Safety of Hydroxychloroquine Among Outpatient Clinical Trial Participants for COVID-19
MD 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 Rajasingham
Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa500
Background. Use of hydroxychloroquine in hospitalized patients with coronavirus disease 2019 , 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 preexposure 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 oncedaily, 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. ClinicalTrials.gov identifier. NCT04308668 for postexposure prophylaxis and early treatment trials; NCT04328467 for preexposure prophylaxis trial.
Supplementary Data Supplementary materials are available at Open Forum Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.
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' <jats:title>Background</jats:title>\n'
' <jats: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.</jats:p>\n'
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' <jats:sec>\n'
' <jats:title>Methods</jats:title>\n'
' <jats: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 '
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'events. We report descriptive analyses of our findings.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Results</jats:title>\n'
' <jats:p>We enrolled 2795 participants. The median age of research '
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'chronic medical conditions. Overall 2544 (91%) participants reported side effect data, and '
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'occurred.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Conclusions</jats:title>\n'
' <jats:p>Data from 3 outpatient COVID-19 trials demonstrated that '
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'serious side effects were rare. No deaths occurred related to hydroxychloroquine. Randomized '
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' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>ClinicalTrials.gov Identifier</jats:title>\n'
' <jats:p>NCT04308668 for postexposure prophylaxis and early treatment '
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