Childhood Asthma Research and Education (CARE) Network Trial - Best Add-On Therapy Giving Effective Response (BADGER)
Information source: Milton S. Hershey Medical Center
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Asthma
Intervention: fluticasone propionate + montelukast (Drug); fluticasone propionate (Drug); fluticasone propionate + salmeterol (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Milton S. Hershey Medical Center Official(s) and/or principal investigator(s): David T. Mauger, PhD, Principal Investigator, Affiliation: Penn State College of Medicine Stanley J. Szefler, MD, PhD, Principal Investigator, Affiliation: National Jewish Health Robert F. Lemanske, Jr., MD, Principal Investigator, Affiliation: University of Wisconsin, Madison Robert S. Zeiger, MD, PhD, Principal Investigator, Affiliation: Kaiser Permanente Medical Center Robert C. Strunk, MD, Principal Investigator, Affiliation: Washington University School of Medicine Fernando D. Martinez, MD, Principal Investigator, Affiliation: University of Arizona College of Medicine Lynn M. Taussig, MD, Study Chair, Affiliation: University of Denver
Summary
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.
Clinical Details
Official title: Childhood Asthma Research and Education (CARE) Network Trial - Best Add-On Therapy Giving Effective Response (BADGER)
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: 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.
Secondary outcome: Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1)Post-bronchodilator Forced FEV1 Forced Vital Capacity (FVC) FEV1/FVC Morning Peak Expiratory Flow Rate (PEFR) Evening PEFR PEFR Variability Impulse Oscillometry Methacholine PC20 Exhaled Nitric Oxide Asthma Control Test Asthma Quality of Life Time Until First Asthma Exacerbation Adverse Events
Detailed 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:
- 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.
Eligibility
Minimum age: 6 Years.
Maximum age: 18 Years.
Gender(s): Both.
Criteria:
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:
1. Naïve to controller therapy and meeting National Asthma Education and Prevention
Program (NAEPP) criteria for mild-moderate persistent asthma (symptoms at least
2 days per week and/or night-time awakenings due to asthma at least 2 nights per
month)
2. Current uncontrolled asthma (meets NAEPP criteria for mild-moderate persistent
asthma) while receiving an ICS dose greater than or equal to 200 ug per day of
fluticasone equivalent or some form of non-ICS controller therapy (e. g.,
montelukast, theophylline, cromolyn)
3. Asthma is currently under control while receiving an ICS dose between 300 to 400
ug per day of fluticasone equivalent and willing to consider changing current
treatment to monotherapy with one dose of ICS (current standard of care)
4. Asthma is currently under control while receiving some form of combination
therapy, such as ICS less than or equal to 200 ug per day of fluticasone
equivalent in addition to a non-ICS controller therapy (e. g., LABA, montelukast,
theophylline, cromolyn), and willing to consider changing current treatment to
monotherapy with one dose of ICS (current standard of care)
- 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:
1) On average, on more than 2 days per week, one or all of the following:
1. Diary-reported symptoms
2. The use of inhaled bronchodilator (not including pre-exercise)
3. Peak flows in the yellow zone (less than 80% of post bronchodilator PEF value
obtained at study visit 1) OR
- 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:
1. Oral - Use within 2 weeks of the screening visit
2. Injectable - Use within 2 weeks of the screening visit
3. Nasal - May be used at any time during the study at the discretion of the study
investigator or primary care physician
- 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
Locations and Contacts
University of Arizona College of Medicine, Tucson, Arizona 85724, United States
Kaiser Permanente Medical Center, San Diego, California 92111, United States
National Jewish Medical and Research Center, Denver, Colorado 80206, United States
Washington University School of Medicine, St. Louis, Missouri 63110, United States
University of Wisconsin - Madison, Madison, Wisconsin 53792, United States
Additional Information
Click here for the Childhood Asthma Research and Education (CARE) Network web site
Starting date: March 2007
Last updated: February 24, 2013
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