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
Recruitment Status
Recruiting
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.
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.
Intervention
Intervention Type
Intervention Name
Drug
Azithromycin
Drug
Placebo
Phase
Phase 3
Gender
All
Min Age
18 Months
Max Age
60 Months
Download Date
January 3, 2024
Principal Investigator
Fernando Martinez
Primary Contact Information
For more information on this trial, visit clinicaltrials.gov.
Contact
For more information and to contact the study team: