• Caleb P Skipper, Katelyn A Pastick, Nicole W Engen, Ananta S Bangdiwala, Mahsa Abassi, Sarah M Lofgren, Darlisha A Williams, Elizabeth C Okafor, Matthew F Pullen, Melanie R Nicol, Alanna A Nascene, Kathy H Hullsiek, Matthew P Cheng, Darlette Luke, Sylvain A Lother, Lauren J MacKenzie, Glen Drobot, Lauren E Kelly, Ilan S Schwartz, Ryan Zarychanski, Emily G McDonald, Todd C Lee, Radha Rajasingham, and David R Boulware.
• University of Minnesota, Minneapolis, Minnesota (C.P.S., K.A.P., N.W.E., A.S.B., M.A., S.M.L., D.A.W., E.C.O., M.F.P., M.R.N., A.A.N., K.H.H., R.R., D.R.B.).
• Ann. Intern. Med. 2020 Oct 20; 173 (8): 623631623-631.

BackgroundNo effective oral therapy exists for early coronavirus disease 2019 (COVID-19).ObjectiveTo investigate whether hydroxychloroquine could reduce COVID-19 severity in adult outpatients.DesignRandomized, double-blind, placebo-controlled trial conducted from 22 March through 20 May 2020. (ClinicalTrials.gov: NCT04308668).SettingInternet-based trial across the United States and Canada (40 states and 3 provinces).ParticipantsSymptomatic, nonhospitalized adults with laboratory-confirmed COVID-19 or probable COVID-19 and high-risk exposure within 4 days of symptom onset.InterventionOral hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 more days) or masked placebo.MeasurementsSymptoms and severity at baseline and then at days 3, 5, 10, and 14 using a 10-point visual analogue scale. The primary end point was change in overall symptom severity over 14 days.ResultsOf 491 patients randomly assigned to a group, 423 contributed primary end point data. Of these, 341 (81%) had laboratory-confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or epidemiologically linked exposure to a person with laboratory-confirmed infection; 56% (236 of 423) were enrolled within 1 day of symptoms starting. Change in symptom severity over 14 days did not differ between the hydroxychloroquine and placebo groups (difference in symptom severity: relative, 12%; absolute, -0.27 point [95% CI, -0.61 to 0.07 point]; P = 0.117). At 14 days, 24% (49 of 201) of participants receiving hydroxychloroquine had ongoing symptoms compared with 30% (59 of 194) receiving placebo (P = 0.21). Medication adverse effects occurred in 43% (92 of 212) of participants receiving hydroxychloroquine versus 22% (46 of 211) receiving placebo (P < 0.001). With placebo, 10 hospitalizations occurred (2 non-COVID-19-related), including 1 hospitalized death. With hydroxychloroquine, 4 hospitalizations occurred plus 1 nonhospitalized death (P = 0.29).LimitationOnly 58% of participants received SARS-CoV-2 testing because of severe U.S. testing shortages.ConclusionHydroxychloroquine did not substantially reduce symptom severity in outpatients with early, mild COVID-19.Primary Funding SourcePrivate donors.

26 keywords...

hide…