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

Tracking Information

• First Submitted Date: March 30, 2020
• First Posted Date: April 2, 2020
• Results First Submitted Date: August 9, 2021
• Results First Posted Date: September 9, 2021
• Last Update Posted Date: March 2, 2023
• Actual Study Start Date: May 22, 2020
• Actual Primary Completion Date: March 16, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 23, 2021)

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)

Original Primary Outcome Measures (submitted: April 1, 2020)

Hospitalization [ Time Frame: 14 days ]

All-cause hospitalization

Current Secondary Outcome Measures (submitted: February 1, 2023)

• Viral Load - Nasal Swab [ Time Frame: 3 days ]
  Viral load by self-collected nasal swab
• Viral Load - Saliva Swab [ Time Frame: 3 days ]
  Viral load by self-collected saliva swab
• Mortality [ Time Frame: 14 days ]
  All-cause mortality
• Adverse Events [ Time Frame: 3 days ]
  Percentage of participants experiencing adverse events, including gastrointestinal side effects and rash
• Positive SARS-CoV-2 Test - Nasal Swab [ Time Frame: 3 days ]
  Prevalence of positive SARS-CoV-2 test by self-collected nasal swab
• Positive SARS-CoV-2 Test - Saliva Swab [ Time Frame: 3 days ]
  Prevalence of positive SARS-CoV-2 test by self-collected saliva swab
• Positive SARS-CoV-2 Test - Rectal Swab [ Time Frame: 3 days ]
  Prevalence of positive SARS-CoV-2 test by self-collected rectal swab
• Genetic Macrolide Resistance Determinants [ Time Frame: 3 days ]
  Prevalence of genetic macrolide resistance determinants by self-collected rectal swab
• 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
• Number of Participants With Emergency Room Visits [ Time Frame: 21 days ]
  Number of emergency room visits <24 hours
• 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
• Number of Participants That Died [ Time Frame: 21 days ]
  Deaths within the study
• 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

Original Secondary Outcome Measures (submitted: April 1, 2020)

• Viral load [ Time Frame: 7 days ]
  Viral load by self-collected nasal swab
• Viral load [ Time Frame: 7 days ]
  Viral load by self-collected saliva swab
• Mortality [ Time Frame: 14 days ]
  All-cause mortality

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Azithromycin for COVID-19 Treatment in Outpatients Nationwide
• Official Title: Azithromycin for Prevention of Disease Progression in Patients With Mild or Moderate COVID-19
• 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.

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
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• COVID-19
• SARS-CoV-2

Intervention

• Drug: Azithromycin
  Participants will be shipped a single 1.2 g dose of oral azithromycin
• Drug: Placebos
  Participants will be shipped a dose of matching placebo

Study Arms

• Experimental: Azithromycin
  1.2g of oral azithromycin
  Intervention: Drug: Azithromycin
• Placebo Comparator: Placebo
  Matching placebo
  Intervention: Drug: Placebos

• 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: August 9, 2021): 263
• Original Estimated Enrollment (submitted: April 1, 2020): 2271
• Actual Study Completion Date: March 30, 2021
• Actual Primary Completion Date: March 16, 2021 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04332107
• Other Study ID Numbers: 20-30504
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

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

• Current Responsible Party: Thomas M. Lietman, University of California, San Francisco
• Original Responsible Party: University of California, San Francisco
• Current Study Sponsor: Thomas M. Lietman
• Original Study Sponsor: University of California, San Francisco

Collaborators

• 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

• PRS Account: University of California, San Francisco
• Verification Date: February 2023