Non-invasive Ventilation vs. Standard Therapy for Children Hospitalized With an Acute Exacerbation of Asthma

Study Overview
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Brief Summary
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Acute asthma produces greatly increased work of breathing and increased oxygen requirement secondary to bronchial narrowing and airway obstruction by inflammatory secretions. There is growing evidence that non-invasive ventilation can reverse these processes more efficiently than conventional asthma therapy. Surprisingly, there have not yet been any large scale prospective controlled studies to investigate this hypothesis, (either in adults or children). Consequently, the aim of this study is to determine if the use of non-invasive positive airway pressure, for children admitted to hospital with an acute exacerbation of asthma, reduces their work of breathing, need for adjunctive medications, and shortens the length of hospital stay, compared to current standard therapy.

Detailed Description
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The aim of the study is to determine if the use of NIV, for children admitted to hospital with an acute exacerbation of asthma, reduces their work of breathing, need for adjunctive medication, length of hospital stay, and need for intubation and mechanical ventilation. Study design will be prospective, randomized and controlled. The tightly fitting face mask necessary for NIV makes it impossible to make this a blinded study. The principal enrollment criteria will be children over 2 years of age presenting to the ER with acute asthma. After diagnosis, all children are treated with standard therapy (systemic steroids plus 3 doses of inhaled salbutamol and 1 dose of inhaled ipratropium over a 1 hour period then hourly salbutamol). The principal decision between discharge track and admission track will be made at 2 hours after first steroid dose. Admission criteria are based on sequential PRAM scores. After initial asthma treatment and observation in the emergency room, to determine which patients can be discharged home, those who need admission will be asked to join the study, then consented and randomized. There will be three treatment groups: BiPAP: standard steroid dose, hourly salbutamol and BiPAP at 15/5 cm H2O by face mask with rate 10 to 15/min, oxygen as needed. CPAP: standard steroid dose, hourly salbutamol and 8 to 10 cm H2O constant pressure by face mask, oxygen as needed. Conventional therapy: standard steroid dose plus hourly nebulized salbutamol, nebulized ipratropium q 6 hrly, magnesium sulphate 50 mg/kg IV (4 doses q 6 hrly), loading dose of aminophylline 6 mg/kg IV if no progress, oxygen as needed. All children will be admitted to a small 3 bed respiratory unit. They will be closely monitored and objectively scored every 4 hours using the PRAM asthma clinical severity score (Pediatric Respiratory Assessment Measure). Projected patient enrollment will be at least 30 in each arm. Estimated study duration is 6 months.

Official Title
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A Prospective Open Randomized Clinical Trial of Non-invasive Ventilation Versus Standard Therapy for Children Hospitalized With an Acute Exacerbation of Asthma.

Conditions
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Asthma Acute, Asthma in Children

Intervention / Treatment
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* Device: BiPAP
* Device: CPAP
* Drug: Ipratropium
* Drug: Magnesium Sulfate
* Drug: Aminophylline
* Drug: Standard steroid dose, hourly salbutamol, oxygen as needed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 2-18 years old Clinical diagnosis of acute asthma exacerbation (respiratory rate greater than WHO's age-dependent criteria, a history of similar previous episodes and wheezing heard on auscultation by an experienced physician) PRAM score of 8 or more after 2 hours post-steroid administration Parents willing and able to sign consent Children over the age of 6 willing to provide assent Exclusion Criteria: Clinical suspicion of bacterial pneumonia: focal crackles or bronchial breathing, and/or major chest x-ray findings. Impending respiratory failure at presentation requiring direct PICU admission Any contraindication to BiPAP use including altered mental status, recent bowel surgery, intractable vomiting, inability to protect airway, pneumothorax. Receiving maintenance dose of oral steroid at time of hospital admission History of serious unrelated illness such as congenital heart disease or bronchopulmonary dysplasia.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Conventional asthma therapy.<br>Bilevel Positive Airway Pressure group(BiPAP). BiPAP settings at 15/5 cm H2O by face mask with background rate 10 to 15/min. Standard steroid dose plus hourly salbutamol and oxygen to keep SaO2 > 92%. | Drug: Ipratropium<br>* Nebulized q6h<br>Drug: Magnesium Sulfate<br>* 50mg/kg IV, 4 doses q6h<br>Drug: Aminophylline<br>* 6mg/kg IV (if no progress)<br>Drug: Standard steroid dose, hourly salbutamol, oxygen as needed<br>* Standard common therapies for all three arms.<br>|
| Experimental: Non-invasive ventilation (CPAP).<br>Continuous Positive Airway Pressure group (CPAP). CPAP settings at 8 to 10 cm H2O. Standard steroid dose plus hourly salbutamol and oxygen to keep SaO2 > 92%. | Device: CPAP<br>* The patient breathes against a constant pressure delivered by face mask.<br>* Other names: Continuous Positive Airway Pressure;Drug: Standard steroid dose, hourly salbutamol, oxygen as needed<br>* Standard common therapies for all three arms.<br>|
| Experimental: Non-invasive ventilation (BiPAP)<br>Standard steroid dose, hourly salbutamol, oxygen as needed, nebulized ipratropium q 6 hrly, magnesium sulfate 50 mg/kg IV (4 doses q 6 hrly), loading dose of aminophylline 6 mg/kg IV if no progress. | Device: BiPAP<br>* The patient's breathing is assisted by cycling between high and low pressures at a pre-set rate.<br>* Other names: Bilevel Positive Airway Pressure;Drug: Standard steroid dose, hourly salbutamol, oxygen as needed<br>* Standard common therapies for all three arms.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to reach a PRAM score of ≤3 | PRAM score includes assessment of oxygen saturations, suprasternal retractions, scalene muscle contraction, air entry and wheezing. | Patients will be followed for the duration of their hospital stay (an estimated average duration of 4 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to room air | Time that oxygen is required | Patients will be followed for the duration of their hospital stay (an estimated average of 4 days). | 
| Total medication use per 12 hr period | Comparison of total medication use by children in each arm. | Patients will be followed for the duration of their hospital stay (an estimated average of 4 days). | 
| Numbers failing treatment and transferred to ICU | Number of patients in each group that fail treatment and require transfer to ICU | Patients will be followed for the duration of their hospital stay (an estimated average of 4 days). |