Safety of Hydroxychloroquine among Outpatient Clinical Trial Participants for COVID-19
Lofgren et al.
, Safety of Hydroxychloroquine among Outpatient Clinical Trial Participants for COVID-19
, Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa500 (date from earlier preprint)
Analysis of 2,795 outpatients not showing significant safety concerns with HCQ. No deaths were related to HCQ. There was one serious event requiring hospitalization, identical to the frequency with placebo.
Lofgren et al., 21 Sep 2020, peer-reviewed, 26 authors.
Abstract: Open Forum Infectious Diseases
Safety of Hydroxychloroquine Among Outpatient Clinical
Trial Participants for COVID-19
Sarah M. Lofgren,1, Melanie R. Nicol,1 Ananta S. Bangdiwala,1 Katelyn A. Pastick,1, Elizabeth C. Okafor,1 Caleb P. Skipper,1 Matthew F. Pullen,1
Nicole W. Engen,1 Mahsa Abassi,1 Darlisha A. Williams,1 Alanna A. Nascene,1 Margaret L. Axelrod,2 Sylvain A. Lother,3 Lauren J. MacKenzie,3
Glen Drobot,3 Nicole Marten4, Matthew P. Cheng,6,7 Ryan Zarychanski,3,4 Ilan S. Schwartz,5 Michael Silverman,8 Zain Chagla,9 Lauren E. Kelly,4
Emily G. McDonald,6,7 Todd C. Lee,6,7 Kathy H Hullsiek,1 David R. Boulware,1 and Radha Rajasingham1,
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 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.
NCT04308668 for postexposure prophylaxis and early treatment trials; NCT04328467 for preexposure prophylaxis trial.
COVID-19; hydroxychloroquine; safety; SARS-Cov2; side effects.
Hydroxychloroquine has in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
[1, 2]. While in vitro data suggest that both chloroquine and
hydroxychloroquine have activity against SARS-CoV-2 replication, the latter is generally considered less toxic and better
tolerated. However, clinical data to date demonstrate no conclusive efficacy of hydroxychloroquine for the treatment or prevention of coronavirus disease 2019 (COVID-19) [3–5]. Both
Received 17 July 2020; editorial decision 13 October 2020; accepted 15 October 2020.
Correspondence: Sarah Lofgren, MD, 689 23rd Avenue S.E., Minneapolis, MN..
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