Trial Outcomes & Findings for AZithromycin Therapy in Preschoolers With a Severe Wheezing Episode Diagnosed at the Emergency Department (NCT NCT04669288)
NCT ID: NCT04669288
Last Updated: 2026-06-23
Results Overview
The Asthma Flare-up Diary for Young Children (ADYC) is a validated instrument that consists of a 17-item questionnaire scored from 1 (best) to 7 (worst). The parent or guardian of the enrolled child (up to 60 months of age) filled out the diary daily for 5 days, starting from the first day following the first dose of Azithromycin (AZ). The cumulative score at the end of 5 days was used to assess response to the intervention (e.g. time to exacerbation, acute-care visit, hospitalization and no wheeze), with a higher score indicating a worse outcome. For each of the five follow-up days, the ADYC score was calculated as the average score per question and the trial primary outcome was the sum of these ADYC scores over the five days. The range of possible primary outcome values was a ADYC score of 5 to 35.
TERMINATED
PHASE3
840 participants
5 day course of azithromycin
2026-06-23
Participant Flow
Patients aged 18 to 59 months of age and presenting in the emergency department with an episode of wheezing that was moderate/severe by clinical score (PRAM score of greater than or equal to 4). The first participant was enrolled 22-November-2021. The last participant was enrolled 10-December-2024 when enrollment was stopped by the Data Safety Monitoring Board based interim analysis futility.
Of the 840 enrolled participants, 833 were randomized into one of the two study arms and were tested for pathogenic bacteria.
Participant milestones
| Measure |
Treatment - Active (Azithromycin)
Participants received 12 mg/kg dose per day of oral azithromycin for 5 days. The first dose of the study medication was administered before discharge from the ED. Remaining study azithromycin was given to parents to administer at home for 4 subsequent days. Azithromycin oral suspension
|
Treatment - Placebo
Participants received 12 mg/kg dose per day of oral placebo for 5 days. The first dose of the study azithromycin-placebo liquid was administered orally before discharge from the ED. Remaining azithromycin-placebo was given to parents to administer at home for 4 subsequent days. Placebo: Azithromycin placebo, oral suspension.
|
|---|---|---|
|
Overall Study
STARTED
|
415
|
418
|
|
Overall Study
Bacterial
|
257
|
264
|
|
Overall Study
Non-Bacterial
|
158
|
154
|
|
Overall Study
COMPLETED
|
408
|
404
|
|
Overall Study
NOT COMPLETED
|
7
|
14
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Subjects are separated by treatment arm and by bacterial designation. Together, the rows equal the total number of participants analyzed.
Baseline characteristics by cohort
| Measure |
Treatment - Active (Azithromycin)
n=413 NP Swab Positive Viruses
Aged 18-60 months of age (mo). Separated by positive for bacterial infection and negative for bacterial infection.
|
Treatment - Placebo
n=417 NP Swab Positive Viruses
Aged 18-60 months of age (mo). Separated by positive for bacterial infection and negative for bacterial infection.
|
Total
n=830 NP Swab Positive Viruses
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
18 to <24 Months
|
62 Participants
n=415 Participants
|
80 Participants
n=418 Participants
|
142 Participants
n=833 Participants
|
|
Age, Customized
24 to <36 Months
|
142 Participants
n=415 Participants
|
135 Participants
n=418 Participants
|
277 Participants
n=833 Participants
|
|
Age, Customized
36 to <48 Months
|
123 Participants
n=415 Participants
|
117 Participants
n=418 Participants
|
240 Participants
n=833 Participants
|
|
Age, Customized
48 to <60 Months
|
88 Participants
n=415 Participants
|
86 Participants
n=418 Participants
|
174 Participants
n=833 Participants
|
|
Sex: Female, Male
Female
|
158 Participants
n=415 Participants
|
163 Participants
n=418 Participants
|
321 Participants
n=833 Participants
|
|
Sex: Female, Male
Male
|
257 Participants
n=415 Participants
|
255 Participants
n=418 Participants
|
512 Participants
n=833 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=415 Participants
|
1 Participants
n=418 Participants
|
3 Participants
n=833 Participants
|
|
Race (NIH/OMB)
Asian
|
7 Participants
n=415 Participants
|
5 Participants
n=418 Participants
|
12 Participants
n=833 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
193 Participants
n=415 Participants
|
204 Participants
n=418 Participants
|
397 Participants
n=833 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=415 Participants
|
0 Participants
n=418 Participants
|
2 Participants
n=833 Participants
|
|
Race (NIH/OMB)
White
|
142 Participants
n=415 Participants
|
138 Participants
n=418 Participants
|
280 Participants
n=833 Participants
|
|
Race (NIH/OMB)
More than one race
|
22 Participants
n=415 Participants
|
20 Participants
n=418 Participants
|
42 Participants
n=833 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
47 Participants
n=415 Participants
|
50 Participants
n=418 Participants
|
97 Participants
n=833 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
77 Participants
n=415 Participants
|
88 Participants
n=418 Participants
|
165 Participants
n=833 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
330 Participants
n=415 Participants
|
322 Participants
n=418 Participants
|
652 Participants
n=833 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
8 Participants
n=415 Participants
|
8 Participants
n=418 Participants
|
16 Participants
n=833 Participants
|
|
Hospitalization
Hospitalized
|
200 Participants
n=415 Participants
|
216 Participants
n=418 Participants
|
416 Participants
n=833 Participants
|
|
Hospitalization
Not Hospitalized
|
215 Participants
n=415 Participants
|
202 Participants
n=418 Participants
|
417 Participants
n=833 Participants
|
|
Antibiotics in the ED
Subject took other antibiotics in the ED
|
7 Participants
n=415 Participants
|
5 Participants
n=418 Participants
|
12 Participants
n=833 Participants
|
|
Antibiotics in the ED
No other antibiotics taken in ED
|
408 Participants
n=415 Participants
|
413 Participants
n=418 Participants
|
821 Participants
n=833 Participants
|
|
Pediatric Respiratory Assessment Measure (PRAM)
Bacterial
|
6.0 scored on a range
STANDARD_DEVIATION 1.78 • n=257 Participants • Subjects are separated by treatment arm and by bacterial designation. Together, the rows equal the total number of participants analyzed.
|
6.2 scored on a range
STANDARD_DEVIATION 1.81 • n=264 Participants • Subjects are separated by treatment arm and by bacterial designation. Together, the rows equal the total number of participants analyzed.
|
6.1 scored on a range
STANDARD_DEVIATION 1.80 • n=521 Participants • Subjects are separated by treatment arm and by bacterial designation. Together, the rows equal the total number of participants analyzed.
|
|
Pediatric Respiratory Assessment Measure (PRAM)
Non-Bacterial
|
6.5 scored on a range
STANDARD_DEVIATION 1.91 • n=158 Participants • Subjects are separated by treatment arm and by bacterial designation. Together, the rows equal the total number of participants analyzed.
|
6.6 scored on a range
STANDARD_DEVIATION 1.97 • n=154 Participants • Subjects are separated by treatment arm and by bacterial designation. Together, the rows equal the total number of participants analyzed.
|
6.5 scored on a range
STANDARD_DEVIATION 1.94 • n=312 Participants • Subjects are separated by treatment arm and by bacterial designation. Together, the rows equal the total number of participants analyzed.
|
|
PRAM Score By Range
PRAM Score Range: 5-7
|
318 Participants
n=415 Participants
|
319 Participants
n=418 Participants
|
637 Participants
n=833 Participants
|
|
PRAM Score By Range
PRAM Score Range: 8-12
|
97 Participants
n=415 Participants
|
99 Participants
n=418 Participants
|
196 Participants
n=833 Participants
|
|
NP Swab Viral Results
Viral Positive
|
352 Participants
n=415 Participants
|
365 Participants
n=418 Participants
|
717 Participants
n=833 Participants
|
|
NP Swab Viral Results
Viral Negative
|
63 Participants
n=415 Participants
|
53 Participants
n=418 Participants
|
116 Participants
n=833 Participants
|
|
NP Swab Positive for Viruses
Human Rhinovirus (HRV) Results
|
292 NP Swab Positive Viruses
n=413 NP Swab Positive Viruses
|
312 NP Swab Positive Viruses
n=417 NP Swab Positive Viruses
|
604 NP Swab Positive Viruses
n=830 NP Swab Positive Viruses
|
|
NP Swab Positive for Viruses
Human Respiratory Syncytial Virus (RSV) Results
|
37 NP Swab Positive Viruses
n=413 NP Swab Positive Viruses
|
40 NP Swab Positive Viruses
n=417 NP Swab Positive Viruses
|
77 NP Swab Positive Viruses
n=830 NP Swab Positive Viruses
|
|
NP Swab Positive for Viruses
Bocavirus (HBoV) Results
|
24 NP Swab Positive Viruses
n=413 NP Swab Positive Viruses
|
14 NP Swab Positive Viruses
n=417 NP Swab Positive Viruses
|
38 NP Swab Positive Viruses
n=830 NP Swab Positive Viruses
|
|
NP Swab Positive for Viruses
Human Metapneumovirus (hMPV) Results
|
20 NP Swab Positive Viruses
n=413 NP Swab Positive Viruses
|
11 NP Swab Positive Viruses
n=417 NP Swab Positive Viruses
|
31 NP Swab Positive Viruses
n=830 NP Swab Positive Viruses
|
|
NP Swab Positive for Viruses
Human Parainfluenza (HPIV) Results
|
11 NP Swab Positive Viruses
n=413 NP Swab Positive Viruses
|
13 NP Swab Positive Viruses
n=417 NP Swab Positive Viruses
|
24 NP Swab Positive Viruses
n=830 NP Swab Positive Viruses
|
|
NP Swab Positive for Viruses
Any other combination of viruses (Other) Results
|
29 NP Swab Positive Viruses
n=413 NP Swab Positive Viruses
|
27 NP Swab Positive Viruses
n=417 NP Swab Positive Viruses
|
56 NP Swab Positive Viruses
n=830 NP Swab Positive Viruses
|
PRIMARY outcome
Timeframe: 5 day course of azithromycinPopulation: ADYC surveys were completed for assessment using imputation
The Asthma Flare-up Diary for Young Children (ADYC) is a validated instrument that consists of a 17-item questionnaire scored from 1 (best) to 7 (worst). The parent or guardian of the enrolled child (up to 60 months of age) filled out the diary daily for 5 days, starting from the first day following the first dose of Azithromycin (AZ). The cumulative score at the end of 5 days was used to assess response to the intervention (e.g. time to exacerbation, acute-care visit, hospitalization and no wheeze), with a higher score indicating a worse outcome. For each of the five follow-up days, the ADYC score was calculated as the average score per question and the trial primary outcome was the sum of these ADYC scores over the five days. The range of possible primary outcome values was a ADYC score of 5 to 35.
Outcome measures
| Measure |
Treatment: Placebo
n=418 Participants
Eligible participants who were hospitalized during treatment
|
Treatment: Azithromycin
n=415 Participants
Eligible participants who returned to the ED or were hospitalized within 72 hours following randomization
|
|---|---|---|
|
ADYC (Median, IQR)
Non-Bacterial
|
9.10 Scored on a scale
Interval 7.19 to 11.45
|
9.30 Scored on a scale
Interval 6.97 to 11.62
|
|
ADYC (Median, IQR)
Bacterial
|
9.72 Scored on a scale
Interval 7.66 to 12.17
|
9.59 Scored on a scale
Interval 7.29 to 12.6
|
SECONDARY outcome
Timeframe: From admission at ED to discharge from ED, up to 23 hours and 59 minutesPopulation: The Length of Stay (LOS) measurement is assessed on all 833 participants randomized in the ED
The continuous secondary variable of length of stay was analyzed in the same manner as the primary outcome. The measurement is the duration from arrival to ED to discharge. Subjects are separated by treatment arm and by bacterial designation. Together, the rows equal the total number of participants analyzed.
Outcome measures
| Measure |
Treatment: Placebo
n=418 Participants
Eligible participants who were hospitalized during treatment
|
Treatment: Azithromycin
n=415 Participants
Eligible participants who returned to the ED or were hospitalized within 72 hours following randomization
|
|---|---|---|
|
ED Length of Stay (Median, IQR)
Bacterial
|
4.9 Hours of stay at the ED
Interval 3.9 to 7.0
|
5.2 Hours of stay at the ED
Interval 4.1 to 6.8
|
|
ED Length of Stay (Median, IQR)
Non-Bacterial
|
4.9 Hours of stay at the ED
Interval 3.8 to 6.4
|
4.9 Hours of stay at the ED
Interval 3.9 to 6.2
|
SECONDARY outcome
Timeframe: From hospital admission to discharge from hospitalPopulation: Length of hospitalization in hours was measured in all children. One patient, from the Placebo-Bacterial group had missing length of stay.
The continuous secondary variable of length of stay was analyzed in the same manner as the primary outcome. The measurement is the duration of hospitalization from admission. Subjects are separated by treatment arm and by bacterial designation. Together, the rows equal the total number of participants analyzed.
Outcome measures
| Measure |
Treatment: Placebo
n=418 Participants
Eligible participants who were hospitalized during treatment
|
Treatment: Azithromycin
n=415 Participants
Eligible participants who returned to the ED or were hospitalized within 72 hours following randomization
|
|---|---|---|
|
Hospital Length of Stay (Median, IQR)
Bacterial
|
15.8 Hours of stay after hospitalization
Interval 4.3 to 29.6
|
7.7 Hours of stay after hospitalization
Interval 4.5 to 28.4
|
|
Hospital Length of Stay (Median, IQR)
Non-Bacterial
|
16.9 Hours of stay after hospitalization
Interval 4.3 to 29.5
|
13.1 Hours of stay after hospitalization
Interval 4.3 to 29.5
|
SECONDARY outcome
Timeframe: Within 72 hours after randomizationPopulation: Subjects are separated by treatment arm and by bacterial designation. Together, the rows equal the total number of participants analyzed.
Visits to the ED or hospital within 72 hours of the initial visit (randomization time) are counted as a revisit outcome. This outcome was tabulated by treatment for each stratum (site and baseline severity of symptoms). The dichotomous outcome of the second ED visit or hospitalization is compared using a Mantel-Haenszel chi-square test, stratified by clinical center and baseline severity.
Outcome measures
| Measure |
Treatment: Placebo
n=418 Participants
Eligible participants who were hospitalized during treatment
|
Treatment: Azithromycin
n=415 Participants
Eligible participants who returned to the ED or were hospitalized within 72 hours following randomization
|
|---|---|---|
|
Return Visit
Bacterial
|
5 Visits
Standard Deviation 1.89
|
3 Visits
Standard Deviation 1.17
|
|
Return Visit
Non-Bacterial
|
2 Visits
Standard Deviation 1.31
|
2 Visits
Standard Deviation 1.27
|
Adverse Events
Treatment - Active (Azithromycin)
Treatment - Placebo
Serious adverse events
| Measure |
Treatment - Active (Azithromycin)
n=415 participants at risk
In the azithromycin arm serious adverse events included respiratory distress, bronchospasm, increased work of breathing, respiratory failure, septic shock, and severe cough.
|
Treatment - Placebo
n=418 participants at risk
In the placebo arm serious adverse events included respiratory distress, respiratory failure, bronchospasm, increased work of breathing, severe cough, and septic shock.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Distress
|
0.72%
3/415 • From enrollment until the end of follow-up, up to 21 days
|
0.48%
2/418 • From enrollment until the end of follow-up, up to 21 days
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
0.24%
1/415 • From enrollment until the end of follow-up, up to 21 days
|
0.00%
0/418 • From enrollment until the end of follow-up, up to 21 days
|
|
Respiratory, thoracic and mediastinal disorders
Increased Work of Breathing
|
0.00%
0/415 • From enrollment until the end of follow-up, up to 21 days
|
0.48%
2/418 • From enrollment until the end of follow-up, up to 21 days
|
|
Respiratory, thoracic and mediastinal disorders
RSV Infection
|
0.00%
0/415 • From enrollment until the end of follow-up, up to 21 days
|
0.24%
1/418 • From enrollment until the end of follow-up, up to 21 days
|
|
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure
|
0.24%
1/415 • From enrollment until the end of follow-up, up to 21 days
|
0.00%
0/418 • From enrollment until the end of follow-up, up to 21 days
|
|
Infections and infestations
Septic Shock
|
0.24%
1/415 • From enrollment until the end of follow-up, up to 21 days
|
0.00%
0/418 • From enrollment until the end of follow-up, up to 21 days
|
|
Respiratory, thoracic and mediastinal disorders
Hypercapnic Respiratory Failure
|
0.24%
1/415 • From enrollment until the end of follow-up, up to 21 days
|
0.00%
0/418 • From enrollment until the end of follow-up, up to 21 days
|
|
Respiratory, thoracic and mediastinal disorders
Cough Increased
|
0.00%
0/415 • From enrollment until the end of follow-up, up to 21 days
|
0.24%
1/418 • From enrollment until the end of follow-up, up to 21 days
|
Other adverse events
| Measure |
Treatment - Active (Azithromycin)
n=415 participants at risk
In the azithromycin arm serious adverse events included respiratory distress, bronchospasm, increased work of breathing, respiratory failure, septic shock, and severe cough.
|
Treatment - Placebo
n=418 participants at risk
In the placebo arm serious adverse events included respiratory distress, respiratory failure, bronchospasm, increased work of breathing, severe cough, and septic shock.
|
|---|---|---|
|
Immune system disorders
S pneumonia Resistant at Baseline
|
28.9%
13/45 • From enrollment until the end of follow-up, up to 21 days
|
41.0%
16/39 • From enrollment until the end of follow-up, up to 21 days
|
|
Immune system disorders
S pneumonia Resistant at Followup
|
21.9%
7/32 • From enrollment until the end of follow-up, up to 21 days
|
8.7%
2/23 • From enrollment until the end of follow-up, up to 21 days
|
|
Immune system disorders
Safety Outcome: Bacterial Resistant at baseline (subsample n=209)
|
23.9%
99/415 • From enrollment until the end of follow-up, up to 21 days
|
26.3%
110/418 • From enrollment until the end of follow-up, up to 21 days
|
|
Immune system disorders
Bacterial Resistant at Baseline
|
16.2%
16/99 • From enrollment until the end of follow-up, up to 21 days
|
17.3%
19/110 • From enrollment until the end of follow-up, up to 21 days
|
|
Immune system disorders
Bacterial Resistant at Followup
|
21.7%
18/83 • From enrollment until the end of follow-up, up to 21 days
|
22.0%
20/91 • From enrollment until the end of follow-up, up to 21 days
|
|
Immune system disorders
H Influenzae Resistant at Baseline
|
0.00%
0/28 • From enrollment until the end of follow-up, up to 21 days
|
4.8%
1/21 • From enrollment until the end of follow-up, up to 21 days
|
|
Immune system disorders
H Influenzae Resistant at Followup
|
7.1%
2/28 • From enrollment until the end of follow-up, up to 21 days
|
0.00%
0/20 • From enrollment until the end of follow-up, up to 21 days
|
|
Immune system disorders
M catarrhalis Resistant at Baseline
|
5.4%
4/74 • From enrollment until the end of follow-up, up to 21 days
|
3.5%
3/86 • From enrollment until the end of follow-up, up to 21 days
|
|
Immune system disorders
M catarrahlis Resistant at Followup
|
1.4%
1/70 • From enrollment until the end of follow-up, up to 21 days
|
2.4%
2/83 • From enrollment until the end of follow-up, up to 21 days
|
Additional Information
Fernando D. Martinez, MD
Arizona Board of Regents, University of Arizona
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place