Budesonide Inhalation Suspension for Acute Asthma in Children

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.

Study Overview

• Status: Completed
• Conditions: Asthma; Acute Asthma; Reactive Airway Exacerbation
• Intervention / Treatment: Drug: Prednisolone, prednisone, or methylprednisolone; Drug: Albuterol, ipratropium bromide; Drug: Ipratropium bromide; Drug: Budesonide inhalation suspension (0.5 mg/2mL) 2mg, albuterol (5mg/mL) 7.5 or 10mg

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 179
• Phase: Phase 4

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Saline Placebo; 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; 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.; Other Names: Prednisolone; methylprednisolone; prednisone; Drug: Albuterol, ipratropium bromide; 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.; Other Names: Atrovent; Albuterol; Drug: Ipratropium bromide; 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.; Other Names: Atrovent
Experimental: Budesonide Inhalaiton Suspension; 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: Prednisolone, prednisone, or methylprednisolone; 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.; Other Names: Prednisolone; methylprednisolone; prednisone; Drug: Albuterol, ipratropium bromide; 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.; Other Names: Atrovent; Albuterol; Drug: Ipratropium bromide; 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.; Other Names: Atrovent; Drug: Budesonide inhalation suspension (0.5 mg/2mL) 2mg, albuterol (5mg/mL) 7.5 or 10mg; 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.; Other Names: Pulmicort; Albuterol

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Investigators: Principal Investigator: Cynthia J Mollen, M.D., Children's Hospital of Philadelphia; Study Director: Bryan D. Upham, M.D., University of New Mexico Children's Hospital

Publications and helpful links

General Publications

• Qureshi F, Pestian J, Davis P, Zaritsky A. Effect of nebulized ipratropium on the hospitalization rates of children with asthma. N Engl J Med. 1998 Oct 8;339(15):1030-5. doi: 10.1056/NEJM199810083391503.
• Edmonds ML, Camargo CA Jr, Pollack CV Jr, Rowe BH. Early use of inhaled corticosteroids in the emergency department treatment of acute asthma. Cochrane Database Syst Rev. 2003;(3):CD002308. doi: 10.1002/14651858.CD002308.
• Sung L, Osmond MH, Klassen TP. Randomized, controlled trial of inhaled budesonide as an adjunct to oral prednisone in acute asthma. Acad Emerg Med. 1998 Mar;5(3):209-13. doi: 10.1111/j.1553-2712.1998.tb02614.x.
• Devidayal, Singhi S, Kumar L, Jayshree M. Efficacy of nebulized budesonide compared to oral prednisolone in acute bronchial asthma. Acta Paediatr. 1999 Aug;88(8):835-40. doi: 10.1080/08035259950168748.
• Scarfone RJ, Loiselle JM, Wiley JF 2nd, Decker JM, Henretig FM, Joffe MD. Nebulized dexamethasone versus oral prednisone in the emergency treatment of asthmatic children. Ann Emerg Med. 1995 Oct;26(4):480-6. doi: 10.1016/s0196-0644(95)70118-4.
• Nuhoglu Y, Atas E, Nuhoglu C, Iscan M, Ozcay S. Acute effect of nebulized budesonide in asthmatic children. J Investig Allergol Clin Immunol. 2005;15(3):197-200.
• Schuh S, Reisman J, Alshehri M, Dupuis A, Corey M, Arseneault R, Alothman G, Tennis O, Canny G. A comparison of inhaled fluticasone and oral prednisone for children with severe acute asthma. N Engl J Med. 2000 Sep 7;343(10):689-94. doi: 10.1056/NEJM200009073431003.

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): November 1, 2007
• Study Completion (Actual): November 1, 2007

Study Registration Dates

• First Submitted: October 25, 2006
• First Submitted That Met QC Criteria: October 25, 2006
• First Posted (Estimate): October 27, 2006

Study Record Updates

• Last Update Posted (Estimate): August 10, 2012
• Last Update Submitted That Met QC Criteria: August 6, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: Treatment; Asthma; Randomized clinical trial; Children; Pediatric; Emergency Department; Clinical trial; Randomized trial; Emergency; Inhaled corticosteroid; Hospitalization; Acute; Budesonide; Moderate asthma; Albuterol; Severe asthma; Ipratropium bromide; Budesonide inhalation suspension; Asthma score; Asthma flare; Pulmonary index score; Mixing budesonide; Budesonide admixture; Continuous albuterol
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Immune System Diseases; Respiration Disorders; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Respiratory Aspiration; Asthma; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Adrenergic Agonists; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Budesonide; Prednisone; Albuterol; Bromides; Ipratropium
• Other Study ID Numbers: 2006-8-4875