Asthma, Lung Diseases
Conditions
Keywords
Wheezing, Respiratory Tract Illness
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.
Interventions
DRUGInhaled Corticosteroid (Budesonide)
Participants will receive inhaled corticosteroid for 7 days, at the first sign of RTI-associated symptoms.
DRUGLeukotriene Receptor Antagonist (Montelukast Sodium)
Participants will receive leukotriene receptor antagonist for 7 days, at the first sign of RTI-associated symptoms.
All participants will receive inhaled albuterol treatments four times a day.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Months to 59 Months
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of episode-free days as determined by diary cards | Measured over 12-month follow-up period |
Secondary
| Measure | Time frame |
|---|---|
| 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 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 |
| 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 |
| Time to treatment failure | Measured at Weeks 2, 4, 10, 12, 18, 20, 26, 28, 34, 36, 42, 44, 50, and 52 after randomization |
Countries
United States
Outcome results
None listed