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

• ClinicalTrials.gov Identifier: NCT04363203
• Recruitment Status: Suspended
• First Posted: April 27, 2020
• Last Update Posted: June 22, 2020
• Sponsor: Salomeh Keyhani MD
• Collaborator: San Francisco VA Health Care System
• Information provided by (Responsible Party): Salomeh Keyhani MD, San Francisco VA Health Care System

Study Description

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.

Condition or disease	Intervention/treatment	Phase
SARS-CoV-2; COVID-19	Drug: Hydroxychloroquine; Drug: Azithromycin; Drug: Placebo oral tablet	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• 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.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Eligible, consented patients will be randomized to a 1:1:1 treatment allocation, stratifying by age (<65, 65 or more) and region, and using randomly permutated blocks (block size of 3) within study site. Pharmacy is unblinded to study drugs.
• Primary Purpose: Treatment
• Official Title: VA Remote and Equitable Access to COVID-19 Healthcare Delivery (VA-REACH TRIAL)
• Actual Study Start Date: April 30, 2020
• Estimated Primary Completion Date: March 2021
• Estimated Study Completion Date: August 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Days to resolution of cough, fever and shortness of breath [ Time Frame: 30-days ]

Secondary Outcome Measures :

1. Days to resolution of all COVID-19 symptoms [ Time Frame: 30-days ]
2. All cause hospitalization [ Time Frame: 30-days ]
3. All cause mortality [ Time Frame: 30-days ]
4. COVID-19 specific mortality [ Time Frame: 30-days ]
5. COVID-19 specific hospitalization [ Time Frame: 30-days ]

Eligibility Criteria

• Ages Eligible for Study: 216 Months and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

San Francisco VA

San Francisco, California, United States, 94121

Sponsors and Collaborators

Salomeh Keyhani MD

San Francisco VA Health Care System

Investigators

• Principal Investigator: Salomeh Keyhani, MD MPH; San Francisco VA/University of California, San Francisco

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Salomeh Keyhani MD, Professor of Medicine, University of California San Francisco, San Francisco VA Health Care System
• ClinicalTrials.gov Identifier: NCT04363203
• Other Study ID Numbers: 20-30517
• First Posted: April 27, 2020
• Last Update Posted: June 22, 2020
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

COVID-19; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Azithromycin; Hydroxychloroquine; Anti-Bacterial Agents; Anti-Infective Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents