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

NCT ID: NCT04669288

Last Updated: 2025-03-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 840 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-22
• Study Completion Date: 2025-01-08

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.

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.

Conditions

Asthma; Wheezing

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Azithromycin

Intervention Type: 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 - 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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Months
• Maximum Eligible Age: 60 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Utah

OTHER

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: collaborator

Morgan Stanley Children's Hospital

OTHER

Sponsor Role: collaborator

University of Pittsburgh

OTHER

Sponsor Role: collaborator

Children's Hospital and Health System Foundation, Wisconsin

OTHER

Sponsor Role: collaborator

Children's Hospital of Philadelphia

OTHER

Sponsor Role: collaborator

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role: collaborator

Boston Children's Hospital

OTHER

Sponsor Role: collaborator

University of Arizona

OTHER

Sponsor Role: lead

Responsible Party

Fernando Martinez

Regents' Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Fernando D Martinez, MD

Role: PRINCIPAL_INVESTIGATOR

University of Arizona

Kurt Denninghoff, MD

Role: PRINCIPAL_INVESTIGATOR

University of Arizona

Charlie Casper, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Locations

Children's Healthcare of Atlanta, Emory University

Atlanta, Georgia, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Children's Hospital of New York Medical Center

New York, New York, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

The Children's Hospital of Philadelphia (CHOP)

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

The Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

Other Identifiers

UG3HL147016

Identifier Type: NIH

Identifier Source: org_study_id

View Link