><ForeName>Sarah M</ForeName><Initials>SM</Initials><Identifier Source="ORCID">0000-0001-6717-2614</Identifier><AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nicol</LastName><ForeName>Melanie R</ForeName><Initials>MR</Initials><AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bangdiwala</LastName><ForeName>Ananta S</ForeName><Initials>AS</Initials><AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pastick</LastName><ForeName>Katelyn A</ForeName><Initials>KA</Initials><Identifier Source="ORCID">0000-0002-1306-1713</Identifier><AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Okafor</LastName><ForeName>Elizabeth C</ForeName><Initials>EC</Initials><AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Skipper</LastName><ForeName>Caleb P</ForeName><Initials>CP</Initials><AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pullen</LastName><ForeName>Matthew F</ForeName><Initials>MF</Initials><AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Engen</LastName><ForeName>Nicole W</ForeName><Initials>NW</Initials><AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Abassi</LastName><ForeName>Mahsa</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Williams</LastName><ForeName>Darlisha A</ForeName><Initials>DA</Initials><AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nascene</LastName><ForeName>Alanna A</ForeName><Initials>AA</Initials><AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Axelrod</LastName><ForeName>Margaret L</ForeName><Initials>ML</Initials><AffiliationInfo><Affiliation>Vanderbilt University Medical Center, Nashville, Tennessee, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lother</LastName><ForeName>Sylvain A</ForeName><Initials>SA</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>MacKenzie</LastName><ForeName>Lauren J</ForeName><Initials>LJ</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Drobot</LastName><ForeName>Glen</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Marten</LastName><ForeName>Nicole</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>George & Fay Yee Centre for Healthcare Innovation, Winnipeg, Manitoba, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cheng</LastName><ForeName>Matthew P</ForeName><Initials>MP</Initials><AffiliationInfo><Affiliation>Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Clinical Practice Assessment Unit, Department of Medicine, McGill University, Montreal, Quebec, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zarychanski</LastName><ForeName>Ryan</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>George & Fay Yee Centre for Healthcare Innovation, Winnipeg, Manitoba, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schwartz</LastName><ForeName>Ilan S</ForeName><Initials>IS</Initials><AffiliationInfo><Affiliation>Division of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Silverman</LastName><ForeName>Michael</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Lawson Research Institute, St. Joseph's Healthcare Center, London, Ontario.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chagla</LastName><ForeName>Zain</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>McMaster University, Hamilton, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kelly</LastName><ForeName>Lauren E</ForeName><Initials>LE</Initials><AffiliationInfo><Affiliation>George & Fay Yee Centre for Healthcare Innovation, Winnipeg, Manitoba, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McDonald</LastName><ForeName>Emily G</ForeName><Initials>EG</Initials><AffiliationInfo><Affiliation>Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Clinical Practice Assessment Unit, Department of Medicine, McGill University, Montreal, Quebec, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lee</LastName><ForeName>Todd C</ForeName><Initials>TC</Initials><AffiliationInfo><Affiliation>Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Clinical Practice Assessment Unit, Department of Medicine, McGill University, Montreal, Quebec, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hullsiek</LastName><ForeName>Kathy H</ForeName><Initials>KH</Initials><AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Boulware</LastName><ForeName>David R</ForeName><Initials>DR</Initials><AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rajasingham</LastName><ForeName>Radha</ForeName><Initials>R</Initials><Identifier Source="ORCID">0000-0001-5531-0231</Identifier><AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><DataBankList CompleteYN="Y"><DataBank><DataBankName>ClinicalTrials.gov</DataBankName><AccessionNumberList><AccessionNumber>NCT04328467</AccessionNumber></AccessionNumberList></DataBank></DataBankList><GrantList CompleteYN="Y"><Grant><GrantID>R01 NS110519</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 NS086312</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>UL1 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