Characterization of Bronchodilator Response in Children With Bronchiolitis Using Phenotypic and Genotypic Features

NCT ID: NCT06946264

Last Updated: 2025-04-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-08
• Study Completion Date: 2030-12-31

Brief Summary

Bronchiolitis is the leading cause of pediatric morbidity and healthcare costs. Despite the commonplace use of bronchodilator treatments, like albuterol, in conditions like asthma, their efficacy in bronchiolitis remains controversial due to the heterogeneity in patient response. Although studies indicate that bronchodilators do not enhance outcomes in bronchiolitis, meta-analyses can obscure the heterogeneity of treatment effects. While bronchodilator response genetics have not been explored in bronchiolitis, treatment effectiveness variations often depend on genomic factors. Genome-wide association studies (GWAS) have linked genetic variants with bronchodilator response and outcomes in childhood asthma, suggesting a bronchodilator-responsive genotype. This proposal aims to extend this paradigm to bronchiolitis, addressing the gap in knowledge where GWAS and clinical characteristics intersect. The proposed study's objective is to characterize phenotypic and genotypic variations of children with bronchiolitis and their association with bronchodilator response. We hypothesize that children with bronchiolitis who exhibit clinical and historical characteristics associated with atopy and specific physical findings have genetic variants linked to bronchodilator response. To achieve this, we propose to (Aim 1) define airway responsiveness to bronchodilator treatment in children with bronchiolitis using the change in respiratory score, (Aim 2a) identify the associations between candidate genetic variants and bronchodilator response among children with bronchiolitis, and (Aim 2b) determine the associations between candidate genetic variants and clinical patient data to identify bronchodilator-responsive children with bronchiolitis. A prospective, double-blind, randomized, placebo-controlled trial of a single albuterol dose in children aged 3 to 24 months presenting with bronchiolitis to the emergency department will be conducted to achieve these aims. Patient information and respiratory assessment outcomes will be collected before and after intervention. Blood, urine, DNA buccal swabs, and nasopharyngeal swabs will also be collected. Completion of these aims will result in a novel clinical prediction model for bronchodilator response determination in bronchiolitis, integrating clinical, physical, and genetic data. Furthermore, this research supports the candidates' career development goals of advancing training in clinical trial research design and execution and becoming an expert in clinical and translational methods to enhance pediatric emergency department health and outcomes. Ultimately, this work will inform an R01 application to validate an evidence-based prediction rule for identifying bronchodilator-responsive children with bronchiolitis through a multi-center emergency medicine research network, optimizing therapeutic approaches, and reducing resource use in those with a low likelihood of bronchodilator response.

Conditions

Bronchiolitis; Bronchodilator Agents

Study Design

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

Study Groups

Bronchodilator arm

Children with bronchiolitis will be randomized to an intervention arm to be administered as a nebulization (albuterol sulfate 2.5mg/ 3mL inhalation solution). The intervention drug will be placed in a sealed manila envelope, randomized in advance by a Nemours Investigational Drug Pharmacist, and stored in the ED pyxis.

Group Type: EXPERIMENTAL

Albuterol Sulfate, 2.5 Mg/3 mL (0.083%) Inhalation Solution

Intervention Type: DRUG

Children with bronchiolitis will be randomized to an intervention arm to be administered as a nebulization (albuterol sulfate 2.5mg/ 3mL inhalation solution). The intervention drug will be placed in a sealed manila envelope, randomized in advance by a Nemours Investigational Drug Pharmacist, and stored in the ED pyxis.

Normal saline arm

Children with bronchiolitis will be randomized to an intervention arm to be administered as a nebulization (sodium chloride 0.9%/ 3mL inhalation solution). The intervention drug will be placed in a sealed manila envelope, randomized in advance by a Nemours Investigational Drug Pharmacist, and stored in the ED pyxis.

Group Type: PLACEBO_COMPARATOR

Sodium Chloride 0.9% Inhl 3Ml

Intervention Type: DRUG

Children with bronchiolitis will be randomized to an intervention arm to be administered as a nebulization (sodium chloride 0.9% 3mL inhalation solution). The intervention drug will be placed in a sealed manila envelope, randomized in advance by a Nemours Investigational Drug Pharmacist, and stored in the ED pyxis.

Interventions

Albuterol Sulfate, 2.5 Mg/3 mL (0.083%) Inhalation Solution

Children with bronchiolitis will be randomized to an intervention arm to be administered as a nebulization (albuterol sulfate 2.5mg/ 3mL inhalation solution). The intervention drug will be placed in a sealed manila envelope, randomized in advance by a Nemours Investigational Drug Pharmacist, and stored in the ED pyxis.

Intervention Type: DRUG

Sodium Chloride 0.9% Inhl 3Ml

Children with bronchiolitis will be randomized to an intervention arm to be administered as a nebulization (sodium chloride 0.9% 3mL inhalation solution). The intervention drug will be placed in a sealed manila envelope, randomized in advance by a Nemours Investigational Drug Pharmacist, and stored in the ED pyxis.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Children between 3 to 24 months of age
• Clinical diagnosis of bronchiolitis by the treating provider(s), defined by the American Academy of Pediatrics as a clinical syndrome involving lower respiratory tract symptoms
• Children who either have no history of prematurity or have a history of prematurity but without associated co-morbidities
• Emergency department (ED) visit to seek care at Nemours Children's Health-Florida (NCH-FL)

Exclusion Criteria

• Patients previously enrolled in the PI's K12 study
• Documented history of asthma or reactive airway disease
• Co-morbidities affecting airway response (e.g., chronic lung disease, bronchopulmonary dysplasia, bronchiectasis, congenital heart disease, immunodeficiency, neurologic condition)
• Diagnosis of pneumonia by chest radiography
• Inhaled, nebulized, or oral corticosteroid use within 72 hours of ED evaluation
• Inhaled, nebulized, or oral bronchodilator administration within 4 hours of ED arrival

• Minimum Eligible Age: 3 Months
• Maximum Eligible Age: 24 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nemours Children's Clinic

OTHER

Sponsor Role: lead

Responsible Party

Andrea Rivera-Sepulveda

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Nemours Children's Health

Orlando, Florida, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Andrea Rivera-Sepulveda, MD, MSc

Role: CONTACT

andrea.rivera-sepulveda@nemours.org

407-489-6847

References

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Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1866573

Identifier Type: -

Identifier Source: org_study_id