Clinical trial NCT04363203: VA Remote and Equitable Access to COVID-19 Healthcare Delivery (VA-REACH TRIAL)
Official title: VA Remote and Equitable Access to COVID-19 Healthcare Delivery (VA-REACH TRIAL)
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE3
Conditions: SARS-CoV-2
COVID-19
Lead sponsor: San Francisco VA Health Care System
Sponsor class: FED
Collaborators: name: San Francisco VA Health Care System
First posted: 2020-04-27
Enrollment: 300
Sex: ALL
Minimum age (years): 216
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: A 3-arm RCT to determine the efficacy of hydroxychloroquine or azithromycin compared to placebo in treating mild to moderate COVID-19 among Veterans in the outpatient setting.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Days to resolution of cough, fever and shortness of breath
timeFrame: 30-days
Secondary outcomes:
measure: Days to resolution of all COVID-19 symptoms
timeFrame: 30-days
measure: All cause hospitalization
timeFrame: 30-days
measure: All cause mortality
timeFrame: 30-days
measure: COVID-19 specific mortality
timeFrame: 30-days
measure: COVID-19 specific hospitalization
timeFrame: 30-days
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: San Francisco VA
state: California
Study officials:
affiliation: San Francisco VA/University of California, San Francisco
name: Salomeh Keyhani, MD MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Keyhani S, Kelly JD, Bent S, Boscardin WJ, Shlipak MG, Leonard S, Abraham A, Lum E, Lau N, Austin C, Oldenburg CE, Zillich A, Lopez L, Zhang Y, Lietman T, Bravata DM. A telehealth-based randomized controlled trial: A model for outpatient trials of off-label medications during the COVID-19 pandemic. Clin Trials. 2021 Aug;18(4):514-517. doi: 10.1177/17407745211011577. Epub 2021 May 20.