Azithromycin for COVID-19 Treatment in Outpatients Nationwide (ACTION)

Azithromycin for Prevention of Disease Progression in Patients With Mild or Moderate COVID-19

This individually randomized telemedicine-based trial aims to evaluate the efficacy of a single dose of azithromycin for prevention of progression of COVID-19 in patients with a recent positive SARS-CoV-2 test who are not currently hospitalized.

Study Overview

• Status: Terminated
• Conditions: COVID-19; SARS-CoV-2
• Intervention / Treatment: Drug: Azithromycin; Drug: Placebos

Detailed Description

Identification of a safe, effective treatment for individuals with mild or moderate COVID-19 that prevents disease progression and reduces hospitalization would reduce the burden on the health system. High dose hydroxychloroquine is being evaluated for SARS-CoV-2 prevention and COVID-19 disease treatment, but has a high risk of a number of potentially severe adverse events. Recent evidence has indicated that the broad-spectrum macrolide azithromycin may have some activity against coronaviruses. Here we propose an individually-randomized, placebo-controlled trial to determine the efficacy of a single dose of azithromycin for prevention of COVID-19.

Potential participants will undergo remote eligibility screening with study staff prior to enrollment. Upon determination of eligibility and signing electronic informed consent documents, participants will be emailed baseline study forms and will be mailed their randomized study treatment. At the end of the study (21 days), participants will be emailed a final study questionnaire. Note that there will no contact between study staff and participants in this trial, minimizing risk of infection spread.

• Study Type: Interventional
• Enrollment (Actual): 263
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California San Francisco

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:

• Evidence of a positive SARS-CoV-2 test and test results received within the previous seven days
• Not currently hospitalized
• Willing and able to receive study drug by mail
• Willing and able to do the study questionnaires at baseline, day 3, 7, 14, 21 days via email or over the phone
• No known allergy or other contraindication to macrolides
• Age 18 years or older at the time of enrollment
• No known history of prolongation of the QT interval (eg. History of torsades de pointes, congenital long QT syndrome, bradyarrhthmia)
• No recent use of hydroxychloroquine within the past 7 days for participants >55 years of age
• Not currently taking nelfinavir or warfarin (Coumadin)
• Provision of informed consent
• Not currently pregnant

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching placebo	Drug: Placebos; Participants will be shipped a dose of matching placebo
Experimental: Azithromycin; 1.2g of oral azithromycin	Drug: Azithromycin; Participants will be shipped a single 1.2 g dose of oral azithromycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Were Symptom Free at Day 14	Binary assessment of whether the participant is experiencing any symptoms at Day 14 (yes or no)	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	All-cause mortality	14 days
Adverse Events	Percentage of participants experiencing adverse events, including gastrointestinal side effects and rash	3 days
Positive SARS-CoV-2 Test - Nasal Swab	Prevalence of positive SARS-CoV-2 test by self-collected nasal swab	3 days
Positive SARS-CoV-2 Test - Saliva Swab	Prevalence of positive SARS-CoV-2 test by self-collected saliva swab	3 days
Positive SARS-CoV-2 Test - Rectal Swab	Prevalence of positive SARS-CoV-2 test by self-collected rectal swab	3 days
Genetic Macrolide Resistance Determinants	Prevalence of genetic macrolide resistance determinants by self-collected rectal swab	3 days
Secondary Outcomes Through Day 21	Prevalence of cough, fever, myalgia, anosmia, shortness of breath, fatigue, conjunctivitis, and orthostatic symptoms through Day 21	Cumulative over 21 days reported (assessed at 3, 7, 14, 21 days)
Number of Participants With Emergency Room Visits	Number of emergency room visits <24 hours	21 days
Number of Household Members With COVID-19 (Confirmed or Symptomatic)	Number of household members with confirmed or symptomatic COVID-19 through Day 21	21 days
Number of Participants That Died	Deaths within the study	21 days
Number of Participants Reporting Hospitalization	Number of hospitalizations defined as a hospital stay or ER stay longer than 24 hours through 21 days post enrollment	21 Days
Viral Load - Nasal Swab	Viral load by self-collected nasal swab	3 days
Viral Load - Saliva Swab	Viral load by self-collected saliva swab	3 days

Collaborators and Investigators

• Sponsor: Thomas M. Lietman
• Collaborators: Pfizer; Bill and Melinda Gates Foundation; Stanford University

Publications and helpful links

General Publications

• Oldenburg CE, Pinsky BA, Brogdon J, Chen C, Ruder K, Zhong L, Nyatigo F, Cook CA, Hinterwirth A, Lebas E, Redd T, Porco TC, Lietman TM, Arnold BF, Doan T. Effect of Oral Azithromycin vs Placebo on COVID-19 Symptoms in Outpatients With SARS-CoV-2 Infection: A Randomized Clinical Trial. JAMA. 2021 Aug 10;326(6):490-498. doi: 10.1001/jama.2021.11517.

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2020
• Primary Completion (Actual): March 16, 2021
• Study Completion (Actual): March 30, 2021

Study Registration Dates

• First Submitted: March 30, 2020
• First Submitted That Met QC Criteria: April 1, 2020
• First Posted (Actual): April 2, 2020

Study Record Updates

• Last Update Posted (Actual): March 2, 2023
• Last Update Submitted That Met QC Criteria: February 1, 2023
• Last Verified: February 1, 2023

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; Anti-Infective Agents; Anti-Bacterial Agents; Azithromycin
• Other Study ID Numbers: 20-30504

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No