Ann Intern Med . Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19: A Randomized Trial

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Ann Intern Med


. 2020 Jul 16.
doi: 10.7326/M20-4207. Online ahead of print.
Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19: A Randomized Trial


Caleb P Skipper ¹ , Katelyn A Pastick ¹ , Nicole W Engen ¹ , Ananta S Bangdiwala ¹ , Mahsa Abassi ¹ , Sarah M Lofgren ¹ , Darlisha A Williams ¹ , Elizabeth C Okafor ¹ , Matthew F Pullen ¹ , Melanie R Nicol ¹ , Alanna A Nascene ¹ , Kathy H Hullsiek ¹ , Matthew P Cheng ² , Darlette Luke ³ , Sylvain A Lother ⁴ , Lauren J MacKenzie ⁴ , Glen Drobot ⁴ , Lauren E Kelly ⁵ , Ilan S Schwartz ⁶ , Ryan Zarychanski ⁴ , Emily G McDonald ² , Todd C Lee ² , Radha Rajasingham ¹ , David R Boulware ¹



Affiliations

• PMID: 32673060
• DOI: 10.7326/M20-4207

Abstract

Background: No effective oral therapy exists for early coronavirus disease 2019 (COVID-19).
Objective: To investigate whether hydroxychloroquine could reduce COVID-19 severity in adult outpatients.
Design: Randomized, double-blind, placebo-controlled trial conducted from 22 March through 20 May 2020. (ClinicalTrials.gov: NCT04308668).
Setting: Internet-based trial across the United States and Canada (40 states and 3 provinces).
Participants: Symptomatic, nonhospitalized adults with laboratory-confirmed COVID-19 or probable COVID-19 and high-risk exposure within 4 days of symptom onset.
Intervention: Oral hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 more days) or masked placebo. Measures: Symptoms 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.
Results: Of 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 points [95% CI, -0.61 to 0.07 points]; 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).
Limitations: Only 58% of participants received SARS-CoV-2 testing because of severe U.S. testing shortages.
Conclusion: Hydroxychloroquine did not substantially reduce symptom severity in outpatients with early, mild COVID-19.
Primary funding source: Private donors.