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About
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.
Full description
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:
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.
Enrollment
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Volunteers
Inclusion criteria
Able to perform reproducible spirometry according to American Thoracic Society (ATS) criteria
History of asthma symptoms (e.g., cough, wheezing, shortness of breath) and meets at least one of the following criteria:
FEV1 reversibility of at least 12% following bronchodilator administration (4 puffs) at study visit 1. Individuals will need to hold albuterol, montelukast, theophylline, ipratropium bromide (or other anticholinergics) and LABAs per study instructions prior to reversibility testing. If an individual is receiving these types of medications prior to study visit 1, he/she may be brought back to the clinical center within 1 week following appropriate medication withholding to attempt qualification by reversibility criteria. If the individual does not meet this requirement, they may qualify for enrollment if their PC20 methacholine FEV1 is less than or equal to 12.5 mg/ml at the time of randomization. If FEV1 is less than 70%, thus precluding the methacholine challenge at this visit, then completion of the visit will be postponed several days and an additional attempt to obtain a methacholine challenge test will be made. If the methacholine challenge still cannot be performed, an individual may still qualify by reversibility criteria at this visit.
History of clinical varicella or varicella vaccine; individuals needing the vaccine may receive it from their primary care physician prior to study entry
Ability of parent to provide informed consent; verbal assent must be obtained from children less than 7 years of age and written assent must be obtained from children between 7 and 18 years of age
If female, willing to use an effective form of contraception
Prior to being randomly assigned to a treatment group, participants must meet the following criteria to remain in the study:
Lack of acceptable asthma control during the 8-week screening period as defined by the following criteria:
On average, more than 1 night-time awakening due to asthma, during each 2-week period
Exclusion criteria
Corticosteroid treatment for any condition prior to study entry within the following defined timepoints:
Current or prior use of medications known to significantly interact with corticosteroid disposition (within a 2-week period of study visit 1), including but not limited to carbamazepine, erythromycin or other macrolide antibiotics, phenobarbital, phenytoin, rifampin, or ketoconazole
Pre-bronchodilator FEV1 less than 60% predicted at study visit 1
More than three hospitalizations for asthma in the year prior to study entry
Presence of chronic or active lung disease other than asthma
Significant medical illness other than asthma, including thyroid disease, diabetes mellitus, Cushing's disease, Addison's disease, hepatic disease, or concurrent medical problems that could require oral corticosteroids during the study or would place the participant at increased risk while participating in the study
History of cataracts, glaucoma, or any other medical disorder associated with an adverse effect to corticosteroids
Gastroesophageal reflux symptoms not controlled by standard medical therapy
History of significant asthma exacerbation within 2 weeks of study visit 1 or more than 5 courses of systemic corticosteroids in the year prior to study entry
History of a life-threatening asthma exacerbation requiring intubation, mechanical ventilation, or resulting in a hypoxic seizure within the 5 years prior to study entry
History of adverse reactions to ICS, LTRA, or LABA preparations or any of their ingredients
Receiving hyposensitization therapy other than an established maintenance regimen (i.e., continuous regimen for at least 3 months prior to study entry)
Pregnant or breastfeeding
Inability to perform study procedures
Refusal to consent to a genotype evaluation
Inability of the child to ingest the study drug
Cigarette smoking or smokeless tobacco use in the year prior to study entry
Current participation or participation in the month prior to study entry in another investigational drug trial
Evidence that the family may be unreliable or nonadherent, or may move from the clinical center area before study completion
Primary purpose
Allocation
Interventional model
Masking
182 participants in 6 patient groups
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Data sourced from clinicaltrials.gov
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