Hydroxychloroquine vs. Azithromycin for Hospitalized Patients with COVID-19 (HAHPS): Results of a Randomized, Active Comparator Trial
Brown et al.
, Hydroxychloroquine vs. Azithromycin for Hospitalized Patients with COVID-19 (HAHPS): Results of a Randomized,..
, Annals of the American Thoracic Society, doi:10.1513/AnnalsATS.202008-940OC
Small early terminated very late stage (86% on oxygen, 44% enrolled in the ICU) RCT comparing HCQ vs. AZ, not finding a significant difference between the two treatments. There is no comparison with a control group. HCQ patients not in the ICU at enrollment (slightly earlier treatment) did better, OR 0.95 vs. 1.13.
HCQ dosage is relatively low:
Dose in first 24 hours - 1g (compare to Boulware et al. 2g)
Dose in 5 days - 2.4g (compare to Boulware et al. 3.8g)
Brown et al., 9 Nov 2020, peer-reviewed, 17 authors.
Abstract: ORIGINAL RESEARCH
Hydroxychloroquine versus Azithromycin for Hospitalized Patients
Results of a Randomized, Active Comparator Trial
Samuel M. Brown1,2*, Ithan Peltan1,2, Naresh Kumar1,3, Lindsay Leither1,2, Brandon J. Webb3,4,5, Nathan Starr6,7,
Colin K. Grissom1,2, Whitney R. Buckel8, Rajendu Srivastava9,10, Allison M. Butler1, Danielle Groat1, Benjamin Haaland11,
Jian Ying11, Estelle Harris2, Stacy Johnson7, Robert Paine III2, and Tom Greene11
Pulmonary and Critical Care Medicine, 3Infectious Diseases, and 6Hospital Medicine, Intermountain Medical Center, Murray,
Utah; 2Pulmonary and Critical Care Medicine, 4Infectious Diseases, 7Hospital Medicine, 9Pediatric Inpatient Medicine, and 11Division of
Biostatistics, Population Health Sciences, University of Utah, Salt Lake City, Utah; 5Infectious Diseases, Stanford University, Stanford,
California; and 8Pharmacy Services and 10Healthcare Delivery Institute, Intermountain Healthcare, Murray, Utah
ORCID IDs: 0000-0003-1206-6261 (S.M.B.); 0000-0003-1730-234X (I.P.); 0000-0002-1799-3315 (B.J.W.); 0000-0001-9505-2572 (W.R.B.).
Rationale: The coronavirus disease (COVID-19) pandemic struck
an immunologically naive, globally interconnected population. In
the face of a new infectious agent causing acute respiratory failure
for which there were no known effective therapies, rapid, often
pragmatic trials were necessary to evaluate potential treatments,
frequently starting with medications that are already marketed for
other indications. Early in the pandemic, hydroxychloroquine and
azithromycin were two such candidates.
Objectives: To assess the relative efﬁcacy of hydroxychloroquine
and azithromycin among hospitalized patients with COVID-19.
Methods: We performed a randomized clinical trial of
hydroxychloroquine versus azithromycin among hospitalized
patients with COVID-19. Treatment was 5 days of study medication.
The primary endpoint was the COVID ordinal outcomes scale at
Day 14. Secondary endpoints included hospital-, intensive care
unit–, and ventilator-free days at Day 28. The trial was stopped early
after the enrollment of 85 patients when a separate clinical trial
concluded that a clinically important effect of hydroxychloroquine
over placebo was deﬁnitively excluded. Comparisons were made a
priori using a proportional odds model from a Bayesian perspective.
Results: We enrolled 85 patients at 13 hospitals over 11 weeks.
Adherence to study medication was high. The estimated odds ratio
for less favorable status on the ordinal scale for hydroxychloroquine
versus azithromycin from the primary analysis was 1.07, with a 95%
credible interval from 0.63 to 1.83 with a posterior probability of
60% that hydroxychloroquine was worse than azithromycin.
Secondary outcomes displayed a similar slight preference for
azithromycin over hydroxychloroquine. QTc prolongation
was rare and did not differ between groups. The 20 safety
outcomes were similar between arms, with the possible exception
of postrandomization-onset acute kidney injury, which was
more common with hydroxychloroquine (15% vs. 0%). Patients
in the hydroxychloroquine arm received remdesivir more often
than those in the azithromycin arm (19% vs. 2%). There was no
apparent association between remdesivir use and acute kidney injury.
Conclusions: Although early termination limits the precision of
our results, we found no suggestion of substantial efﬁcacy for
hydroxychloroquine over azithromycin. Acute kidney injury may..
is less effective
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