Budesonide Inhalation Suspension for Acute Asthma in Children

Overview

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 Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: November 2007

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.

Interventions

  • 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.
  • 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.
  • 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.
  • 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.

Arms, Groups and Cohorts

  • 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.
  • 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.

Clinical Trial Outcome Measures

Primary 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
    • 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
    • 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 Measures

  • Number of Patients Hospitalized
    • Time Frame: within 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 Rate
    • Time Frame: From 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.
    • Time Frame: 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.
    • Time Frame: 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 Category
    • Time Frame: From 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 Category
    • Time Frame: From 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 Category
    • Time Frame: From 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.
  • Relapse / Readmission Numbers.
    • Time Frame: 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).
    • Time Frame: within 30 days of the ED visit
  • Serious Adverse Events
    • Time Frame: 0-5 days
    • Serious Adverse Events

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 2 Years

Maximum Age: 18 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Children’s Hospital of Philadelphia
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Cynthia J Mollen, M.D., Principal Investigator, Children’s Hospital of Philadelphia
    • Bryan D. Upham, M.D., Study Director, University of New Mexico Children’s Hospital

References

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. Update in: Cochrane Database Syst Rev. 2012;12:CD002308.

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.

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