We propose a 3-arm RCT to determine the efficacy of hydroxychloroquine or azithromycin in treating mild to moderate COVID-19 among Veterans in the outpatient setting.
SARS-CoV-2 is a novel coronavirus disease (COVID-19) that presents with fever, cough, and
shortness of breath, and has a mortality rate of 2-4%. Outcomes are worse among the elderly
and those with cardiovascular, respiratory, cancer and other co-morbidities. Several
treatments are also emerging as promising therapeutic candidates, hydroxychloroquine and
azithromycin - both available as generic pills and widely used for other indications - are
potential options for treatment. A small randomized controlled trial (RCT) of hospitalized
patients suggests chloroquine may be superior to placebo in promoting viral elimination and
shortening disease course. Hydroxychloroquine is preferred to chloroquine in the U.S. A small
non-randomized trial found azithromycin had a clinical benefit. When azithromycin and
hydroxychloroquine are given together, they can cause cardiac side-effects that limit use in
the outpatient setting. These drugs, however, have independent potential benefits against
COVID-19 that require more rigorous study before either is considered standard of care. We
propose a 3-arm RCT to determine the efficacy of hydroxychloroquine or azithromycin in
treating mild to moderate COVID-19 among Veterans in the outpatient setting.
Drug: Hydroxychloroquine
Hydroxychloroquine: 2x200mg mg .PO in the AM and 2x200mg PO in the PM on Day 1, followed by 200mg PO in the AM and 200 mg PO in the PM on Days 2-5.
Drug: Azithromycin
Azithromycin: 2x250mg by mouth (PO) in the AM on Day 1, followed by 250mg PO every day on Days 2-5.
Drug: Placebo oral tablet
Placebo in pill packs identical to study drugs
Inclusion Criteria:
- willingness to take the study drug and ability to take oral medications
- able to be contacted by phone
- willing and able to give informed consent for participation in the study and agrees
with its conduct and willing to email the study team a picture of their consent form
Exclusion Criteria:
Exclusion Criteria Based on National VA Data:
We will exclude individuals based on the following national VA data and chart review
criteria:
- eGFR <30mL/min or dialysis
- aspartate transaminase (AST) or alanine transaminase (ALT) >5 times the upper limit of
normal or cirrhosis in past 2 years
- hypersensitivity to chloroquine, hydroxychloroquine or other 4-aminoquinolines (e.g.,
amodiaquine), azithromycin or macrolides
- already taking hydroxychloroquine or azithromycin
- congestive heart failure with an ejection fraction (EF) <35% in past 2 years or
hospitalization within past 6 months
- concomitant treatment with any QT prolonging drug
- history of cardiac arrest, ventricular fibrillation or ventricular tachycardia in past
5 years
- QT prolongation on any ECG in past 5 years
- potassium <3.5 meq/l in labs in past 2 years
- magnesium< 1/5 meq/l in any lab in past 2 years
- any patient who has not had follow-up with their primary care doctors in past 2 years
- any Veteran who cannot follow-up such as those with dementia, home based primary care
or those with active psychosis documented in past 2 years
- G6PD deficiency
Exclusions Based on Baseline Interview:
- any female who is breastfeeding or pregnant or planning to become pregnant.
- any Veteran who receives most of their care in non-VA settings
- Veteran enrolled in another COVID Trial
- Veteran received a prescription for azithromycin and hydroxychloroquine
- Veteran allergic to azithromycin and or hydroxychloroquine
- Veteran receiving QT prolonging drugs from non-VA pharmacy
San Francisco VA
San Francisco, California, United States
Salomeh Keyhani, MD MPH, Principal Investigator
San Francisco VA/University of California, San Francisco