Budesonide Inhalation Suspension for Acute Asthma in Children

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the addition of budesonide inhalation suspension (BIS) to the standard therapy of albuterol, ipratropium bromide, and systemic corticosteroids (SCS) for moderate to severe asthma flares in children reduces asthma severity more rapidly than standard therapy alone.

Detailed Description
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Context: Acute asthma is a leading cause of emergency department (ED) visits and hospitalizations. Although standard therapy for acute asthma includes systemic corticosteroids (SCS), these drugs take many hours to have an effect. Recent studies demonstrate that inhaled corticosteroids (ICS) may improve patients' asthma severity more rapidly than SCS and may decrease hospitalizations. Only a few small studies have evaluated ICS added to standard therapy for acute asthma in children. Objective: To determine if adding the nebulized steroid budesonide to standard therapy including SCS improves patients' asthma severity faster than standard therapy alone and leads to fewer hospitalizations. Study Design/Setting/Participants: A double-blind, randomized, controlled trial of budesonide inhalation suspension (BIS) versus placebo for children 2 to 18 years of age who present to a tertiary care, urban pediatric ED with a moderate to severe asthma flare. Intervention: Participants will receive standard therapy including SCS, albuterol, and ipratropium bromide and will be randomly assigned to also receive either nebulized BIS or saline. Study Measures: Differences in asthma scores, vital signs, and the need for hospitalization will be compared between treatment groups.

Official Title
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Budesonide Inhalation Suspension for Acute Asthma in Children

Conditions
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Asthma, Acute Asthma, Reactive Airway Exacerbation

Intervention / Treatment
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* Drug: Budesonide inhalation suspension (0.5 mg/2mL) 2mg, albuterol (5mg/mL) 7.5 or 10mg
* Drug: Prednisolone, prednisone, or methylprednisolone
* Drug: Albuterol, ipratropium bromide
* Drug: Ipratropium bromide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chief complaint of respiratory distress, asthma, trouble breathing, or reactive airway disease Males or females age 2 to 18 years Weight greater than or equal to 10 kilograms Two or more prior Emergency Department or primary care visits for asthma or reactive airway disease Identified in triage as either acute or critical Asthma score of 8 or greater Systemic corticosteroid prescribed in the Emergency Department English-speaking parent/guardian present Parental/guardian permission (informed consent) and if appropriate, child assent Exclusion Criteria: Systemic corticosteroid use in the last 30 days Chronic lung diseases including cystic fibrosis Sickle cell anemia Immunodeficiency Cardiac disease requiring surgery or medications Adverse drug reaction or allergy to budesonide, albuterol, ipratropium bromide, prednisone, prednisolone, or methylprednisolone Known renal or hepatic dysfunction Exposure to varicella in the last 21 days Impending respiratory failure requiring positive pressure ventilation Altered level of consciousness Suspected foreign body aspiration or croup Prior enrollment in the study

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Saline Placebo<br>All subjects will receive 3 albuterol sulfate doses, 2 ipratropium bromide doses, and systemic corticosteroids. All patients will receive both the systemic corticosteroids and one dose of a mixture of albuterol and ipratropium bromide while guardians are approached for consent. Patients randomized to this placebo comparator arm will then receive 2 nebulized albuterol doses mixed with 8mL of normal saline. Finally, all patients will receive the second nebulized ipratropium dose. | Drug: Prednisolone, prednisone, or methylprednisolone<br>* All patients are given 2mg/kg of systemic corticosteroids (max 60mg). Patients who can tolerate pills are given oral prednisone, those who cannot are given oral prednisolone, and those who cannot tolerate oral medications are given IV methylprednisolone.<br>* Other names: methylprednisolone;Drug: Albuterol, ipratropium bromide<br>* While guardians are approached for possible participation, patients are given a single nebulized dose of albuterol sulfate (5mg/mL) mixed with ipratropium bromide (500mcg/2.5mL). Patients who weigh 10-20kg receive 3.75mg of albuterol. Patients over 20kg receive 5mg of albuterol. All patients receive 500mcg of ipratropium bromide. Albuterol sulfate and ipratropium bromide are delivered by a medium volume, high flow nebulizer (AirLife Mister FinityTM)with an oxygen flow rate of 8L/min via a tight-fitting face mask.<br>* Other names: Atrovent;Drug: Ipratropium bromide<br>* 500 mcg/2.5mL. All patients receive a final dose of ipratropium bromide after the intervention or placebo. The ipratropium bromide is delivered by a medium volume, high flow nebulizer (AirLife Mister FinityTM) with an oxygen flow rate of 8L/minute via a tight-fitting face mask.<br>* Other names: Atrovent;|
| Experimental: Budesonide Inhalaiton Suspension<br>All subjects will receive 3 albuterol sulfate doses, 2 ipratropium bromide doses, and systemic corticosteroids. All patients will receive both the systemic corticosteroids and one dose of a mixture of albuterol and ipratropium bromide while guardians are approached for consent. Patients randomized to this intervention arm will then receive 2 nebulized albuterol doses mixed with 8mL of budesonide inhalation suspension (BIS). Finally, all patients will receive the second nebulized ipratropium dose. | Drug: Budesonide inhalation suspension (0.5 mg/2mL) 2mg, albuterol (5mg/mL) 7.5 or 10mg<br>* Patients randomized to budesonide inhalation suspension (BIS) receive 2 nebulized albuterol sulfate (5mg/mL) doses (2mL =10mg for patients over 20kg, 1.5mL =7.5mg for patients 10-20kg) mixed with 8mL (2mg) of BIS(0.5mg/2mL). The albuterol sulfate and BIS mixture is delivered by a medium volume, high flow nebulizer (AirLife Mister FinityTM)with an oxygen flow rate of 8L/min via a tight-fitting face mask.<br>* Other names: Albuterol;Drug: Prednisolone, prednisone, or methylprednisolone<br>* All patients are given 2mg/kg of systemic corticosteroids (max 60mg). Patients who can tolerate pills are given oral prednisone, those who cannot are given oral prednisolone, and those who cannot tolerate oral medications are given IV methylprednisolone.<br>* Other names: methylprednisolone;Drug: Albuterol, ipratropium bromide<br>* While guardians are approached for possible participation, patients are given a single nebulized dose of albuterol sulfate (5mg/mL) mixed with ipratropium bromide (500mcg/2.5mL). Patients who weigh 10-20kg receive 3.75mg of albuterol. Patients over 20kg receive 5mg of albuterol. All patients receive 500mcg of ipratropium bromide. Albuterol sulfate and ipratropium bromide are delivered by a medium volume, high flow nebulizer (AirLife Mister FinityTM)with an oxygen flow rate of 8L/min via a tight-fitting face mask.<br>* Other names: Atrovent;Drug: Ipratropium bromide<br>* 500 mcg/2.5mL. All patients receive a final dose of ipratropium bromide after the intervention or placebo. The ipratropium bromide is delivered by a medium volume, high flow nebulizer (AirLife Mister FinityTM) with an oxygen flow rate of 8L/minute via a tight-fitting face mask.<br>* Other names: Atrovent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Change in Asthma Score 2 Hours After Intervention | The scale used is the Asthma Score published by Qureshi et al. The Asthma Score ranges from a low of 5 to maximum of 15 points. One to 3 points are given for each of 5 categories: age-based respiratory rate, oxygen saturation, wheeze, retractions, and dyspnea. For category detalails, please see the Qureshi reference. Scores of 5-7 are considered mild, 8-11 moderate, and 12-15 severe. Asthma Scores are recorded prior to any intervention and at 2 hours after budesonide inhalation suspension/albuterol intervention or saline placebo/albuterol comparator. | Initial asthma score minus score 2 hours after budesonide/albuterol intervention or saline placebo/albuterol comparator | 
| Mean Change in Asthma Score at 2 Hours | The scale used is the Asthma Score published by Qureshi et al. The Asthma Score ranges from a low of 5 to maximum of 15 points. One to 3 points are given for each of 5 categories: age-based respiratory rate, oxygen saturation, wheeze, retractions, and dyspnea. For category detalails, please see the Qureshi reference. Scores of 5-7 are considered mild, 8-11 moderate, and 12-15 severe. Asthma Scores are recorded prior to any intervention and at 2 hours after budesonide inhalation suspension/albuterol intervention or saline placebo/albuterol comparator. | Initial asthma score minus score 2 hours after budesonide/albuterol intervention or saline placebo/albuterol comparator | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Hospitalized | The number of patients requiring hospital admission 4 hours after budesonide/albuterol intervention or saline/albuterol comparator. All hospitalization decisions are made at the discretion of the attending physician. | within 4 hours after the budesonide/albuterol intervention or saline/albuterol placebo | 
| Change in Mean Heart Rate | Mean of heart rate in beats per minute before treatment minus mean of heart rate 2 hours after treatment with either budesonide/albuterol or saline/albuterol | From the initial heart rate to heart rate 2 hours after intervention with budesonide/albuterol or saline/albuterol comparator | 
| Mean Change in Respiratory Rate. | Mean respiratory rate in breaths per minute before treatment minus respiratory rate 2 hours after treatment with either budesonide/albuterol or saline/albuterol comparator. | Initial rate, minus rate taken 2 hours after budesonide/albuterol intervention or saline/albuterol comparator | 
| Oxygen Saturation. | Mean oxygen saturation (non-invasive pulse-oximetry, % hemoglobin saturation) 2 hours after treatment with either budesonide/albuterol or saline/albuterol comparator minus mean oxygen saturation before treatment. | 2 hours after treatment with either budesonide/albuterol or saline/albuterol comparator | 
| Number of Subjects Remaining in the Severe Asthma Category | Of the patients who presented in the severe asthma category (Asthma Severity score of 12-15), those who remained in this category 2 hours after the budesonide/albuterol intervention or saline/albuterol comparator. | From the initial score to 2 hours after intervention with budesonide/albuterol or saline/albuterol comparator | 
| Number of Subjects Moving From the Severe Asthma to Moderate Asthma Category | Of the patients who presented in the severe asthma category (Asthma Severity score of 12-15), those who moved to the moderate category (Asthma Severity score 8-11) 2 hours after the budesonide/albuterol intervention or saline/albuterol comparator. | From the initial score to 2 hours after intervention with budesonide/albuterol or saline/albuterol comparator | 
| Number of Subjects Moving From the Severe Asthma to Mild Asthma Category | Of the patients who presented in the severe asthma category (Asthma Severity score of 12-15), those who moved to the mild category (Asthma Severity score 5-7) 2 hours after the budesonide/albuterol intervention or saline/albuterol comparator. | From the initial score to 2 hours after intervention with budesonide/albuterol or saline/albuterol comparator | 
| Relapse / Readmission Numbers. | Participants admitted to the hospital within 5 days of the ED visit | within 5 days of ED visit | 
| Number of Participants With Adverse Events (Non-serious). |  | within 30 days of the ED visit | 
| Serious Adverse Events | Serious Adverse Events | 0-5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Acute, Treatment, Children, Pediatric, Inhaled corticosteroid, Budesonide, Budesonide inhalation suspension, Asthma score, Emergency, Emergency Department, Asthma flare, Clinical trial, Randomized clinical trial, Randomized trial, Pulmonary index score, Hospitalization, Moderate asthma, Severe asthma, Mixing budesonide, Budesonide admixture, Albuterol, Continuous albuterol, Ipratropium bromide