Johnston: Hydroxychloroquine with or Without Azithromycin for Treatment of Early SARS-CoV-2 Infection Among High-Risk Outpatient Adults: A Randomized Clinical Trial [HCQ]

Hydroxychloroquine with or Without Azithromycin for Treatment of Early SARS-CoV-2 Infection Among High-Risk Outpatient Adults: A Randomized Clinical Trial

Johnston et al., EClinicalMedicine, doi:10.1016/j.eclinm.2021.100773 (date from earlier preprint), NCT04354428 (history)

Johnston et al., Hydroxychloroquine with or Without Azithromycin for Treatment of Early SARS-CoV-2 Infection Among High-Risk.., EClinicalMedicine, doi:10.1016/j.eclinm.2021.100773 (date from earlier preprint), NCT04354428

Dec 2020 Source PDF

Twitter
Facebook

All Studies Meta

Small early terminated late treatment RCT comparing vitamin C + folic acid, HCQ + folic acid, and HCQ+AZ, showing non-statistically significantly lower hospitalization with HCQ/HCQ+AZ, and faster viral clearance with HCQ. Enrollment was a median of 5.9 days after onset (6.2 and 6.3 in the treatment arms).

The median time to viral clearance for vitamin C + folic acid was 8 days in the preprint but changed to 7 days in the published paper without explanation.

Low risk patients, median age 37, no deaths (not matching the title which claims "high risk"). Post hoc addition of a new Ct threshold to obscure the statistically significant faster clearance. No analysis for time from symptom onset. Authors identify (relatively) low and high risk cohorts, but do not provide either viral shedding or symptom resolution results for the cohorts. NCT04354428 (history). For other issues see [twitter.com].

1. twitter.com, https://twitter.com/Covid19Crusher/status/1358066110105542658.

Important missing comments or errors? Let us know.

risk of hospitalization, 29.9% lower, RR 0.70, p = 0.73, treatment 5 of 148 (3.4%), control 4 of 83 (4.8%), NNT 69, HCQ + folic acid and HCQ + AZ vs. vitamin C + folic acid.

risk of no recovery, 2.0% lower, RR 0.98, p = 0.95, treatment 30 of 60 (50.0%), control 34 of 72 (47.2%), adjusted per study, inverted to make RR<1 favor treatment, HCQ + folic acid vs. vitamin C + folic acid.

risk of no recovery, 9.9% higher, RR 1.10, p = 0.70, treatment 34 of 65 (52.3%), control 34 of 72 (47.2%), adjusted per study, inverted to make RR<1 favor treatment, HCQ + AZ vs. vitamin C + folic acid.

time to viral-, 28.6% lower, relative time 0.71, treatment 49, control 52, median time, HCQ + folic acid vs. vitamin C + folic acid.

time to viral-, 14.3% lower, relative time 0.86, treatment 51, control 52, median time, HCQ + AZ vs. vitamin C + folic acid.

risk of no viral clearance, 38.3% lower, RR 0.62, p = 0.047, treatment 6 of 49 (12.2%), control 12 of 52 (23.1%), NNT 9.2, adjusted per study, inverted to make RR<1 favor treatment, HCQ + folic acid vs. vitamin C + folic acid.

risk of no viral clearance, 20.0% lower, RR 0.80, p = 0.49, treatment 11 of 51 (21.6%), control 12 of 52 (23.1%), adjusted per study, inverted to make RR<1 favor treatment, HCQ + AZ vs. vitamin C + folic acid.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Johnston et al., 9 Dec 2020, Randomized Controlled Trial, USA, peer-reviewed, 30 authors, average treatment delay 5.9 days, dosage 400mg bid day 1, 200mg bid days 2-10, trial NCT04354428 (history).

All Studies Meta Analysis Submit Updates or Corrections

This Paper HCQ All

Abstract: EClinicalMedicine 33 (2021) 100773 Contents lists available at ScienceDirect EClinicalMedicine journal homepage: https://www.journals.elsevier.com/eclinicalmedicine Research Paper Hydroxychloroquine with or without azithromycin for treatment of early SARS-CoV-2 infection among high-risk outpatient adults: A randomized clinical trial Christine Johnstona,b,h,*, Elizabeth R. Brownc,h,i, Jenell Stewarta,e, Helen C.Stankiewicz Karitaa, Patricia J. Kissingerj, John Dwyerk, Sybil Hosekl,m, Temitope Oyedelel,m, Michael K. Paasche-Orlown,o, Kristopher Paolinop, Kate B. Hellere, Hannah Leingange, Harald S. Haugene, Tracy Q. Dongh, Anna Bershteynq, Arun R. Sridharf, Jeanne Poolef, Peter A. Noseworthyr, Michael J. Ackermanr, Susan Morrisone, Alexander L. Greningerb,h, Meei-Li Huangh, Keith R. Jeromeb,h, Mark H. Wenerb,g, Anna Walda,b,d,h, Joshua T. Schiffera,h, Connie Celuma,d,e, Helen Y. Chua,d,e, Ruanne V. Barnabasa,b,d,h, Jared M. Baetena,d,e, for the COVID-19 Early Treatment Study Team a Division of Allergy and Infectious Diseases, University of Washington, United States Department of Laboratory Medicine and Pathology, University of Washington, United States c Department of Biostatistics, University of Washington, United States d Department of Epidemiology, University of Washington, United States e Department of Global Health, University of Washington, United States f Division of Cardiology, University of Washington, United States g Division of Rheumatology, University of Washington, Seattle, WA, United States h Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA i Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States j School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, United States k School of Medicine, Tulane University, New Orleans, LA, United States l John H. Stroger, Jr., Hospital of Cook County, Chicago, IL, United States m Rush University Medical Center, Chicago, IL, United States n Boston University School of Medicine, Boston, MA, United States o Boston Medical Center, Boston, MA, United States p State University of New York Upstate Medical University, Syracuse, NY, United States q New York University Grossman School of Medicine, NY, NY, United States r Mayo Clinic, Rochester, MN, United States b A R T I C L E I N F O Article History: Received 23 December 2020 Revised 8 February 2021 Accepted 10 February 2021 Available online 27 February 2021 Keywords: Coronavirus COVID-19 SARS-CoV-2 Hydroxychloroquine Azithromycin Early treatment Remote enrollment Randomized controlled trial A B S T R A C T Background: Treatment options for outpatients with COVID-19 could reduce morbidity and prevent SARSCoV-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..

Late treatment
is less effective

Please send us corrections, updates, or comments. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.

Submit