Azithromycin for COVID-19 Treatment in Outpatients Nationwide

Phase 3

Terminated

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.

Recruitment & Eligibility

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

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Placebo	Placebos	Matching placebo
Azithromycin	Azithromycin	1.2g of oral azithromycin

Primary Outcome Measures

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

Secondary Outcome Measures

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