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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04332107
Recruitment Status : Terminated (Futility)
First Posted : April 2, 2020
Results First Posted : September 9, 2021
Last Update Posted : October 7, 2021
Sponsor:
Collaborators:
Bill and Melinda Gates Foundation
Pfizer
Stanford University
Information provided by (Responsible Party):
Thomas M. Lietman, University of California, San Francisco

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions COVID-19
SARS-CoV-2
Interventions Drug: Azithromycin
Drug: Placebos
Enrollment 263
Recruitment Details Between May 22, 2020 and March 16, 2021, 604 participants were screened and 263 participants were enrolled. All study recruitment and enrollment was done remotely.
Pre-assignment Details Common reasons for ineligibility included a negative COVID-19 test result (n=70), a COVID-19 test result outside of the 7 day window (n=118), could not be reached for consent (n=73), and under the age of 18 (19). A total of 341 screened participants were excluded.
Arm/Group Title Azithromycin Placebo
Hide Arm/Group Description

1.2g of oral azithromycin

Azithromycin: Participants will be shipped a single 1.2 g dose of oral azithromycin

Matching placebo

Placebos: Participants will be shipped a dose of matching placebo

Period Title: Day 3
Started 171 92
Completed 145 72
Not Completed 26 20
Reason Not Completed
Lost to Follow-up             23             14
Missing outcome data             3             6
Period Title: Day 14
Started 148 [1] 78 [1]
Completed 131 70
Not Completed 17 8
Reason Not Completed
Lost to Follow-up             13             4
Missing outcome data             4             4
[1]
Those who had missing measurements at Day 3 but were not completely lost-to-followup were allowed to continue with the trial.
Period Title: Day 21
Started 135 [1] 74 [1]
Completed 125 72
Not Completed 10 2
Reason Not Completed
Lost to Follow-up             10             2
[1]
Those who had missing measurements at Day 14 but were not completely lost-to-followup were allowed to continue with the trial.
Arm/Group Title Azithromycin Placebo Total
Hide Arm/Group Description

1.2g of oral azithromycin

Azithromycin: Participants will be shipped a single 1.2 g dose of oral azithromycin

Matching placebo

Placebos: Participants will be shipped a dose of matching placebo

Total of all reporting groups
Overall Number of Baseline Participants 171 92 263
Hide Baseline Analysis Population Description
A single participant in the Azithromycin group did not have baseline symptom information.
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 171 participants 92 participants 263 participants
42
(35 to 49)
44
(35 to 51)
43
(35 to 50)
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 168 participants 92 participants 260 participants
Female
117
  69.6%
57
  62.0%
174
  66.9%
Male
51
  30.4%
35
  38.0%
86
  33.1%
[1]
Measure Analysis Population Description: 3 participants did not provide their gender information
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Non-Hispanic White Number Analyzed 171 participants 92 participants 263 participants
94
  55.0%
56
  60.9%
150
  57.0%
Latinx/Hispanic Number Analyzed 171 participants 92 participants 263 participants
49
  28.7%
27
  29.3%
76
  28.9%
Non-Hispanic Black Number Analyzed 171 participants 92 participants 263 participants
11
   6.4%
1
   1.1%
12
   4.6%
Non-Hispanic Asian Number Analyzed 171 participants 92 participants 263 participants
6
   3.5%
3
   3.3%
9
   3.4%
Mixed Race Number Analyzed 171 participants 92 participants 263 participants
4
   2.3%
3
   3.3%
7
   2.7%
Non-Hispanic Middle Eastern/Arab Number Analyzed 171 participants 92 participants 263 participants
2
   1.2%
1
   1.1%
3
   1.1%
Prefer not to answer Number Analyzed 171 participants 92 participants 263 participants
1
   0.6%
0
   0.0%
1
   0.4%
Not reported (missing) Number Analyzed 171 participants 92 participants 263 participants
4
   2.3%
0
   0.0%
4
   1.5%
Non-Hispanic Native American Number Analyzed 171 participants 92 participants 263 participants
0
   0.0%
1
   1.1%
1
   0.4%
Geographic region  
Measure Type: Count of Participants
Unit of measure:  Participants
West Number Analyzed 171 participants 92 participants 263 participants
79
  46.2%
40
  43.5%
119
  45.2%
Southeast Number Analyzed 171 participants 92 participants 263 participants
38
  22.2%
14
  15.2%
52
  19.8%
Southwest Number Analyzed 171 participants 92 participants 263 participants
24
  14.0%
16
  17.4%
40
  15.2%
Midwest Number Analyzed 171 participants 92 participants 263 participants
21
  12.3%
16
  17.4%
37
  14.1%
Northeast Number Analyzed 171 participants 92 participants 263 participants
9
   5.3%
6
   6.5%
15
   5.7%
Alcohol consumption >3x/week  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 171 participants 92 participants 263 participants
23
  13.5%
9
   9.8%
32
  12.2%
Current cigarette smoker  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 171 participants 92 participants 263 participants
13
   7.6%
5
   5.4%
18
   6.8%
Current marijuana user  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 171 participants 92 participants 263 participants
9
   5.3%
6
   6.5%
15
   5.7%
Current e-cigarette/vaping  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 171 participants 92 participants 263 participants
8
   4.7%
2
   2.2%
10
   3.8%
Current cigar use  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 171 participants 92 participants 263 participants
1
   0.6%
1
   1.1%
2
   0.8%
Comorbidities  
Measure Type: Count of Participants
Unit of measure:  Participants
Asthma Number Analyzed 171 participants 92 participants 263 participants
21
  12.3%
11
  12.0%
32
  12.2%
Hypertension Number Analyzed 171 participants 92 participants 263 participants
20
  11.7%
12
  13.0%
32
  12.2%
Diabetes Number Analyzed 171 participants 92 participants 263 participants
5
   2.9%
5
   5.4%
10
   3.8%
Chronic obstructive pulmonary disease Number Analyzed 171 participants 92 participants 263 participants
4
   2.3%
0
   0.0%
4
   1.5%
Chronic kidney disease Number Analyzed 171 participants 92 participants 263 participants
1
   0.6%
1
   1.1%
2
   0.8%
Cancer Number Analyzed 171 participants 92 participants 263 participants
1
   0.6%
0
   0.0%
1
   0.4%
Stroke Number Analyzed 171 participants 92 participants 263 participants
1
   0.6%
1
   1.1%
2
   0.8%
Recent macrolide use (<30 days)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 171 participants 92 participants 263 participants
22
  12.9%
11
  12.0%
33
  12.5%
Recent hydroxychloroquine use (<7 days)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 171 participants 92 participants 263 participants
1
   0.6%
0
   0.0%
1
   0.4%
Current medications  
Measure Type: Count of Participants
Unit of measure:  Participants
ACE/ARB inhibitor Number Analyzed 171 participants 92 participants 263 participants
15
   8.8%
14
  15.2%
29
  11.0%
Metformin Number Analyzed 171 participants 92 participants 263 participants
4
   2.3%
3
   3.3%
7
   2.7%
Omeprazole Number Analyzed 171 participants 92 participants 263 participants
1
   0.6%
1
   1.1%
2
   0.8%
Tacrolimus Number Analyzed 171 participants 92 participants 263 participants
1
   0.6%
0
   0.0%
1
   0.4%
Current vitamin/supplement use  
Measure Type: Count of Participants
Unit of measure:  Participants
Vitamin D Number Analyzed 171 participants 92 participants 263 participants
64
  37.4%
37
  40.2%
101
  38.4%
Vitamin C Number Analyzed 171 participants 92 participants 263 participants
61
  35.7%
33
  35.9%
94
  35.7%
Multivitamin Number Analyzed 171 participants 92 participants 263 participants
52
  30.4%
27
  29.3%
79
  30.0%
Zinc Number Analyzed 171 participants 92 participants 263 participants
49
  28.7%
20
  21.7%
69
  26.2%
Omega-3 fatty acid Number Analyzed 171 participants 92 participants 263 participants
14
   8.2%
6
   6.5%
20
   7.6%
Self-reported symptoms  
Measure Type: Count of Participants
Unit of measure:  Participants
Multiple symptoms Number Analyzed 171 participants 92 participants 263 participants
152
  88.9%
82
  89.1%
234
  89.0%
Cough Number Analyzed 171 participants 92 participants 263 participants
111
  64.9%
61
  66.3%
172
  65.4%
Fatigue Number Analyzed 171 participants 92 participants 263 participants
107
  62.6%
55
  59.8%
162
  61.6%
Fever Number Analyzed 171 participants 92 participants 263 participants
87
  50.9%
40
  43.5%
127
  48.3%
Myalgia Number Analyzed 171 participants 92 participants 263 participants
82
  48.0%
40
  43.5%
122
  46.4%
Anosmia Number Analyzed 171 participants 92 participants 263 participants
80
  46.8%
39
  42.4%
119
  45.2%
Sore throat Number Analyzed 171 participants 92 participants 263 participants
71
  41.5%
37
  40.2%
108
  41.1%
Diarrhea Number Analyzed 171 participants 92 participants 263 participants
45
  26.3%
20
  21.7%
65
  24.7%
Shortness of breath Number Analyzed 171 participants 92 participants 263 participants
45
  26.3%
17
  18.5%
62
  23.6%
Dizziness Number Analyzed 171 participants 92 participants 263 participants
39
  22.8%
15
  16.3%
54
  20.5%
Abdominal pain Number Analyzed 171 participants 92 participants 263 participants
29
  17.0%
12
  13.0%
41
  15.6%
None Number Analyzed 171 participants 92 participants 263 participants
12
   7.0%
6
   6.5%
18
   6.8%
Conjunctivitis Number Analyzed 171 participants 92 participants 263 participants
8
   4.7%
2
   2.2%
10
   3.8%
Number of symptoms  
Median (Inter-Quartile Range)
Unit of measure:  Number of symptoms
Number Analyzed 171 participants 92 participants 263 participants
5
(3 to 6)
4
(3 to 6)
4
(3 to 6)
Duration of symptoms prior to test  
Median (Inter-Quartile Range)
Unit of measure:  Days
Number Analyzed 171 participants 92 participants 263 participants
3
(2 to 4.5)
3
(2 to 4)
3
(2 to 4)
Days between positive test and enrollment  
Median (Inter-Quartile Range)
Unit of measure:  Days
Number Analyzed 171 participants 92 participants 263 participants
3
(1 to 5)
2
(1 to 4)
3
(1 to 5)
1.Primary Outcome
Title Number of Participants Who Were Symptom Free at Day 14
Hide Description Binary assessment of whether the participant is experiencing any symptoms at Day 14 (yes or no)
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
Percentage of participants who were symptom free at day 14 by randomized treatment group, overall and in pre-specified subgroups. Note that a single participant in the Azithromycin group did not have baseline symptom information.
Arm/Group Title Azithromycin Placebo
Hide Arm/Group Description:

1.2g of oral azithromycin

Azithromycin: Participants will be shipped a single 1.2 g dose of oral azithromycin

Matching placebo

Placebos: Participants will be shipped a dose of matching placebo

Overall Number of Participants Analyzed 131 70
Measure Type: Count of Participants
Unit of Measure: Participants
Overall Number Analyzed 131 participants 70 participants
66
  50.4%
35
  50.0%
Age <= 60 years Number Analyzed 121 participants 62 participants
61
  50.4%
31
  50.0%
Age > 60 years Number Analyzed 10 participants 8 participants
5
  50.0%
4
  50.0%
Asymptomatic at baseline Number Analyzed 10 participants 4 participants
9
  90.0%
3
  75.0%
Symptomatic at baseline Number Analyzed 120 participants 66 participants
57
  47.5%
32
  48.5%
2.Secondary Outcome
Title Viral Load
Hide Description Viral load by self-collected nasal swab
Time Frame 3 days
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Viral Load
Hide Description Viral load by self-collected saliva swab
Time Frame 3 days
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Mortality
Hide Description All-cause mortality
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
This outcome is based on the 125 participants in the azithromycin group and the 72 participants in the placebo group who completed the trial.
Arm/Group Title Azithromycin Placebo
Hide Arm/Group Description:

1.2g of oral azithromycin

Azithromycin: Participants will be shipped a single 1.2 g dose of oral azithromycin

Matching placebo

Placebos: Participants will be shipped a dose of matching placebo

Overall Number of Participants Analyzed 125 72
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
5.Secondary Outcome
Title Adverse Events
Hide Description Percentage of participants experiencing adverse events, including gastrointestinal side effects and rash
Time Frame 3 days
Hide Outcome Measure Data
Hide Analysis Population Description
Adverse events were recorded at day 3 of the trial via an online questionnaire. Other adverse events were recorded in an open text field and included stomach cramps, light headedness, fatigue, ansomia, cough, and painful respiration.
Arm/Group Title Azithromycin Placebo
Hide Arm/Group Description:

1.2g of oral azithromycin

Azithromycin: Participants will be shipped a single 1.2 g dose of oral azithromycin

Matching placebo

Placebos: Participants will be shipped a dose of matching placebo

Overall Number of Participants Analyzed 145 72
Measure Type: Count of Participants
Unit of Measure: Participants
Diarrhea
60
  41.4%
12
  16.7%
Nausea
32
  22.1%
7
   9.7%
Abdominal Pain
25
  17.2%
1
   1.4%
Vomiting
5
   3.4%
2
   2.8%
Rash
4
   2.8%
2
   2.8%
Other
10
   6.9%
3
   4.2%
None
9
   6.2%
45
  62.5%
6.Secondary Outcome
Title Positive SARS-CoV-2 Test - Nasal Swab
Hide Description Prevalence of positive SARS-CoV-2 test by self-collected nasal swab
Time Frame 3 days
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Positive SARS-CoV-2 Test - Saliva Swab
Hide Description Prevalence of positive SARS-CoV-2 test by self-collected saliva swab
Time Frame 3 days
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Positive SARS-CoV-2 Test - Rectal Swab
Hide Description Prevalence of positive SARS-CoV-2 test by self-collected rectal swab
Time Frame 3 days
Outcome Measure Data Not Reported
9.Secondary Outcome
Title Genetic Macrolide Resistance Determinants
Hide Description Prevalence of genetic macrolide resistance determinants by self-collected rectal swab
Time Frame 3 days
Outcome Measure Data Not Reported
10.Secondary Outcome
Title Secondary Outcomes Through Day 21
Hide Description Prevalence of cough, fever, myalgia, anosmia, shortness of breath, fatigue, conjunctivitis, and orthostatic symptoms through Day 21
Time Frame Cumulative over 21 days reported (assessed at 3, 7, 14, 21 days)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Azithromycin Placebo
Hide Arm/Group Description:

1.2g of oral azithromycin

Azithromycin: Participants will be shipped a single 1.2 g dose of oral azithromycin

Matching placebo

Placebos: Participants will be shipped a dose of matching placebo

Overall Number of Participants Analyzed 125 72
Measure Type: Count of Participants
Unit of Measure: Participants
Absence of symptoms
71
  56.8%
43
  59.7%
Fever
1
   0.8%
1
   1.4%
Cough
14
  11.2%
13
  18.1%
Diarrhea
4
   3.2%
1
   1.4%
Abdominal pain
0
   0.0%
1
   1.4%
Anosmia
12
   9.6%
9
  12.5%
Conjunctivitis
2
   1.6%
0
   0.0%
Sore throat
4
   3.2%
4
   5.6%
Shortness of breath
16
  12.8%
4
   5.6%
Myalgia
5
   4.0%
3
   4.2%
Fatigue
32
  25.6%
17
  23.6%
Dizziness
6
   4.8%
3
   4.2%
Other
10
   8.0%
9
  12.5%
11.Secondary Outcome
Title Number of Participants With Emergency Room Visits
Hide Description Number of emergency room visits <24 hours
Time Frame 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
Number of patients who reported emergency room visit information through Day 21
Arm/Group Title Azithromycin Placebo
Hide Arm/Group Description:

1.2g of oral azithromycin

Azithromycin: Participants will be shipped a single 1.2 g dose of oral azithromycin

Matching placebo

Placebos: Participants will be shipped a dose of matching placebo

Overall Number of Participants Analyzed 125 72
Measure Type: Count of Participants
Unit of Measure: Participants
18
  14.4%
2
   2.8%
12.Secondary Outcome
Title Number of Household Members With COVID-19 (Confirmed or Symptomatic)
Hide Description Number of household members with confirmed or symptomatic COVID-19 through Day 21
Time Frame 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
Includes the total number of participants from 69 households in the placebo group and 134 households in the azithromycin group
Arm/Group Title Azithromycin Placebo
Hide Arm/Group Description:

1.2g of oral azithromycin

Azithromycin: Participants will be shipped a single 1.2 g dose of oral azithromycin

Matching placebo

Placebos: Participants will be shipped a dose of matching placebo

Overall Number of Participants Analyzed 522 278
Measure Type: Count of Participants
Unit of Measure: Participants
33
   6.3%
20
   7.2%
13.Secondary Outcome
Title Number of Participants That Died
Hide Description Deaths within the study
Time Frame 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants that completed the day 21 questionnaire were included in this secondary analysis.
Arm/Group Title Azithromycin Placebo
Hide Arm/Group Description:

1.2g of oral azithromycin

Azithromycin: Participants will be shipped a single 1.2 g dose of oral azithromycin

Matching placebo

Placebos: Participants will be shipped a dose of matching placebo

Overall Number of Participants Analyzed 125 72
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
14.Secondary Outcome
Title Number of Participants Reporting Hospitalization
Hide Description Number of hospitalizations defined as a hospital stay or ER stay longer than 24 hours through 21 days post enrollment
Time Frame 21 Days
Hide Outcome Measure Data
Hide Analysis Population Description
Number of patients who reported hospitalization information through Day 21
Arm/Group Title Azithromycin Placebo
Hide Arm/Group Description:

1.2g of oral azithromycin

Azithromycin: Participants will be shipped a single 1.2 g dose of oral azithromycin

Matching placebo

Placebos: Participants will be shipped a dose of matching placebo

Overall Number of Participants Analyzed 125 72
Measure Type: Count of Participants
Unit of Measure: Participants
5
   4.0%
0
   0.0%
Time Frame 21 days
Adverse Event Reporting Description Participants completed a survey at day 3 where they were asked if they had experienced any of the following symptoms since they took their study medication to assess possible adverse events: vomiting, nausea, diarrhea, rash, or abdominal pain. Participants were asked at every time point if they had stayed in a hospital setting (defined as in the emergency department or admitted to the hospital for >= 24 hours) and/or if they had visited an emergency department or urgent care center.
 
Arm/Group Title Azithromycin Placebo
Hide Arm/Group Description

1.2g of oral azithromycin

Azithromycin: Participants will be shipped a single 1.2 g dose of oral azithromycin

Matching placebo

Placebos: Participants will be shipped a dose of matching placebo

All-Cause Mortality
Azithromycin Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/145 (0.00%)   0/72 (0.00%) 
Hide Serious Adverse Events
Azithromycin Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/145 (0.00%)   0/72 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Azithromycin Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   132/145 (91.03%)   25/72 (34.72%) 
Gastrointestinal disorders     
Diarrhea   60/145 (41.38%)  12/72 (16.67%) 
Nausea   32/145 (22.07%)  7/72 (9.72%) 
Abdominal pain   25/145 (17.24%)  1/72 (1.39%) 
Vomiting   5/145 (3.45%)  2/72 (2.78%) 
Other   10/145 (6.90%)  3/72 (4.17%) 
Indicates events were collected by systematic assessment

This trial was terminated early by the DSMC for futility on March 16, 2021. Therefore, we were not able to complete the analysis for all secondary outcomes because funds were returned to the sponsor following the completion of the study.

Please note that the number of participants varies by period as participants could opt to complete some questionnaires but not others. For example, a participant may skip the day 3 questionnaire, but complete the day 14 questionnaire.

Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Thomas Lietman, Director of the UCSF FI Proctor Foundation
Organization: University of California, San Francisco FI Proctor Foundation
Phone: 415-476-1442
EMail: tom.lietman@ucsf.edu
Layout table for additonal information
Responsible Party: Thomas M. Lietman, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT04332107    
Other Study ID Numbers: 20-30504
First Submitted: March 30, 2020
First Posted: April 2, 2020
Results First Submitted: August 9, 2021
Results First Posted: September 9, 2021
Last Update Posted: October 7, 2021