VA Remote and Equitable Access to COVID-19 Healthcare Delivery (VA-REACH TRIAL)

Study Overview
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Brief Summary
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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
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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.

Official Title
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VA Remote and Equitable Access to COVID-19 Healthcare Delivery (VA-REACH TRIAL)

Conditions
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SARS-CoV-2, COVID-19

Intervention / Treatment
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* Drug: Hydroxychloroquine
* Drug: Azithromycin
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 216 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional 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.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hydroxychloroquine<br>Hydroxychloroquine: 2x200mg mg PO in the AM and 2x200mg PO in the PM on Day 1, followed by 200mg capsule in the AM and 200 mg in the PM on Days 2-5 | Drug: Hydroxychloroquine<br>* 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.<br>|
| Active Comparator: Azithromycin<br>Azithromycin: 2x250mg by mouth (PO) in the AM followed by 250mg PO every day on days 2-5 | Drug: Azithromycin<br>* Azithromycin: 2x250mg by mouth (PO) in the AM on Day 1, followed by 250mg PO every day on Days 2-5.<br>|
| Placebo Comparator: Placebo<br>The pills packs for the 3 arms are identical. | Drug: Placebo oral tablet<br>* Placebo in pill packs identical to study drugs<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days to resolution of cough, fever and shortness of breath |  | 30-days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days to resolution of all COVID-19 symptoms |  | 30-days | 
| All cause hospitalization |  | 30-days | 
| All cause mortality |  | 30-days | 
| COVID-19 specific mortality |  | 30-days | 
| COVID-19 specific hospitalization |  | 30-days |