AZithromycin Therapy in Preschoolers With a Severe Wheezing Episode Diagnosed at the Emergency Department (AZ-SWED)

February 27, 2025 updated by: Fernando Martinez, University of Arizona

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 will compare 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 will make separate comparisons in children in whom specific pathogenic bacteria are isolated from nasopharyngeal swabs, and in those in whom they are not isolated. The primary outcome will be the Asthma Flare-up Diary for Young Children (ADYC), a validated instrument that caregivers will transmit electronically daily after discharge from the ED. Families will be contacted daily during the five-day treatment to collect the ADYC, and to assess compliance and complications. A randomly chosen subset of enrolled children will participate 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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 will recruit eligible patients from an estimated six EDs and enroll up to 2,000 patients. We will test 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. We will also explore whether variants in the genes encoding for Cadherin Related Family Member 3 (CDHR3), Interleukin-8 (IL-8) and in the 17q asthma-related gene cluster predict response to AZ.

This short-term study has three planned visits. All enrolled patients will participate on the Day 0 visit for screening, the informed consent process, enrollment, randomization, treatment initiation and dispensing drug. A sub-group of 370 randomly selected patients will participate in two follow-up visits on Day 5 - 8 and Day 14 - 21 where they will be tested for antibiotic resistance. The primary outcome will be 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 Type

Interventional

Enrollment (Actual)

840

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Children's Healthcare of Atlanta, Emory University
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital
    • New York
      • New York, New York, United States, 10032
        • Children's Hospital of New York Medical Center
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • The Children's Hospital of Philadelphia (CHOP)
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh Medical Center
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • The Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 5 years (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
    • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Treatment - Active
Eligible patients will be randomly assigned to one of two treatment groups (1:1) and one arm will be administered the active drug per the randomization schedule. Study medication will be provided to parents/guardians, along with instructions, for home-based administration. The first dose of the study medication will be administered before discharge from the ED.
Drug: Azithromycin

oral azithromycin (12 mg/kg per day for 5 days)

Local investigational drug pharmacies will be provided with active study medication (azithromycin) from a central pharmacy. Azithromycin will be reconstituted with water at the local pharmacy, and will resemble placebo with regards to appearance, flavor, consistency and packaging.
Placebo Comparator: Treatment - Placebo
Eligible patients will be randomly assigned to one of two treatment groups (1:1) and one arm will be administered placebo per the randomization schedule. Study medication will be provided to parents/guardians, along with instructions, for home-based administration. The first dose of the study medication will be administered before discharge from the ED.
Drug: Placebo

oral placebo (12 mg/kg per day for 5 days)

Local investigational drug pharmacies will be provided with placebo from a central pharmacy. Placebo will be reconstituted with water at the local pharmacy, and will resemble azithromycin with regards to appearance, flavor, consistency and packaging.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Asthma Flare-up Diary for Young Children
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) will fill 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 will be 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.
5 day course of azithromycin

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Length of Stay
Time Frame: 72 hours after randomization
Secondary outcomes will include (1) ED length of stay (2) hospital length of stay, and (3) return ED visits or hospitalizations.
72 hours after randomization
Number of participants that develop Azithromycin resistant organisms
Time Frame: 21 days after randomization
Presence of azithromycin-resistant organisms will be assessed at baseline, and again at two follow-up visits 5-8 days and 14-21 days after enrollment in a randomly selected subset of trial subjects. A total of 370 subjects will be selected for this follow-up. Subjects in whom resistance is detected at baseline will not be included in the analysis of development of bacterial resistance at follow-up. Among subjects that are negative for bacterial resistance at baseline, follow-up resistance will be tabulated by treatment. The absolute risk difference, together with a 95% one-sided confidence interval, will be used to summarize treatment difference. Participants who harbor or do not harbor the three pathogenic bacteria will be included in these analyses.
21 days after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Arizona

Collaborators

Children's Hospital of Philadelphia
University of Pittsburgh
Boston Children's Hospital
Emory University
Children's Hospital Medical Center, Cincinnati
University of Utah
Children's Hospital and Health System Foundation, Wisconsin
Morgan Stanley Children's Hospital

Investigators

  • Principal Investigator: Kurt Denninghoff, MD, University of Arizona
  • Principal Investigator: Charlie Casper, PhD, University of Utah
  • Principal Investigator: Fernando D Martinez, MD, University of Arizona

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 22, 2021

Primary Completion (Actual)

December 10, 2024

Study Completion (Actual)

January 8, 2025

Study Registration Dates

First Submitted

December 2, 2020

First Submitted That Met QC Criteria

December 11, 2020

First Posted (Actual)

December 16, 2020

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 27, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UG3HL147016 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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