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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Asthma, Lung Diseases

Intervention / Treatment
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* Drug: Inhaled Corticosteroid (Budesonide)
* Drug: Leukotriene Receptor Antagonist (Montelukast Sodium)
* Drug: Inhaled Albuterol


Participation Criteria
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Eligibility Criteria
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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: 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 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

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 59 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Active ICS plus placebo LTRA plus albuterol inhalation treatments four times daily | Drug: Inhaled Corticosteroid (Budesonide)<br>* Participants will receive inhaled corticosteroid for 7 days, at the first sign of RTI-associated symptoms.<br>Drug: Inhaled Albuterol<br>* All participants will receive inhaled albuterol treatments four times a day.<br>|
| Active Comparator: 2<br>Active LTRA plus placebo ICS plus albuterol inhalation treatment four times daily | Drug: Leukotriene Receptor Antagonist (Montelukast Sodium)<br>* Participants will receive leukotriene receptor antagonist for 7 days, at the first sign of RTI-associated symptoms.<br>Drug: Inhaled Albuterol<br>* All participants will receive inhaled albuterol treatments four times a day.<br>|
| Placebo Comparator: 3<br>Placebo ICS plus placebo LTRA plus albuterol inhalation treatments four times daily | Drug: Inhaled Albuterol<br>* All participants will receive inhaled albuterol treatments four times a day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of episode-free days as determined by diary cards |  | Measured over 12-month follow-up period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Wheezing, Respiratory Tract Illness