Hydroxychloroquine with or without azithromycin for treatment of early SARS-CoV-2 infection among high-risk outpatient adults: A randomized clinical trial
Christine Johnston, Elizabeth R Brown, Jenell Stewart, Helen C Stankiewicz Karita, Patricia J Kissinger, John Dwyer, Sybil Hosek, Temitope Oyedele, Michael K Paasche-Orlow, Kristopher Paolino, Kate B Heller, Hannah Leingang, Harald S Haugen, Tracy Q Dong, Anna Bershteyn, Arun R Sridhar, Jeanne Poole, Peter A Noseworthy, Michael J Ackerman, Susan Morrison, Alexander L Greninger, Meei-Li Huang, Keith R Jerome, Mark H Wener, Anna Wald, Joshua T Schiffer, Connie Celum, Helen Y Chu, Ruanne V Barnabas, Jared M Baeten
EClinicalMedicine, doi:10.1016/j.eclinm.2021.100773
Background: Treatment options for outpatients with COVID-19 could reduce morbidity and prevent SARS-CoV-2 transmission. Methods: In this randomized, double-blind, three-arm (1:1:1) placebo-equivalent controlled trial conducted remotely throughout the United States, adult outpatients with laboratory-confirmed SARS-CoV-2 infection were recruited. Participants were randomly assigned to receive hydroxychloroquine (HCQ) (400 mg BID x1day, followed by 200 mg BID x9days) with or without azithromycin (AZ) (500 mg, then 250 mg daily x4days) or placebo-equivalent (ascorbic acid (HCQ) and folic acid (AZ)), stratified by risk for progression to severe COVID-19 (high-risk vs. low-risk). Self-collected nasal swabs for SARS-CoV-2 PCR, FLUPro symptom surveys, EKGs and vital signs were collected daily. Primary endpoints were: (a) 14-day progression to lower respiratory tract infection (LRTI), 28-day COVID-19 related hospitalization, or death; (b) 14-day time to viral clearance; secondary endpoints included time to symptom resolution (ClinicalTrials.gov: NCT04354428). Due to the low rate of clinical outcomes, the study was terminated for operational futility. Findings: Between 15th April and 27th July 2020, 231 participants were enrolled and 219 initiated medication a median of 5.9 days after symptom onset. Among 129 high-risk participants, incident LRTI occurred in six (4.7%) participants (two control, four HCQ/AZ) and COVID-19 related hospitalization in seven (5.4%
Supplementary materials Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.eclinm.2021.100773.
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