Budesonide Inhalation Suspension for Acute Asthma in Children

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT00393367
First received: October 25, 2006
Last updated: August 6, 2012
Last verified: August 2012
  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 4

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:


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 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

  • Number of Participants With 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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
Responsible Party: 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: August 6, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Children's Hospital of Philadelphia:
Asthma
Asthma score
Asthma flare
Moderate asthma
Severe asthma
Acute
Treatment
Children
Pediatric
Inhaled corticosteroid
Budesonide
Budesonide inhalation suspension
Emergency
Emergency Department
Clinical trial
Randomized clinical trial
Randomized trial
Pulmonary index score
Hospitalization
Mixing budesonide
Budesonide admixture
Albuterol
Continuous albuterol
Ipratropium bromide

Additional relevant MeSH terms:
Asthma
Respiratory Aspiration
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Respiration Disorders
Pathologic Processes
Methylprednisolone acetate
Prednisolone acetate
Prednisone
Budesonide
Prednisolone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone hemisuccinate
Prednisolone phosphate
Albuterol
Ipratropium
Bromides
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on September 16, 2014