Albuterol for Bronchiolitis

Overseen By Andrea Rivera-Sepulveda, MD, MSc

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Nemours Children's Clinic

Must not be taking: Corticosteroids, Bronchodilators

Disqualifiers: Asthma, Chronic lung disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: Immediate

400 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that participants do not use inhaled, nebulized, or oral corticosteroids within 72 hours before the emergency department visit and no bronchodilator use within 4 hours of arrival. If you are taking these medications, you may need to stop them before participating.

What data supports the effectiveness of the drug Albuterol for bronchiolitis?

A study found that nebulized albuterol significantly improved breathing and oxygen levels in infants with bronchiolitis compared to a placebo, indicating it can be an effective treatment for this condition. ^{1 2 3 4 5}

Is Albuterol generally safe for human use?

The provided research articles do not contain specific safety data for Albuterol or its use in treating bronchiolitis. However, Albuterol is a commonly used medication for asthma and other respiratory conditions, and it is generally considered safe when used as directed. ^{6 7 8 9 10}

How does the drug albuterol differ from other treatments for bronchiolitis?

Albuterol is unique for bronchiolitis as it is a bronchodilator (a drug that helps open the airways) typically used for asthma, but its use in bronchiolitis is debated due to mixed evidence of effectiveness. Unlike standard treatments, which often focus on supportive care, albuterol may be considered for specific cases, such as older infants with certain viral infections or those with a family history of asthma. ^{4 5 11 12 13}

Eligibility Criteria

This trial is for children aged 3 to 24 months who are presenting with bronchiolitis in the emergency department. The study aims to understand how these young patients respond to a common asthma medication, albuterol, based on their clinical symptoms and genetic makeup.

Inclusion Criteria

Emergency department (ED) visit to seek care at Nemours Children's Health-Florida (NCH-FL)

My child is between 3 to 24 months old.

I have been diagnosed with bronchiolitis.

Exclusion Criteria

I took asthma medication by mouth or inhaler within 4 hours before coming to the ER.

Patients previously enrolled in the PI's K12 study

My pneumonia was confirmed by a chest X-ray.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of albuterol or placebo via nebulization, with patient information and respiratory assessment outcomes collected before and after intervention

Immediate

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with genetic and clinical data collected to identify bronchodilator-responsive children

through study completion, an average of 1 year

Treatment Details

Interventions

• Albuterol

Trial Overview The trial tests whether a single dose of albuterol can improve breathing in infants with bronchiolitis compared to a placebo (saltwater solution). It's double-blind and randomized, meaning neither doctors nor participants know who gets the real medicine. Researchers will also look at genes that might predict who benefits from albuterol.

Participant Groups

Group I: Bronchodilator arm Experimental Treatment 1 Intervention

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 II: Normal saline arm Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Nemours Children's Clinic

Lead Sponsor

Trials

128

Recruited

18,000+

Findings from Research

A meta-analysis of 19 studies found that serious adverse events (SAEs) related to ALK inhibitors occurred in over 20% of patients, with ceritinib and brigatinib showing SAEs in more than 40% of participants, highlighting significant safety concerns.

Among the ALK inhibitors analyzed, alectinib was identified as the safest option, suggesting it may be preferable for patients due to its lower incidence of SAEs, particularly lung toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and serious adverse events of approved ALK inhibitors in malignancies: a meta-analysis. Hou, H., Sun, D., Liu, K., et al.[2020]

Interstitial lung disease (ILD) can be a serious side effect of oncological drugs, characterized by chronic lung inflammation and potential pulmonary fibrosis, highlighting the need for awareness among healthcare providers.

Prompt diagnosis and differentiation of drug-related pneumonia from other types of pneumonia are crucial for timely treatment adjustments, including stopping the offending drug and possibly starting immunosuppressive therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug-Related Pneumonitis in Cancer Treatment during the COVID-19 Era. Cherri, S., Noventa, S., Fanelli, M., et al.[2021]

A study of 130 treatment courses in 111 patients revealed that safety monitoring activities (SMAs) for EGFR and ALK inhibitors were inconsistently conducted, with prevalence ranging from 10.0% to 84.6%, and 31.5% of courses had no SMAs performed.

EGFR inhibitors were associated with a higher likelihood of SMAs being conducted compared to ALK inhibitors, highlighting the need for clinicians to closely follow FDA guidelines to ensure patient safety and monitor for serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Monitoring Activity During EGFR or Anaplastic Lymphoma Kinase Inhibitor Therapy for Patients With Lung Cancer. Singh, AM., Rubiera-Pebe, R., Ahmad, Y., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Albuterol in acute bronchiolitis--continued therapy despite poor response? [2013]

2. United States pubmed.ncbi.nlm.nih.gov

The use of albuterol in hospitalized infants with bronchiolitis. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Efficacy of albuterol in the management of bronchiolitis. [2013]

4. United States pubmed.ncbi.nlm.nih.gov

Nebulized albuterol in acute bronchiolitis. [2019]

5. Singapore pubmed.ncbi.nlm.nih.gov

For which infants with viral bronchiolitis could it be deemed appropriate to use albuterol, at least on a therapeutic trial basis? [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

The safety and serious adverse events of approved ALK inhibitors in malignancies: a meta-analysis. [2020]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Drug-Related Pneumonitis in Cancer Treatment during the COVID-19 Era. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Association between baseline pulmonary status and interstitial lung disease in patients with non-small-cell lung cancer treated with erlotinib--a cohort study. [2016]

9. United States pubmed.ncbi.nlm.nih.gov

Safety Monitoring Activity During EGFR or Anaplastic Lymphoma Kinase Inhibitor Therapy for Patients With Lung Cancer. [2023]

10. Japan pubmed.ncbi.nlm.nih.gov

[Analysis of risk factors of drug-induced lung injury in patients receiving gemcitabine treatment]. [2022]

11. Singapore pubmed.ncbi.nlm.nih.gov

Predictors for the prescription of albuterol in infants hospitalized for viral bronchiolitis. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Multicenter Study of Albuterol Use Among Infants Hospitalized with Bronchiolitis. [2023]

13. United States pubmed.ncbi.nlm.nih.gov

Randomized, double-blind, placebo-controlled trial of oral albuterol in infants with mild-to-moderate acute viral bronchiolitis. [2013]