AZithromycin Therapy in Preschoolers With a Severe Wheezing Episode Diagnosed at the Emergency Department

NCT04669288 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: UG3HL147016
• Study Type: interventional
• Target: 840
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Asthma; Wheezing

Keywords

Wheezing Lower Respiratory Illness (WLRI)

Outcome Measures

Primary Outcomes (1)

• Asthma Flare-up Diary for Young Children

  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 Outcomes (2)

• Length of Stay

  72 hours after randomization

• Number of participants that develop Azithromycin resistant organisms

  21 days after randomization

Study Arms (2)

Treatment - Active

ACTIVE COMPARATOR

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

Treatment - Placebo

PLACEBO COMPARATOR

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

Interventions

Azithromycin DRUG

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.

Treatment - Active

Placebo DRUG

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.

Treatment - Placebo

Eligibility Criteria

• Age: 18 Months - 60 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

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

Study Sites (8)

Children's Healthcare of Atlanta, Emory University

Atlanta, Georgia, 30322, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Children's Hospital of New York Medical Center

New York, New York, 10032, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

The Children's Hospital of Philadelphia (CHOP)

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

The Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Asthma; Respiratory Sounds

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Fernando D Martinez, MD

  University of Arizona

  PRINCIPAL INVESTIGATOR

• Kurt Denninghoff, MD

  University of Arizona

  PRINCIPAL INVESTIGATOR

• Charlie Casper, PhD

  University of Utah

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Equal allocation randomization tables will be provided by the Data Coordinating Center (DCC) to the central research pharmacy. The central research pharmacy will prepare consecutively numbered study kits according to the randomization schedule. Study kits will be sent to the clinical sites. Study products will be labeled with numerical codes that will maintain allocation concealment. Blinding/labeling of study medication bottles will be completed at the site pharmacy prior to dispensing to the patient. Randomization tables will be created at the Data Coordinating Center using permuted-block randomization stratified by clinical site and baseline severity of symptoms. Permuted blocks of random lengths 2, 4, and 6 will be used. The randomization number will be recorded in the database.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Regents' Professor

Model Details: 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. 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 and dispensing. 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.

Study Record Dates

• First Submitted: December 2, 2020
• First Posted: December 16, 2020
• Study Start: September 22, 2021
• Primary Completion: December 10, 2024
• Study Completion: January 8, 2025
• Last Updated: March 4, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)