Aerosolized Albuterol Use in Severe BPD

Safety and Efficacy of Aerosolized Albuterol in Mechanically Ventilated Infants With Bronchopulmonary Dysplasia (BDP)

Currently several dose schedules of Albuterol are administered via nebulization to infants in the neonatal and infant intensive care unit (N/IICU). As Albuterol is not FDA approved for this population (under 2 years) there is no standard recommended dose. Aerosolized Albuterol is one of the most widely used therapies that are utilized for infants with chronic lung disease. The common practice in the N/IICU is weight base dosing of all medications. This contradicts the aerosol science recommendations, which advise not to titrate doses by weight as the patient naturally self-regulates their dose according to the change in minute ventilation with age. In addition, the wide use of aerosolized Albuterol in the infant with Bronchopulmonary Dysplasia (BPD) has little current evidence of efficacy in this disease. Understanding the appropriate dose for effective treatment as well as the indication for use in the BPD population would provide the clinician with useful guidelines.

The investigators propose to analyze the safety and efficacy of aerosolized albuterol in infants with BPD comparing the recommended dose per aerosolization literature with the common dosing practices at The Children's Hospital of Philadelphia (CHOP) as well as placebo.

Study Overview

• Status: Completed
• Conditions: Severe Bronchopulmonary Dysplasia
• Intervention / Treatment: Drug: Albuterol Sulfate; Drug: Sterile Saline

Detailed Description

This is a randomized, blinded cross-over study of infants with a diagnosis of Severe BPD that are mechanically ventilated. Participants will receive 3 sets of treatment (2.5mg Albuterol, 1.25mg Albuterol, 3ml normal saline placebo), in random order. Each treatment will be administered every 4 hours for 24 hours. After a 6 hour washout phase, the next group of interventions will be applied. Following another wash-out phase, the final group of intervention will be applied. Pulmonary mechanics from the ventilator (e.g. airway compliance, airway resistance, tidal volume, peak inspiratory pressure, Forced Expiratory Flow at 75% of forced vital capacity, etc.) and the patient short term response to therapy (heart rate, blood pressure, heart rhythm) will be assessed for the duration of the treatment period.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Infants greater than or equal to 36 weeks corrected gestational age to one year of age
2. Diagnosis of BPD in accordance with The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) definition
3. May have a current order for short acting bronchodilator, not required
4. May have congenital anomalies unless one or more of the exclusion criteria are met, not required
5. Receiving conventional mechanical ventilation via an artificial airway (endotracheal tube or tracheostomy) via Draeger V500 Ventilator
6. Parental/guardian permission (informed consent)

Exclusion Criteria:

1. Airway leak greater than 10%
2. Unilateral lung disease
3. Current order for inhaled anticholinergic (i.e. ipratropium bromide)
4. Active pulmonary or systemic infection
5. Scheduled order for other medication that cause bronchodilation (i.e. atrovent, magnesium sulfate, ketamine, etc.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Full Dose Albuterol Sulfate; 2.5mg of Albuterol Sulfate will be administered via nebulizer and mechanical ventilator	Drug: Albuterol Sulfate; Subjects will receive a dose of study medication every 4 hours for 24 total hours; Other Names: Salbutamol
Active Comparator: Half Dose Albuterol Sulfate; 1.25mg of Albuterol Sulfate will be administered via nebulizer and mechanical ventilator	Drug: Albuterol Sulfate; Subjects will receive a dose of study medication every 4 hours for 24 total hours; Other Names: Salbutamol
Placebo Comparator: Sterile Saline; 3ml of 0.9% sterile saline will be administered via nebulizer and mechanical ventilator	Drug: Sterile Saline; Subjects will receive a dose of study medication every 4 hours for 24 total hours; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Expiratory Flow Between Pre and Post-medication Dosing	Expiratory flow at 75% of vital capacity (EF75) will be measured before beginning each treatment and again 15-30 min after each treatment phase. Therefore there will be 6 pairs (12) of EF values to determine the change in EF for each treatment. this measure is done by measuring the expiratory flow at 75% of exhalation on as measure on the flow volume loop of the ventilator. a single mechanical breath is chosen and the flow volume loop is frozen on the ventilator screen. the clinician can then scroll to measure total tidal volume for the breath, then multiple this volume by 0.25 (to ascertain the volume that the time point of 75% of exhalation), then scroll along the expiratory side of the flow volume loop until the calculated volume is reached and then the flow at that time point is recorded.	every 4 hours in each treatment group, up to 24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Heart Rate (Beats/Min) Between Pre and Post-medication Dosing	Heart rate will be measured before beginning each treatment and again 15-30 min after the conclusion of each treatment phase (4 hours). Therefore there will be 6 pairs of heart rates (12 measures), to determine the change in HR for each treatment group.	every 4 hours in each treatment group, up to 24 hours

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Investigators: Principal Investigator: Kevin Dysart, MD, Children's Hospital of Philadelphia

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: May 9, 2016
• First Submitted That Met QC Criteria: May 9, 2016
• First Posted (Estimate): May 10, 2016

Study Record Updates

• Last Update Posted (Actual): August 28, 2019
• Last Update Submitted That Met QC Criteria: August 15, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Ventilator-Induced Lung Injury; Bronchopulmonary Dysplasia; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Albuterol
• Other Study ID Numbers: 15-012264

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No