Budesonide Inhalation Suspension for Acute Asthma in Children - Full Text View

Sponsor:	Children's Hospital of Philadelphia
Information provided by:	Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:	NCT00393367

Purpose

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.

Condition	Intervention	Phase
Asthma Acute Asthma Reactive Airway Exacerbation	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	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Budesonide Inhalation Suspension for Acute Asthma in Children

Resource links provided by NLM:

MedlinePlus related topics: Asthma Oxygen Therapy

Drug Information available for: Prednisolone Prednisolone acetate Prednisone Depo-medrol Albuterol Ipratropium bromide Levalbuterol hydrochloride Albuterol sulfate Budesonide Ipratropium Medrol veriderm Methylprednisolone Levalbuterol tartrate Prednisolone sodium phosphate Prednisolone Sodium Succinate Methylprednisolone Sodium Succinate Methylprednisolone hemisuccinate 6-Methylprednisolone Corticosteroids

U.S. FDA Resources

Further study details as provided by Children's Hospital of Philadelphia:

Primary Outcome Measures:

Median Change in Asthma Score 2 Hours After Intervention [ Time Frame: Initial asthma score minus score 2 hours after budesonide/albuterol intervention or saline placebo/albuterol comparator ] [ Designated as safety issue: No ]
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.
Mean Change in Asthma Score at 2 Hours [ Time Frame: Initial asthma score minus score 2 hours after budesonide/albuterol intervention or saline placebo/albuterol comparator ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Number of Patients Hospitalized [ Time Frame: within 4 hours after the budesonide/albuterol intervention or saline/albuterol placebo ] [ Designated as safety issue: No ]
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.
Change in Mean Heart Rate [ Time Frame: From the initial heart rate to heart rate 2 hours after intervention with budesonide/albuterol or saline/albuterol comparator ] [ Designated as safety issue: No ]
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
Mean or Change in Respiratory Rate. [ Time Frame: Initial rate, minus rate taken 2 hours after budesonide/albuterol intervention or saline/albuterol comparator ] [ Designated as safety issue: No ]
Mean respiratory rate in breaths per minute before treatment minus respiratory rate 2 hours after treatment with either budesonide/albuterol or saline/albuterol comparator.
Oxygen Saturation. [ Time Frame: 2 hours after treatment with either budesonide/albuterol or saline/albuterol comparator ] [ Designated as safety issue: No ]
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.
Number of Subjects Remaining in the Severe Asthma Category [ Time Frame: From the initial score to 2 hours after intervention with budesonide/albuterol or saline/albuterol comparator ] [ Designated as safety issue: No ]
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.
Number of Subjects Moving From the Severe Asthma to Moderate Asthma Category [ Time Frame: From the initial score to 2 hours after intervention with budesonide/albuterol or saline/albuterol comparator ] [ Designated as safety issue: No ]
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.
Number of Subjects Moving From the Severe Asthma to Mild Asthma Category [ Time Frame: From the initial score to 2 hours after intervention with budesonide/albuterol or saline/albuterol comparator ] [ Designated as safety issue: No ]
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.
Relapse / Readmission Numbers. [ Time Frame: within 5 days of ED visit ] [ Designated as safety issue: No ]
Participants admitted to the hospital within 5 days of the ED visit
Adverse Events (Non-serious). [ Time Frame: within 30 days of the ED visit ] [ Designated as safety issue: Yes ]
Serious Adverse Events [ Time Frame: 0-5 days ] [ Designated as safety issue: Yes ]
Serious Adverse Events

Enrollment:	179
Study Start Date:	December 2006
Study Completion Date:	November 2007
Primary Completion Date:	November 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 prednisone methylprednisolone 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: Albuterol Atrovent 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 Name: 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: 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 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 prednisone methylprednisolone 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: Albuterol Atrovent 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 Name: Atrovent

Arms

Assigned Interventions

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
prednisone
methylprednisolone

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:

Albuterol
Atrovent

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 Name: 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: 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

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
prednisone
methylprednisolone

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:

Albuterol
Atrovent

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 Name: Atrovent

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.

Eligibility

Ages Eligible for Study:	2 Years to 18 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00393367

Locations

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

Sponsors and Collaborators

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

More Information

Publications:

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. Review.

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.

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.

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.

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.

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.

Responsible Party:	Cynthia J. Mollen, MD, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:	NCT00393367 History of Changes
Other Study ID Numbers:	2006-8-4875
Study First Received:	October 25, 2006
Results First Received:	April 9, 2010
Last Updated:	June 24, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by Children's Hospital of Philadelphia:

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

Additional relevant MeSH terms:

Respiratory Aspiration
Asthma
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Bronchial Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Albuterol
Ipratropium

Budesonide
Methylprednisolone
Bromides
Methylprednisolone Hemisuccinate
Methylprednisolone acetate
Prednisolone acetate
Prednisolone
Prednisone
Prednisolone phosphate
Tocolytic Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Adrenergic beta-2 Receptor Agonists

ClinicalTrials.gov processed this record on February 09, 2012