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

• ClinicalTrials.gov Identifier: NCT04332107
• Recruitment Status: Terminated
• First Posted: April 2, 2020
• Results First Posted: September 9, 2021
• Last Update Posted: March 2, 2023
• Sponsor: Thomas M. Lietman
• Collaborators: Bill and Melinda Gates Foundation; Pfizer; Stanford University
• Information provided by (Responsible Party): Thomas M. Lietman, University of California, San Francisco

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
COVID-19; SARS-CoV-2	Drug: Azithromycin; Drug: Placebos	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 263 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Azithromycin for Prevention of Disease Progression in Patients With Mild or Moderate COVID-19
• Actual Study Start Date: May 22, 2020
• Actual Primary Completion Date: March 16, 2021
• Actual Study Completion Date: March 30, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of Participants Who Were Symptom Free at Day 14 [ Time Frame: 14 days ]
   Binary assessment of whether the participant is experiencing any symptoms at Day 14 (yes or no)

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

University of California San Francisco

San Francisco, California, United States, 94143

Sponsors and Collaborators

Thomas M. Lietman

Bill and Melinda Gates Foundation

Pfizer

Stanford University

Investigators

• Principal Investigator: Catherine Oldenburg, ScD, MPH; University of California, San Francisco
• Principal Investigator: Thuy Doan, MD, PhD; University of California, San Francisco

  Study Documents (Full-Text)

Documents provided by Thomas M. Lietman, University of California, San Francisco:

Study Protocol  [PDF] April 5, 2021

Statistical Analysis Plan  [PDF] May 29, 2020

More Information

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

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.

• Responsible Party: Thomas M. Lietman, Professor, University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT04332107
• Other Study ID Numbers: 20-30504
• First Posted: April 2, 2020
• Results First Posted: September 9, 2021
• Last Update Posted: March 2, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

• 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

Additional relevant MeSH terms:

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Azithromycin; Anti-Bacterial Agents; Anti-Infective Agents