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

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.

Study Overview

• Status: Suspended
• Conditions: COVID-19; SARS-CoV-2
• Intervention / Treatment: Drug: Hydroxychloroquine; Drug: Azithromycin; Drug: Placebo oral tablet

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.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94121
      • San Francisco VA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Hydroxychloroquine; 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; 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.
Active Comparator: Azithromycin; Azithromycin: 2x250mg by mouth (PO) in the AM followed by 250mg PO every day 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.
Placebo Comparator: Placebo; The pills packs for the 3 arms are identical.	Drug: Placebo oral tablet; Placebo in pill packs identical to study drugs

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Salomeh Keyhani MD
• Collaborators: San Francisco VA Health Care System
• Investigators: Principal Investigator: Salomeh Keyhani, MD MPH, San Francisco VA/University of California, San Francisco

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2020
• Primary Completion (Anticipated): March 1, 2021
• Study Completion (Anticipated): August 1, 2021

Study Registration Dates

• First Submitted: April 23, 2020
• First Submitted That Met QC Criteria: April 24, 2020
• First Posted (Actual): April 27, 2020

Study Record Updates

• Last Update Posted (Actual): June 22, 2020
• Last Update Submitted That Met QC Criteria: June 18, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Azithromycin; Hydroxychloroquine
• Other Study ID Numbers: 20-30517

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No