Asthma is a common, serious illness among children in the United States. While a low dose of inhaled corticosteroids (ICS) may effectively control symptoms, some children may require additional medications to maintain adequate asthma control. This study compares the effectiveness of a higher dose of ICS, ICS combined with a long-acting beta-agonist (LABA) medication, and ICS combined with a leukotriene receptor antagonist (LTRA) medication at reducing the impact and severity of asthma exacerbations that occur in children with mild to moderate persistent asthma.
Almost 9 million children in the United States have asthma, and it is a leading cause of hospitalizations and school absenteeism. Common asthma symptoms include wheezing, shortness of breath, chest tightness, and coughing. While there is no cure for asthma, most children who receive proper treatment are able to control symptoms and lead a normal life. Low doses of ICS are commonly prescribed to prevent symptoms and keep asthma under control. While this is usually sufficient to prevent asthma attacks, some children do not respond well to low dose ICS alone. For these children, their asthma symptoms may be more effectively controlled by either receiving a higher dose of ICS or receiving LABA or LTRA medications in combination with a low dose of ICS. Both LABA and LTRA medications are used to help control moderate to severe asthma. The purpose of this study is to compare the effectiveness of a high dose of ICS versus a low dose of ICS plus either LABA or LTRA medication at improving asthma control and reducing the severity of symptoms that occur in children with mild to moderate persistent asthma. This study began with an 8-week screening period during which participants were monitored while they used an inhaler with a low dose of ICS medication. During this time, participants also attended one or two study visits. At each visit, participants underwent a physical examination, exhaled nitric oxide analysis, and lung function and airway pressure testing. After enrollment criteria were met, participants underwent these same evaluations again, and they completed questionnaires to assess asthma control, quality of life, and home environmental factors. Blood was collected and a methacholine challenge test was completed, which artificially triggers an asthma attack to determine the severity of an individual's asthma. Participants then were randomly assigned to one of six treatment sequences, each of which includes the following three regimens in a different order: * Low dose of ICS and salmeterol, a LABA medication * Low dose of ICS and montelukast, a LTRA medication * Double dose of ICS Each treatment period lasted 16 weeks, with study visits occurring weekly. A physical examination, blood collection, lung function and airway pressure testing, a methacholine challenge test, and questionnaires occurred at selected visits. Throughout the study, participants recorded asthma symptoms, peak expiratory flow rates, and rescue medication usage in a daily diary. The entire length of the study did not exceed 56 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
182
Dry-powder inhaler fluticasone 100 mcg bid (Flovent Diskus®, GlaxoSmithKline) plus Montelukast 5 or 10 mg qd (Singulair®, Merck)
Dry-powder inhaler fluticasone 250 mcg bid (Flovent Diskus®, GlaxoSmithKline)
Dry-powder inhaler fluticasone + salmeterol combination 100 mcg/50 mcg bid (Advair Diskus®, GlaxoSmithKline)
University of Arizona College of Medicine
Tucson, Arizona, United States
Kaiser Permanente Medical Center
San Diego, California, United States
National Jewish Medical and Research Center
Denver, Colorado, United States
Washington University School of Medicine
St Louis, Missouri, United States
University of Wisconsin - Madison
Madison, Wisconsin, United States
The Number of Participants With a Differential Response to the Three Step-up Therapies Based on Fixed Threshold Criteria for the Following Three Asthma Control Measures: Use of Oral Prednisone for Acute Asthma Exacerbations, Asthma Control Days and FEV1.
One treatment period was ranked as better than another if the total amount of prednisone received during the period was at least 180 mg less, if the number of annualized asthma-control days during the final 12 weeks of the period was increased by at least 31 days, or if the FEV1 at the end of the period was at least 5% higher. If the prednisone threshold was met, then we ignored the number of asthmacontrol days and the FEV1. If the threshold for asthma-control days was met, then we ignored the FEV1. Otherwise, the order of response was determined by the FEV1.
Time frame: Measured during the last 12 weeks of each 16-week treatment period
Change From Baseline in the Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) % Predicted
Time frame: Measured during the last 12 weeks of each 16-week treatment period
Change From Baseline in the Post-bronchodilator FEV1 Percent Predicted
Time frame: Measured during the last 12 weeks of each 16-week treatment period
Change From Baseline in the Pre-bronchodilator Forced Vital Capacity (FVC) % Predicted
Time frame: Measured during the last 12 weeks of each 16-week treatment period
Change From Baseline in the Pre-bronchodilator FEV1/FVC Ratio
Time frame: Measured during the last 12 weeks of each 16-week treatment period
Change From Baseline in the Morning Peak Expiratory Flow Rate (PEFR) % Predicted
Time frame: Measured during the last 12 weeks of each 16-week treatment period
Change From Baseline in the Evening Peak Expiratory Flow Rate (PEFR) % Predicted
Time frame: Measured during the last 12 weeks of each 16-week treatment period
Change From Baseline in the Peak Expiratory Flow Rate (PEFR) Variability
PEFR variability is calculated as 100% times the difference between the evening and morning PEFR values, divided by the average of the evening and morning PEFR values, i.e., PEFR variability = 100% x (morning PEFR - evening PEFR)/((morning PEFR + evening PEFR)/2)
Time frame: Measured during the last 12 weeks of each 16-week treatment period
Change From Baseline in the Impulse Oscillometry Resistance at 5 Hertz
Change from baseline in the impulse oscillometry resistance at 5 Hertz, measured in kiloPascals per liters per second
Time frame: Measured during the last 12 weeks of each 16-week treatment period
Change From Baseline in the Logarithm Base 2 of the Methacholine PC20
The methacholine PC20 is the concentration of methacholine that causes a 20% decrease in the pre-bronchodilator FEV1. The logarithm base 2 transformation converts the PC20 into doubling dilutions.
Time frame: Measured during the last 12 weeks of each 16-week treatment period
Change From Baseline in the Natural Logarithm of Exhaled Nitric Oxide (eNO)
Time frame: Measured during the last 12 weeks of each 16-week treatment period
Change From Baseline in the Asthma Control Test (ACT)
The ACT consists of five items, each scored as 1 (worst) to 5 (best). The five items are averaged.
Time frame: Measured during the last 12 weeks of each 16-week treatment period
Change From Baseline in Asthma Quality of Life
Asthma quality of life is measured as the average of 23 questions, each of which is scored from 1 (worse) to 7 (best)
Time frame: Measured during the last 12 weeks of each 16-week treatment period
Number of Participants With Asthma Exacerbations
An asthma exacerbation was defined as the administration of a course of oral/systemic prednisone for the treatment of asthma.
Time frame: Measured during the last 12 weeks of each 16-week treatment period
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