Azithromycin for COVID-19 Treatment in Outpatients Nationwide

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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COVID-19, SARS-CoV-2

Intervention / Treatment
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* Drug: Azithromycin
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 | 
| 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 |