Childhood Asthma Research and Education (CARE) Network Trial - Best Add-On Therapy Giving Effective Response (BADGER)
Condition: Asthma
MeSH terms: Asthma
Intervention: fluticasone propionate + montelukast; fluticasone propionate; fluticasone propionate + salmeterol
Intervention description: 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)
Intervention MeSH terms: Fluticasone; Xhance; Salmeterol Xinafoate; Fluticasone-Salmeterol Drug Combination; Montelukast
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 182.0
Sex: All
Minimum age: 6 Years
Maximum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility 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