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Budesonide Inhalation Suspension for Acute Asthma in Children

Registration Number
NCT00393367
Lead Sponsor
Children's Hospital of Philadelphia
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
179
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Budesonide Inhalaiton SuspensionBudesonide inhalation suspension (0.5 mg/2mL) 2mg, albuterol (5mg/mL) 7.5 or 10mgAll 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.
Saline PlaceboAlbuterol, ipratropium bromideAll 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.
Budesonide Inhalaiton SuspensionAlbuterol, ipratropium bromideAll 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.
Saline PlaceboPrednisolone, prednisone, or methylprednisoloneAll 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.
Budesonide Inhalaiton SuspensionPrednisolone, prednisone, or methylprednisoloneAll 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.
Saline PlaceboIpratropium bromideAll 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.
Budesonide Inhalaiton SuspensionIpratropium bromideAll 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.
Primary Outcome Measures
NameTimeMethod
Median Change in Asthma Score 2 Hours After InterventionInitial asthma score minus score 2 hours after budesonide/albuterol intervention or saline placebo/albuterol comparator

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 HoursInitial asthma score minus score 2 hours after budesonide/albuterol intervention or saline placebo/albuterol comparator

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
NameTimeMethod
Relapse / Readmission Numbers.within 5 days of ED visit

Participants admitted to the hospital within 5 days of the ED visit

Number of Participants With Adverse Events (Non-serious).within 30 days of the ED visit
Serious Adverse Events0-5 days

Serious Adverse Events

Number of Patients Hospitalizedwithin 4 hours after the budesonide/albuterol intervention or saline/albuterol placebo

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 RateFrom the initial heart rate to heart rate 2 hours after intervention with budesonide/albuterol or saline/albuterol comparator

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.Initial rate, minus rate taken 2 hours after budesonide/albuterol intervention or saline/albuterol comparator

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.2 hours after treatment with either budesonide/albuterol or saline/albuterol comparator

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 CategoryFrom the initial score to 2 hours after intervention with budesonide/albuterol or saline/albuterol comparator

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 CategoryFrom the initial score to 2 hours after intervention with budesonide/albuterol or saline/albuterol comparator

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 CategoryFrom the initial score to 2 hours after intervention with budesonide/albuterol or saline/albuterol comparator

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.

Trial Locations

Locations (1)

Children's Hospital of Philadelphia Emergency Department

🇺🇸

Philadelphia, Pennsylvania, United States

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