Bilevel Positive Airway Pressure (BPAP) for Severe Asthma

Official title

Bilevel Positive Airway Pressure (BPAP) for Severe Asthma Exacerbations: A Randomized Controlled Trial

Overview

The goal of this clinical trial is to assess the feasibility of early initiation of bilevel positive airway pressure (BPAP) in the emergency department (ED) for children with severe asthma exacerbations. It will also collect preliminary data on the safety and potential effectiveness of this approach. The main questions it aims to answer are: 1. Can eligible patients be successfully enrolled and complete study procedures across multiple sites? 2. What safety events occur with early BPAP use in this population? 3. How do clinical outcomes (such as symptom improvement and need for intensive care) compare between early BPAP and standard care? Researchers will compare early initiation of BPAP plus standard asthma therapy to standard asthma therapy alone to determine whether early BPAP is a feasible and potentially beneficial treatment strategy. Participants will 1) receive standard asthma therapy with or without early BPAP in the ED, 2) be monitored closely during the ED visit and hospitalization, and 3) have clinical data collected from routine care, including asthma severity scores, treatments, and outcomes. The study will enroll approximately 36 participants (about 12 per site) across three sites over one year to inform a future multicenter randomized controlled trial.

Detailed description

Severe asthma exacerbations are a common reason for pediatric emergency department (ED) visits, hospital admissions, and pediatric intensive care unit (PICU) use. Although first-line therapies such as inhaled beta-agonists, anticholinergics, and systemic corticosteroids are well established, the optimal second-line treatment for children who remain in moderate to severe respiratory distress is unclear.

Bilevel positive airway pressure (BPAP) is a form of non-invasive positive pressure ventilation that may improve airway patency, reduce work of breathing, improve ventilation-perfusion matching, and enhance delivery of inhaled bronchodilator therapy. Prior pediatric studies suggest potential physiologic and clinical benefit, but available randomized trials have been small and have generally evaluated BPAP after PICU admission rather than early in the ED course. Therefore, the feasibility, safety, and potential clinical impact of early ED initiation of BPAP remain uncertain.

This multicenter, randomized, unblinded feasibility trial will enroll approximately 36 children across three sites. Participants will be children with severe asthma exacerbations who remain symptomatic after completion of standard first-line therapy and continue to require continuous albuterol. Patients will be randomized to receive either BPAP plus continuous albuterol or continuous albuterol alone during an approximately 2-hour intervention period. BPAP will be delivered using FDA-cleared devices, with mask interface and pressure settings managed according to routine clinical practice. After the intervention period, all further asthma treatment and respiratory support will be determined by the treating clinical team.

The primary purpose of this study is to assess feasibility of conducting a future definitive multicenter randomized trial. Feasibility domains include patient identification, consent and assent processes, timely randomization, BPAP initiation and adherence, completion of asthma severity assessments, and collection of clinical and safety data. Clinical outcomes, including asthma severity, duration of continuous albuterol, BPAP use, ED disposition, PICU and hospital admission, length of stay, and readmission, will be summarized descriptively. Safety monitoring will include adverse events potentially related to BPAP or continuous albuterol, including air leak syndrome, vomiting, aspiration, hypotension, skin breakdown, tachycardia, and tremor.

This feasibility trial is not powered to detect treatment efficacy. Results will be used to refine trial procedures, assess protocol adherence, estimate enrollment and data completion rates, and inform the design of a future multicenter randomized trial evaluating whether early ED initiation of BPAP reduces critical care resource use and improves outcomes in children with severe asthma exacerbations.

Interventions

• Device Bilevel positive airway pressure ventilation
  This study involves non-invasive positive pressure ventilation (NIPPV) delivered as bilevel positive airway pressure (BPAP) in children aged 5-17 years presenting to the pediatric emergency department with severe asthma exacerbations. BPAP will be administered using FDA-cleared devices according to their intended use and standard clinical practice. Therapy will be delivered via an appropriately fitted nasal or face mask and managed by trained clinical staff. Ventilator settings will be adjusted

Primary outcome measures

• Number of eligible patients who consent [Time frame: From screening through randomization, up to 2 hours]
• Proportion of participants who adhere to the BPAP protocol among all those assigned to the BPAP arm [Time frame: From randomization through end of 2-hour intervention]

Secondary outcome measures (12)

• Potential efficacy outcome: Change in Pediatric Respiratory Assessment Measure (PRAM) score [Time frame: Pre-intervention to end of intervention, approximately 3 hours total]
• Potential efficacy outcome: Duration of continuous albuterol use [Time frame: From randomization through hospital discharge beyond the intervention period, up to 120 hours.]
• Potential efficacy outcome: Duration of BPAP use [Time frame: From randomization through hospital discharge beyond the intervention period, up to 120 hours]
• Potential efficacy outcome: PICU admission [Time frame: Disposition determined 2 hours after completion of the intervention period]
• Potential efficacy outcome: Hospital admission [Time frame: Disposition determined 2 hours after completion of the intervention period]
• Potential efficacy outcome: PICU length of stay [Time frame: From PICU admission to PICU discharge, up to 120 hours]
• Potential efficacy outcome: Hospital length of stay [Time frame: From hospital admission to hospital discharge, up to 120 hours]
• Safety outcome: Air Leak Syndrome [Time frame: From randomization until 4 hours post-randomization or until ED discharge, whichever occurs first.]
• Safety outcome: Vomiting [Time frame: From randomization until 4 hours post-randomization or until ED discharge, whichever occurs first.]
• Safety outcome: Pulmonary aspiration [Time frame: From randomization until 4 hours post-randomization or until ED discharge, whichever occurs first.]
• Safety outcome: Systolic hypotension [Time frame: From randomization until 4 hours post-randomization or until ED discharge, whichever occurs first.]
• Safety outcome: Facial skin breakdown [Time frame: From randomization until 4 hours post-randomization or until ED discharge, whichever occurs first.]

Eligibility criteria

Inclusion criteria

• 5 to 17 years of age (inclusive) presenting to the ED with an asthma exacerbation.
• Demonstrate moderate-severe asthma exacerbation at triage (i.e., receive an institutional asthma score equivalent to moderate-severe asthma exacerbation or a Pediatric Respiratory Assessment Measure (PRAM) score of 6 or above).

Exclusion criteria

• Prior participation in the study.
• Use of BPAP at any time within approximately 12 hours for this acute asthma exacerbation, including in prehospital, ED, or inpatient settings, prior to randomization.
• Receipt of continuous albuterol for over 150 minutes prior to being approached for consent.
• If a blood gas is obtained, PaCO2 greater than 60 mmHg on the most recent blood gas prior to being approached for consent.

Note: Blood gas values are not required for eligibility confirmation.

• Anticipated immediate need (i.e., within approximately an hour after completion of first-line therapy) for invasive mechanical ventilation (e.g., endotracheal tube or laryngeal mask airway) or non-invasive mechanical ventilation (e.g., continuous positive airway pressure (CPAP) or BPAP), as determined by the treating physician.
• Presence of a tracheostomy or a baseline requirement for noninvasive ventilation.
• Wheezing due to non-asthma causes (e.g., foreign body, tracheomalacia, vocal cord dysfunction, pulmonary edema, uncorrected congenital heart disease, cystic fibrosis, or anaphylaxis).
• Absolute or relative contraindication to BPAP, defined as any of the following:

• Facial trauma within the area where the face mask would be applied for BPAP (excluding minor abrasion or cuts on forehead or skull).
• Uncontrollable vomiting (i.e., > 3 episodes within approximately 1 hour prior to being approached for consent).
• Hypotension for age, defined as systolic blood pressure (SBP) less than 70 plus twice the patient's age in years (i.e., SBP < 70 + \[2 x age in years\]).
• Glasgow Coma Score of 8 or less.
• Known or clinical suspicion for air leak syndrome (e.g., pneumothorax, pneumomediastinum, pneumopericardium, or subcutaneous emphysema).
• Weight < 20 kg.
• Presence of an intra-abdominal mass compressing the stomach (e.g., due to tumor or large volume ascites) through EMR or medical history.
• Known or suspected pregnancy by history or if pregnancy test completed by clinical team.
• Any medical condition that, in the opinion of a site investigator, could 1) lead to difficulty complying with protocol procedures, 2) interfere with the safe completion of the study, or 3) affect the validity of the endpoint assessments.
• PRAM score less than 7 or greater than 10 based on concurrent clinical assessment by a healthcare provider after completion of standard first-line therapies, which is defined as receiving all of the following prior to ED arrival or during the ED encounter for this acute asthma exacerbation:

• Albuterol with or without ipratropium bromide, either at least 3 albuterol doses via inhalation method (e.g., metered-dose inhaler (MDI) or nebulized) or at least one hour of continuous albuterol (i.e., continuous nebulized albuterol or three consecutive intermittent nebulized albuterol treatments as bridging therapy).
• Corticosteroids (e.g., Prednisolone, Prednisone, Dexamethasone/Decadron, or Methylprednisolone) via enteral, intravenous, or intramuscular methods.

Note: Oxygen is not a required first-line therapy.

• Do not require continuous albuterol or a second round of albuterol treatments (e.g., three back-to-back treatments or one hour of burst albuterol treatment) following completion of standard first-line therapies.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 3 centers

• Columbia University Irving Medical Center — New York
• Nationwide Children's Hospital — Columbus
• Children's Hospital of Philadelphia — Philadelphia

Identifiers

NCT: NCT07582211 · ACYY1620 · 1R34HL173384-01A1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗