Childhood Asthma Research and Education (CARE) Network Trial - Acute Intervention Management Strategies (AIMS)

Not Applicable

Completed

• Conditions: Asthma; Lung Diseases
• Interventions: Drug: Inhaled Corticosteroid (Budesonide); Drug: Leukotriene Receptor Antagonist (Montelukast Sodium); Drug: Inhaled Albuterol

• Registration Number: NCT00319488
• Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Brief Summary

This study will determine the effectiveness of initiating a high-dose inhaled corticosteroid (ICS) or a leukotriene receptor antagonist (LTRA) in addition to an inhaled beta2-agonist (albuterol) at the onset of respiratory tract illness (RTI)-associated symptoms in increasing episode-free days among young children with recurrent severe wheezing.

Detailed Description

Acute Intervention Management Strategies (AIMS) is a randomized, double-blind, double-dummy, placebo-controlled parallel comparison study that will compare the effectiveness of three treatments, when given at the onset of RTI-associated symptoms, in increasing the proportion of symptom-free days over the entire treatment period of the 5- to 9-month study. There will be a 2-week period to qualify and characterize participants, who at that time will have no lower respiratory tract symptoms other than mild cough. A total of 244 participants will be randomized to one of three treatment groups and followed for the remainder of the fall-winter-early spring season. Participants will receive one of the following treatment regimens for 7 days, at the first sign of RTI-associated symptoms: 1) active ICS plus placebo LTRA plus albuterol inhalation treatments four times daily; 2) active LTRA plus placebo ICS plus albuterol inhalation treatment four times daily; or 3) placebo ICS plus placebo LTRA plus albuterol inhalation treatments four times daily.

Study Timeline

• Study Start: 2004-02
• Study First Submitted: 2006-04-27
• Study First Submitted QC: 2006-04-27
• Study First Posted: 2006-04-27
• Primary Completion: 2006-11
• Study Completion: 2006-11
• Status Verified: 2012-04
• Last Update Submitted: 2016-07-28
• Last Update Posted: 2016-07-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 238

Inclusion Criteria

• Recurrent episodes (at least two) of wheezing in the context of a RTI, at least one of which must be documented by a health care provider (parental report) over the 12 months prior to study entry, and of which one episode must have occurred within 6 months prior to study entry

• Either two episodes of '1,' OR two episodes of '2,' OR one episode of '1' AND one episode of '2,' defined by the following:

  1. Urgent care visit for acute wheezing (emergency department, urgent care center, or unscheduled primary care physician office visit), which required treatment with a bronchodilator, within 12 months prior to study entry
  2. Episode of wheezing within 12 months prior to study entry, which required treatment with oral corticosteroids not associated with a visit to a health care provider, urgent care center, emergency department, or hospital

• Immunizations are up to date, including varicella (unless the patient has already had clinical varicella)

• Willingness to provide informed consent by patient's parent or guardian

Exclusion Criteria

• Use of more than six courses of systemic corticosteroids during the 12 months prior to study entry
• More than two hospitalizations for wheezing illnesses within 12 months prior to study entry
• Use of long-term controller medications for asthma (including inhaled corticosteroids, leukotriene modifiers, cromolyn/nedocromil, or theophylline) for 4 or more months (cumulative use) within 1 year prior to study entry
• Any use of long-term controller medications for asthma (including corticosteroids [inhaled or oral], leukotriene modifiers, cromolyn/nedocromil, or theophylline) within the 2 weeks prior to the enrollment visit
• Current treatment with antibiotics for diagnosed sinus disease
• Contraindication of use of systemic corticosteroids
• Prematurity (defined as birth before 36 weeks gestational age)
• Presence of lung disease other than asthma (e.g., cystic fibrosis and BPD)
• Presence of other significant medical illnesses (e.g., cardiac, liver, gastrointestinal, or endocrine disease) that would place the patient at increased risk
• Gastroesophageal reflux under medical therapy
• Immunodeficiency disorders
• History of respiratory failure requiring mechanical ventilation
• History of hypoxic seizure
• Inability to cooperate with nebulization therapy
• Inability to ingest the study drugs
• History of significant adverse reaction to any study medication ingredient
• Current participation, or participation in the month prior to study entry, in another investigational drug study
• Evidence that the family may be unreliable, nonadherent, or likely to move from the clinical center area before study completion
• Persistent symptomatic asthma, as defined as experiencing symptoms (i.e., nocturnal cough, daytime cough, wheezing, difficulty breathing, or symptoms interfering with activities) and/or requiring albuterol use on average 4 or more days per week in the 2-week observation period prior to the randomization visit
• The following scores, based on a 5-point scale with 5 representing very severe symptoms (measured at randomization visit): score equal to or greater than one for albuterol use, wheezing, difficulty breathing, nighttime cough, and asthma symptoms interfering with activities; score greater than 2 for daytime cough on an average of 4 or more days/week during the 2-week observation period
• Failure to complete diary cards at expected levels (at least 80% of days) during the observation period
• Use of long-term controller medications for asthma (e.g., corticosteroids [inhaled or oral], leukotriene modifiers, cromolyn/nedocromil, or theophylline) during the 2-week observation period

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Inhaled Corticosteroid (Budesonide)	Active ICS plus placebo LTRA plus albuterol inhalation treatments four times daily
1	Inhaled Albuterol	Active ICS plus placebo LTRA plus albuterol inhalation treatments four times daily
2	Leukotriene Receptor Antagonist (Montelukast Sodium)	Active LTRA plus placebo ICS plus albuterol inhalation treatment four times daily
2	Inhaled Albuterol	Active LTRA plus placebo ICS plus albuterol inhalation treatment four times daily
3	Inhaled Albuterol	Placebo ICS plus placebo LTRA plus albuterol inhalation treatments four times daily

Primary Outcome Measures

Name	Time	Method
Proportion of episode-free days as determined by diary cards	Measured over 12-month follow-up period

Secondary Outcome Measures

Name	Time	Method
Time to initiation of first course of oral corticosteroids	Measured at Weeks 2, 4, 10, 12, 18, 20, 26, 28, 34, 36, 42, 44, 50, and 52 after randomization
Total number of courses of oral corticosteroids	Measured at Weeks 2, 4, 10, 12, 18, 20, 26, 28, 34, 36, 42, 44, 50, and 52 after randomization
Duration and severity of lower respiratory tract symptoms	Measured at Weeks 2, 4, 10, 12, 18, 20, 26, 28, 34, 36, 42, 44, 50, and 52 after randomization
Number of wheezing episodes	Measured at Weeks 2, 4, 10, 12, 18, 20, 26, 28, 34, 36, 42, 44, 50, and 52 after randomization
Time to treatment failure	Measured at Weeks 2, 4, 10, 12, 18, 20, 26, 28, 34, 36, 42, 44, 50, and 52 after randomization
Measures of patient and family morbidity	Measured at Weeks 2, 4, 10, 12, 18, 20, 26, 28, 34, 36, 42, 44, 50, and 52 after randomization
Number of unscheduled visits for acute wheezing episodes	Measured at Weeks 2, 4, 10, 12, 18, 20, 26, 28, 34, 36, 42, 44, 50, and 52 after randomization
Linear growth	Measured at Weeks 2, 4, 10, 12, 18, 20, 26, 28, 34, 36, 42, 44, 50, and 52 after randomization

Trial Locations

Locations (6)

Dept. of Health Evaluation Sciences, Penn State College of Medicine; 🇺🇸 Hershey, Pennsylvania, United States

UCSD School of Medicine; 🇺🇸 LaJolla, California, United States

National Jewish Medical and Research Center; 🇺🇸 Denver, Colorado, United States

University of Wisconsin - Madison; 🇺🇸 Madison, Wisconsin, United States

Washington University School of Medicine Patient Oriented Research Unit; 🇺🇸 St. Louis, Missouri, United States

University of Arizona, College of Medicine; 🇺🇸 Tucson, Arizona, United States