PURPOSE:

• Skipper et al. (Annals of Internal Medicine, 2020) sought to determine if hydroxychloroquine is of benefit to individuals with COVID-19 early in their clinical course  

METHODS:

• Multisite, international, randomized, double-blind, placebo-controlled trial (March 22 through May 20, with final hospital outcomes available June 15, 2020)  
  • 40 states (US) | 3 provinces (Canada)
  • Researchers collected self-reported survey data using the Research Electronic Data Capture (REDCap) system | Outreach traditional and through social media
• Participants
  • Nonhospitalized | ≤4 days of symptoms with
    • Laboratory-confirmed COVID-19 or COVID-19–compatible symptoms and in contact with COVID-19 positive individual
  • Symptomatic health care workers with high-risk exposure but whose contact had PCR results pending were also included
• Randomized 1:1 to the following
  • Oral hydroxychloroquine: 800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 more days
  • Masked placebo
• Measurements
  • Symptoms and severity at baseline and then at days 3, 5, 10, and 14
  • Assessed using a 10-point visual analogue scale
• Outcomes
  • The primary end point was changed to an overall symptom severity score over the course of 14 days

RESULTS:

• 423 contributed primary end point data (out of 491 randomized)
  • Median age: 40 years | 56% women | Identified as Black or African American were underrepresented (3%)  
  • Enrolled within 1 day of onset of symptoms: 56% (236 of 423)
• Change in symptom severity over 14 days did not differ between groups
  • Absolute difference in symptom severity: −0.27 points (95% CI, −0.61 to 0.07 points; P=0.117)
• There was no difference in proportion of patients with ongoing symptoms at 14 days (P=0.21)
  • Hydroxychloroquine: 24%
  • Placebo: 30%
• Medication adverse effects were more frequent with hydroxychloroquine (P < 0.001)
  • Hydroxychloroquine: 43%
  • Placebo: 22%
• There was no significant difference in hospitalization or death (P = 0.29)
  • Hydroxychloroquine: 4 hospitalizations occurred | 1 nonhospitalized death
  • Placebo: 10 hospitalizations (2 non–COVID-19–related) | 1 hospitalized death

CONCLUSION:

• The authors note that the population was relatively young, with few comorbid conditions and therefore these outcomes may not be generalizable to all population groups | A substantial proportion of patients were enrolled based on symptoms and not SARS-CoV-2 testing (due to limited availability)
• The authors conclude that

Hydroxychloroquine did not substantially reduce symptom severity in outpatients with early, mild COVID-19

Learn More – Primary Sources:

Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19