Bilevel Positive Airway Pressure (BiPAP) for the Treatment of Moderate to Severe Acute Asthma Exacerbations

Overview

Bilevel Positive Airway Pressure (BiPAP) is increasingly being reported as an effective and safe method of respiratory support for children with severe asthma exacerbations unresponsive to standard therapies and with impending respiratory failure. Much of the evidence base supporting its use comes from retrospective observational studies, and there is currently a lack of data from randomized controlled trials to inform this practice. The investigators hypothesize that the use of BiPAP in children with moderate to severe asthma exacerbations could reduce the length of hospital stay, need for invasive ventilation, and use of intravenous bronchodilators. The investigators aim to test this hypothesis by randomizing children attending the Emergency Department with a moderate to severe clinical severity score refractory to inhaled bronchodilators to receive either BiPAP in addition to standard asthma care, or standard care alone.

Full Title of Study: “A Prospective Open Randomized Clinical Trial Comparing Bilevel Positive Airway Pressure (BiPAP) Therapy Against Standard Therapy for Children Hospitalized With an Acute Exacerbation of Asthma Unresponsive to Inhaled Bronchodilators.”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 2015

Detailed Description

Children aged 2 – 18 years presenting to the Emergency Department (ED) with a moderate or severe asthma exacerbation (Pediatric Respiratory Assessment Measure (PRAM) of > 3) who fail to improve clinically with standard ED management with inhaled salbutamol and ipratropium will be randomized to receive either standard asthma management according to our local severe asthma guideline or management with BiPAP in addition to standard care. Both groups will receive a comparable dose of systemic steroid and hourly salbutamol inhalers with subsequent weaning according to PRAM score. Patients randomized to receive BiPAP will be admitted to the Pediatric Intensive Care Unit (PICU) and those randomized to the control group will be admitted to the medical ward. Both groups will be monitored with 3-hourly PRAM scoring through the duration of their admission.

Interventions

  • Device: Bilevel Positive Airway Pressure (BiPAP) (Trilogy BiPAP, Philips Respironics)
    • Children in the intervention group will receive BiPAP (Trilogy, Philips Respironics; spontaneous trigger mode) via a nasal or full face mask. End expiratory positive airway pressure (EPAP) will be set at 5cm H20. Inspiratory positive airway pressure (IPAP) will be titrated to achieve a tidal volume of 6 – 9 ml/kg. These settings will remain unchanged throughout the study period.
  • Other: Standard care
    • Standard care according to the hospital severe asthma protocol

Arms, Groups and Cohorts

  • Experimental: BiPAP plus standard care
    • Bilevel Positive Airway Pressure (BiPAP) plus standard care according to the hospital’s severe asthma protocol
  • Active Comparator: Standard care alone
    • Standard care according to the hospital’s severe asthma protocol

Clinical Trial Outcome Measures

Primary Measures

  • Pediatric Respiratory Assessment Measure (PRAM) clinical severity score of ≤ 3 (mild)
    • Time Frame: Assessed at initiation, and 3-hourly thereafter until hospital discharge (an estimated average duration of 4 days)
    • PRAM score includes assessment of oxygen saturations, suprasternal retractions, scalene muscle contraction, air entry and wheezing.

Secondary Measures

  • Intubation and complication rates
    • Time Frame: Patients will be followed for the duration of their hospital stay (an estimated average of 4 days) with data collection relative to this outcome on a daily basis
    • Number of children in each arm requiring intubation and mechanical ventilation, and experiencing significant treatment-related side effects
  • Hospital re-admission
    • Time Frame: Within 48 hours of initial hospital discharge
    • Number of children in each arm failing initial hospital discharge and requiring re-admission within 48 hours
  • Inhaled bronchodilator utilization
    • Time Frame: Patients will be followed for the duration of their hospital stay (an estimated average of 4 days) with data collection relative to this outcome on a daily basis
    • Comparison of the median daily dose of inhaled salbutamol received by children in each arm,
  • Intravenous bronchodilator utilization
    • Time Frame: Patients will be followed for the duration of their hospital stay (an estimated average of 4 days) with data collection relative to this outcome on a daily basis
    • Comparison of the total number of hours of intravenous bronchodilator infusions received by children in each arm
  • Length of hospital stay
    • Time Frame: Length of stay will be calculated at the time of each child’s hospital discharge (estimated 4 days after hospital admission and recruitment to study)
    • Duration of time from hospital admission to the patient meeting hospital discharge criteria

Participating in This Clinical Trial

Inclusion Criteria

  • 2-18 years old – Admitted to BC Children's Hospital with a clinical diagnosis of an acute asthma exacerbation – PRAM score of >3 following initial treatment with three rounds of inhaled salbutamol and ipratropium bromide, and one dose of systemic steroid – Parents willing and able to sign consent – Children over the age of 6 willing to provide assent Exclusion Criteria:

  • Clinical suspicion of co-existing bacterial pneumonia: focal crackles or bronchial breathing, and/or major chest x-ray findings – Impending respiratory failure at presentation requiring direct PICU admission – Receiving maintenance dose of oral steroid at time of hospital admission – Any contraindication to BiPAP use including altered mental status, recent bowel surgery, intractable vomiting, or inability to protect airway – Current tracheostomy, home ventilation (IPPV or NIPPV) or home oxygen requirement – History of congenital heart disease or chronic respiratory disease (including bronchopulmonary dysplasia, cystic fibrosis, pulmonary hypertension) – Craniofacial abnormality precluding the use of a tight fitting facial mask

Gender Eligibility: All

Minimum Age: 2 Years

Maximum Age: 18 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of British Columbia
  • Provider of Information About this Clinical Study
    • Principal Investigator: Michael Seear, Principle Investigator – University of British Columbia
  • Overall Official(s)
    • Michael Seear, MD, Principal Investigator, University of British Columbia

References

Martinez FD, Vercelli D. Asthma. Lancet. 2013 Oct 19;382(9901):1360-72. doi: 10.1016/S0140-6736(13)61536-6. Epub 2013 Sep 13.

Papiris SA, Manali ED, Kolilekas L, Triantafillidou C, Tsangaris I. Acute severe asthma: new approaches to assessment and treatment. Drugs. 2009;69(17):2363-91. doi: 10.2165/11319930-000000000-00000.

Soroksky A, Klinowski E, Ilgyev E, Mizrachi A, Miller A, Ben Yehuda TM, Shpirer I, Leonov Y. Noninvasive positive pressure ventilation in acute asthmatic attack. Eur Respir Rev. 2010 Mar;19(115):39-45. doi: 10.1183/09059180.00006109.

Meduri GU, Cook TR, Turner RE, Cohen M, Leeper KV. Noninvasive positive pressure ventilation in status asthmaticus. Chest. 1996 Sep;110(3):767-74. doi: 10.1378/chest.110.3.767.

Thill PJ, McGuire JK, Baden HP, Green TP, Checchia PA. Noninvasive positive-pressure ventilation in children with lower airway obstruction. Pediatr Crit Care Med. 2004 Jul;5(4):337-42. doi: 10.1097/01.pcc.0000128670.36435.83. Erratum In: Pediatr Crit Care Med. 2004 Nov;5(6):590.

Basnet S, Mander G, Andoh J, Klaska H, Verhulst S, Koirala J. Safety, efficacy, and tolerability of early initiation of noninvasive positive pressure ventilation in pediatric patients admitted with status asthmaticus: a pilot study. Pediatr Crit Care Med. 2012 Jul;13(4):393-8. doi: 10.1097/PCC.0b013e318238b07a.

Ducharme FM, Chalut D, Plotnick L, Savdie C, Kudirka D, Zhang X, Meng L, McGillivray D. The Pediatric Respiratory Assessment Measure: a valid clinical score for assessing acute asthma severity from toddlers to teenagers. J Pediatr. 2008 Apr;152(4):476-80, 480.e1. doi: 10.1016/j.jpeds.2007.08.034. Epub 2007 Oct 31.

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