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Pharmacoepidemiology, Machine Learning and COVID-19: An intent-to-treat analysis of hydroxychloroquine, with or without azithromycin, and COVID-19 outcomes amongst hospitalized US Veterans

Journal Article · · American Journal of Epidemiology
DOI:https://doi.org/10.1093/aje/kwab183· OSTI ID:1819600
 [1];  [1];  [1];  [2];  [3];  [3];  [1];  [4];  [1];  [4];  [4];  [5];  [6];  [4];  [7];  [7];  [4];  [8];  [3];  [9] more »;  [8] « less
  1. US Department of Veterans Affairs, Boston, MA (United States)
  2. US Department of Veterans Affairs, West Haven, CT (United States); London School of Hygiene and Tropical Medicine (United Kingdom)
  3. US Department of Veterans Affairs, West Haven, CT (United States); Yale Univ., New Haven, CT (United States)
  4. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
  5. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States)
  6. US Department of Veterans Affairs, Nashville, TN (United States); Vanderbilt Univ. Medical Center, Nashville, TN (United States)
  7. US Department of Veterans Affairs, Washington, DC (United States)
  8. US Department of Veterans Affairs, Boston, MA (United States); Brigham and Women's Hospital (Harvard Medical School), Boston, MA (United States)
  9. US Department of Veterans Affairs, Boston, MA (United States); Boston Univ., MA (United States)
+ Show Author Affiliations
Hydroxychloroquine (HCQ) was proposed as an early therapy for coronavirus disease 2019 (COVID-19) after in vitro studies indicated possible benefit. Previous in vivo observational studies have presented conflicting results, though recent randomized clinical trials have reported no benefit from HCQ amongst hospitalized COVID-19 patients. In this work, we examined the effects of HCQ alone, and in combination with azithromycin, in a hospitalized COVID-19 positive, United States (US) Veteran population using a propensity score adjusted survival analysis with imputation of missing data. From March 1, 2020 through April 30, 2020, 64,055 US Veterans were tested for COVID-19 based on Veteran Affairs Healthcare Administration electronic health record data. Of the 7,193 positive cases, 2,809 were hospitalized, and 657 individuals were prescribed HCQ within the first 48-hours of hospitalization for the treatment of COVID-19. There was no apparent benefit associated with HCQ receipt, alone or in combination with azithromycin, and an increased risk of intubation when used in combination with azithromycin [Hazard Ratio (95% Confidence Interval): 1.55 (1.07, 2.24)]. In conclusion, we assessed the effectiveness of HCQ with or without azithromycin in treating patients hospitalized with COVID-19 using a national sample of the US Veteran population. Using rigorous study design and analytic methods to reduce confounding and bias, we found no evidence of a survival benefit from the administration of HCQ.
Research Organization:
Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
Sponsoring Organization:
National Institutes of Health (NIH); US Department of Veterans Affairs; USDOE Laboratory Directed Research and Development (LDRD) Program
Grant/Contract Number:
AC05-00OR22725
OSTI ID:
1819600
Journal Information:
American Journal of Epidemiology, Journal Name: American Journal of Epidemiology Journal Issue: 11 Vol. 190; ISSN 0002-9262
Publisher:
Oxford University PressCopyright Statement
Country of Publication:
United States
Language:
English

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Related Subjects

60 APPLIED LIFE SCIENCES
covid-19
gradient boosting
hydroxychloroquine
pharmacoepidemiology
propensity score
survival analysis
treatment outcome