AsthmaPhase 3AZ-SWEDNCT04669288
AZithromycin Therapy in Preschoolers With a Severe Wheezing Episode Diagnosed at the Emergency Department
A Phase 3 study testing Azithromycin in people with Asthma and Wheezing, run by University of Arizona at 8 sites in United States.
Trial summary
AZ-SWED is a parallel group, double blind, placebo control efficacy clinical trial with two separate hypotheses. The trial compared the 5-day outcome of preschool children presenting to an Emergency Department (ED) with an acute, severe wheezing episode and treated with either once daily oral Azithromycin (12… Read more about this study
- Who is it for?
- Ages 18 to 60 months
- What is being tested?
- Azithromycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 840 participants
- Where
- 8 sitesUnited States
- Study dates
- 22 Nov 2021to 8 Jan 2025
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age 18 months to <60 months.
- The presence of expiratory wheezing as ascertained by a physician or nurse practitioner at admission to the ED.
- A Pediatric Respiratory Assessment Measurement (PRAM) score of greater than or equal to 4 at any time during the ED admission.
Who cannot join
- Presence of acute infection that requires systemic antibiotics, as determined by the physician.
- Current or previous use of systemic antibiotics within the last 2 weeks.
- Current or previous use of a steroid for wheezing within the last 2 weeks.
- Suspected foreign body induced aspiration during the last 2 weeks.
- A known systemic illness (other than allergy) including but not limited to:
- Recurrent seizures
Show all 25Show fewer
- Gastroesophageal reflux (GER) requiring medical treatment
- Major congenital anomalies
- Physical and intellectual delay
- Cerebral palsy
- A history of chest surgery
- Tuberculosis or other chronic infections
- Primary or secondary immunodeficiency
- Gastrointestinal malformation or disease
- Cardiac disorder (except for a hemodynamically insignificant atrial septal defect (ASD), ventricular septal defect (VSD) or benign heart murmur)
- Born at less than 36 weeks estimated gestational age.
- Received oxygen for more than 5 days in the neonatal period, or received invasive mechanical ventilation.
- Significant developmental delay / failure to thrive, defined as a child plotting less than 3rd percentile.
- Any chronic lung disease.
- The study intervention poses undue risk to patient in the opinion of the treating physician
- Known sensitivity or allergy to AZ.
- Participation in the evaluation of a drug or medical device currently or within the last 30 days.
- Previous enrollment into this trial.
- Inability of the parent or guardian to speak English or Spanish.
- Positive PCR or antigen test for COVID-19 from hospital/doctor's office/testing center within the past 30 days.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Children's Healthcare of Atlanta, Emory University
Atlanta, Georgia, 30322
Boston Children's Hospital
Boston, Massachusetts, 02115
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
The Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Children's Hospital of New York Medical Center
New York, New York, 10032
The Children's Hospital of Philadelphia (CHOP)
Philadelphia, Pennsylvania, 19104
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
About this study
Official title: AZithromycin Therapy in Preschoolers With a Severe Wheezing Episode Diagnosed at the Emergency Department (AZ-SWED)
AZ-SWED is a parallel group, double blind, placebo control efficacy clinical trial with two separate hypotheses. The trial compared the 5-day outcome of preschool children presenting to an Emergency Department (ED) with an acute, severe wheezing episode and treated with either once daily oral Azithromycin (12 mg/kg/day for 5 days) or placebo. The AZ-SWED researchers made separate comparisons in children in whom specific pathogenic bacteria isolated from nasopharyngeal swabs, and in those in whom they were not isolated. The primary outcome was the Asthma Flare-up Diary for Young Children (ADYC), a validated instrument that caregivers will transmit electronically daily after discharge from the ED. Families were contacted daily during the five-day treatment to collect the ADYC, and to assess compliance and complications. A randomly chosen subset of enrolled children participated in two follow-up visits 5-8 days and 14-21 days after visit 1 to assess development of resistance to study drug and treatment response related changes in the airway microbiome.
Read the detailed description
This Phase III trial is designed as a parallel group, placebo-controlled, double-blind, randomized, multi-center evaluation of AZ for the treatment of acute wheezing episodes. The study recruited eligible patients from seven EDs. We tested two primary hypotheses: 1) AZ (12 mg/Kg/day) given for 5 days to preschool children with severe acute wheezing and harboring any of three specific pathogenic bacteria (H influenzae, M catarrhalis, or S pneumonia) in their nasopharynx will decrease the severity of the acute episode; and 2) AZ given on an identical schedule and dose will decrease the severity of wheezing episodes in children who do not harbor any of these three pathogenic bacteria in their nasopharynx.
This study had three visits. All enrolled patients participated on the Day 0 visit for screening, the informed consent process, enrollment, randomization, treatment initiation and dispensing drug. A sub-group of randomly selected patients participated in two follow-up visits on Day 5 - 8 and Day 14 - 21 where they were tested for antibiotic resistance.
The primary outcome was the sum of the Asthma Flare-up Diary for Young Children (ADYC) score, a validated instrument completed by the parent or guardian of the enrolled children during the 5-day treatment period. Secondary outcomes will include (1) ED length of stay (2) hospital length of stay, and (3) return ED visits or hospitalizations within 72 hours after randomization.
- Being tested
- Azithromycin, Placebo
- Keywords
- Wheezing Lower Respiratory Illness (WLRI)
- Medical subject headings
- Asthma, Respiratory Sounds
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzithromycinDrug
oral azithromycin (12 mg/kg per day for 5 days)
Local investigational drug pharmacies were provided with active study medication (azithromycin) from a central pharmacy. Azithromycin was reconstituted with water at the local pharmacy, and resembled placebo with regards to appearance, flavor, consistency and packaging.
PlaceboDrug
oral placebo (12 mg/kg per day for 5 days)
Local investigational drug pharmacies were provided with placebo from a central pharmacy. Placebo was reconstituted with water at the local pharmacy, and resembled azithromycin with regards to appearance, flavor, consistency and packaging.
| Study group | Role | What they receive |
|---|---|---|
| Treatment - Active | Active comparator | Eligible participants were randomly assigned to the Azithromycin arm (1:1) Receives: Drug: Azithromycin |
| Treatment - Placebo | Placebo comparator | Eligible patients were randomly assigned to the placebo arm, per the randomization schedule (1:1). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
ADYC (Median, IQR)
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.
Measured: 5 day course of azithromycin
Secondary outcomes (3)
ED Length of Stay (Median, IQR)
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.
Measured: From admission at ED to discharge from ED, up to 23 hours and 59 minutes
Hospital Length of Stay (Median, IQR)
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.
Measured: From hospital admission to discharge from hospital
Return Visit
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.
Measured: Within 72 hours after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2020
- Study start22 Nov 2021
- Primary completion10 Dec 2024
- Study completion8 Jan 2025
Why it stopped: The AZ-SWED trial was stopped by the National Heart, Lung, and Blood Institute (NHLBI) due to futility
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by University of ArizonaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This Phase III trial is designed as a parallel group, placebo-controlled, double-blind, randomized, multi-center evaluation of AZ for the treatment of acute wheezing episodes.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 840 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arizona
- Sponsor type
- University, hospital or other
- Collaborators
- University of Utah, Emory University, Morgan Stanley Children's Hospital, University of Pittsburgh, Children's Hospital and Health System Foundation, Wisconsin, Children's Hospital of Philadelphia, Children's Hospital Medical Center, Cincinnati, Boston Children's Hospital, University of Texas Southwestern Medical Center
- Responsible party
- Principal investigator, Fernando Martinez, University of Arizona
- Investigators
- Fernando D Martinez, MD, Principal investigator, University of ArizonaKurt Denninghoff, MD, Principal investigator, University of ArizonaCharlie Casper, PhD, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04669288
- Sponsor's protocol ID
- UG3HL147016
- Acronym
- AZ-SWED
- Status last verified
- Mar 2026
- First submitted
- 2 Dec 2020
- Last updated
- 23 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: After subject enrollment and follow up have been completed, the DCC may prepare a final study database for analysis. A releasable database will be produced and completely de-identified in accordance with the definition provided in the Health insurance Portability and Accountability Act (HIPAA). HIPAA will be recoded in a manner that will make it impossible to deduce or impute the specific identity of any patient. The database will not contain any institutional identifiers. This releasable database will be forwarded to the Biologic Specimen and Data Repository Information Coordinating Center (BIOLINCC) or, in case AZ-SWED samples and data are not deposited in BIOLINCC, to users in electronic form, in accordance with policies determined by the investigators and funding sponsors.
Publications
Denninghoff KR, Casper TC, Zorc JJ, Ruddy RM, Satola S, Wendt WJ, Morris CR, Tavarez MM, Lipshaw MJ, Kwok MY, Nesiama JO, Nelson KA, Webb M, Martinez FD; PECARN AZ-SWED Trial Study Group. Azithromycin for Preschoolers with Wheezing in the Emergency Department. N Engl J Med. 2026 May 18:10.1056/NEJMoa2516505. doi: 10.1056/NEJMoa2516505. Online ahead of print.
PubMed 42149992
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- AZithromycin Therapy in Preschoolers With a Severe Wheezing Episode Diagnosed at the Emergency Department (AZ-SWED)
- ClinicalTrials.gov ID
- NCT04669288
- Acronym / sponsor ID
- AZ-SWED / UG3HL147016
- Keywords
- Wheezing Lower Respiratory Illness (WLRI)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The AZ-SWED trial was stopped by the National Heart, Lung, and Blood Institute (NHLBI) due to futility
- Enrolment
- 840 participants (actual)
- Lead sponsor
- University of ArizonaUniversity, hospital or other
- Collaborators
- University of Utah, Emory University, Morgan Stanley Children's Hospital, University of Pittsburgh, Children's Hospital and Health System Foundation, Wisconsin, Children's Hospital of Philadelphia, Children's Hospital Medical Center, Cincinnati, Boston Children's Hospital, University of Texas Southwestern Medical Center
- Study start
- 22 Nov 2021 (actual)
- Primary completion
- 10 Dec 2024 (actual)
- Study completion
- 8 Jan 2025 (actual)
- First posted
- 16 Dec 2020 (actual)
- Results
- Posted 23 Jun 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
AZ-SWED is a parallel group, double blind, placebo control efficacy clinical trial with two separate hypotheses. The trial compared the 5-day outcome of preschool children presenting to an Emergency Department (ED) with an acute, severe wheezing episode and treated with either once daily oral Azithromycin (12 mg/kg/day for 5 days) or placebo. The AZ-SWED researchers made separate comparisons in children in whom specific pathogenic bacteria isolated from nasopharyngeal swabs, and in those in whom they were not isolated. The primary outcome was the Asthma Flare-up Diary for Young Children (ADYC), a validated instrument that caregivers will transmit electronically daily after discharge from the ED. Families were contacted daily during the five-day treatment to collect the ADYC, and to assess compliance and complications. A randomly chosen subset of enrolled children participated in two follow-up visits 5-8 days and 14-21 days after visit 1 to assess development of resistance to study drug and treatment response related changes in the airway microbiome.
Detailed description
This Phase III trial is designed as a parallel group, placebo-controlled, double-blind, randomized, multi-center evaluation of AZ for the treatment of acute wheezing episodes. The study recruited eligible patients from seven EDs. We tested two primary hypotheses: 1) AZ (12 mg/Kg/day) given for 5 days to preschool children with severe acute wheezing and harboring any of three specific pathogenic bacteria (H influenzae, M catarrhalis, or S pneumonia) in their nasopharynx will decrease the severity of the acute episode; and 2) AZ given on an identical schedule and dose will decrease the severity of wheezing episodes in children who do not harbor any of these three pathogenic bacteria in their nasopharynx.
This study had three visits. All enrolled patients participated on the Day 0 visit for screening, the informed consent process, enrollment, randomization, treatment initiation and dispensing drug. A sub-group of randomly selected patients participated in two follow-up visits on Day 5 - 8 and Day 14 - 21 where they were tested for antibiotic resistance.
The primary outcome was the sum of the Asthma Flare-up Diary for Young Children (ADYC) score, a validated instrument completed by the parent or guardian of the enrolled children during the 5-day treatment period. Secondary outcomes will include (1) ED length of stay (2) hospital length of stay, and (3) return ED visits or hospitalizations within 72 hours after randomization.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- This Phase III trial is designed as a parallel group, placebo-controlled, double-blind, randomized, multi-center evaluation of AZ for the treatment of acute wheezing episodes.
| Arm | Type | Receives |
|---|---|---|
| Treatment - Active | Active comparator | Drug: AzithromycinEligible participants were randomly assigned to the Azithromycin arm (1:1) |
| Treatment - Placebo | Placebo comparator | Drug: PlaceboEligible patients were randomly assigned to the placebo arm, per the randomization schedule (1:1). |
Who may qualify
- Ages
- 18 to 60 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Age 18 months to <60 months.
- The presence of expiratory wheezing as ascertained by a physician or nurse practitioner at admission to the ED.
- A Pediatric Respiratory Assessment Measurement (PRAM) score of greater than or equal to 4 at any time during the ED admission.
Key exclusion criteria (25 listed)
- Presence of acute infection that requires systemic antibiotics, as determined by the physician.
- Current or previous use of systemic antibiotics within the last 2 weeks.
- Current or previous use of a steroid for wheezing within the last 2 weeks.
- Suspected foreign body induced aspiration during the last 2 weeks.
- A known systemic illness (other than allergy) including but not limited to:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Azithromycinoral azithromycin (12 mg/kg per day for 5 days) Local investigational drug pharmacies were provided with active study medication (azithromycin) from a central pharmacy. Azithromycin was reconstituted with water at the local pharmacy, and resembled placebo with regards to appearance, flavor, consistency and packaging. | Drug | Treatment - Active |
| Placebooral placebo (12 mg/kg per day for 5 days) Local investigational drug pharmacies were provided with placebo from a central pharmacy. Placebo was reconstituted with water at the local pharmacy, and resembled azithromycin with regards to appearance, flavor, consistency and packaging. | Drug | Treatment - Placebo |
Primary outcome
ADYC (Median, IQR)
Time frame: 5 day course of azithromycin
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.
3 secondary outcomes
ED Length of Stay (Median, IQR)
Time frame: From admission at ED to discharge from ED, up to 23 hours and 59 minutes
Hospital Length of Stay (Median, IQR)
Time frame: From hospital admission to discharge from hospital
Return Visit
Time frame: Within 72 hours after randomization
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42149992Denninghoff KR, Casper TC, Zorc JJ, Ruddy RM, Satola S, Wendt WJ, Morris CR, Tavarez MM, Lipshaw MJ, Kwok MY, Nesiama JO, Nelson KA, Webb M, Martinez FD; PECARN AZ-SWED Trial Study Group. Azithromycin for Preschoolers with Wheezing in the Emergency Department. N Engl J Med. 2026 May 18:10.1056/NEJMoa2516505. doi: 10.1056/NEJMoa2516505. Online ahead of print.
- Individual participant dataSharing planned: No. After subject enrollment and follow up have been completed, the DCC may prepare a final study database for analysis. A releasable database will be produced and completely de-identified in accordance with the definition provided in the Health insurance Portability and Accountability Act (HIPAA). HIPAA will be recoded in a manner that will make it impossible to deduce or impute the specific identity of any patient. The database will not contain any institutional identifiers. This releasable database will be forwarded to the Biologic Specimen and Data Repository Information Coordinating Center (BIOLINCC) or, in case AZ-SWED samples and data are not deposited in BIOLINCC, to users in electronic form, in accordance with policies determined by the investigators and funding sponsors.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fernando D Martinez, MD principal investigator
University of Arizona
Kurt Denninghoff, MD principal investigator
University of Arizona
Charlie Casper, PhD principal investigator
University of Utah
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Azithromycin in people with Asthma and Wheezing, run by University of Arizona at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ADYC (Median, IQR) (time frame: 5 day course of azithromycin). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04669288, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2026.