(CARE Network Trial - Treating Children to Prevent Exacerbations of Asthma (TREXA)
Condition: Asthma
MeSH terms: Asthma
Intervention: Beclomethasone dipropionate; Beclomethasone dipropionate; Albuterol sulfate
Intervention description: Beclomethasone dipropionate HFA (QVAR® 40 mcg Inhalation Aerosol) one puff bid; Beclomethasone dipropionate HFA (QVAR® 40 mcg Inhalation Aerosol) rescue puffs as needed; Albuterol sulfate HFA (ProAir® 90 mcg Inhalation Aerosol) rescue puffs as needed
Intervention MeSH terms: Beclomethasone; Albuterol
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 288.0
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. It can be
      effectively controlled through the use of preventative medications and "rescue" medications,
      which are used to control symptoms. This study will evaluate the impact and severity of
      asthma exacerbations that occur in children with mild persistent asthma who are receiving
      various combinations of medications for daily and rescue use.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Able to perform reproducible spirometry according to American Thoracic Society (ATS)
             criteria

          -  History of asthma symptoms that are adequately controlled in the 4 weeks prior to
             study entry, and meets at least one of the following criteria:

               1. History of mild persistent asthma symptoms (on average greater than 2 days per
                  week with symptoms or albuterol use for symptoms or greater than 2 night-time
                  awakenings per month during the year prior to study entry) and has been treated
                  with a single-controller inhaled corticosteroid (ICS) dose less than or equal to
                  160 mcg per day of a beclomethasone-equivalent or a leukotriene receptor
                  antagonist (LTRA) (in an age-appropriate dose) for the 4 weeks prior to study
                  entry; individuals treated with a combination controller therapy (e.g. ICS+LTRA
                  or ICS+long-acting beta-agonist (LABA)) in the past 8 weeks will not be eligible

               2. Not currently being treated with ICS, a history of mild persistent asthma, and 1
                  to 2 exacerbations in the year prior to study entry (but none in the 3 months
                  prior to study entry)

          -  Forced expiratory volume in one second (FEV1) reversibility of greater than or equal
             to 12% following bronchodilator administration (4 puffs); individuals who do not meet
             this requirement may qualify for enrollment if their methacholine provocative
             concentration at 20% (PC20) is less than or equal to 12.5 milligrams per milliliter
             (mg/ml)

          -  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

        Participants will be eligible for the 44 weeks of treatment if, after the 4-week screening
        period, their asthma remains controlled, and they demonstrate at least 80% predicted
        pre-bronchodilator FEV1. Participants must meet ALL of the criteria stated below during the
        8-week screening period to continue in the study:

          -  Meets the definition of acceptable asthma control, which is NOT having one or more of
             the following during ANY 2-week period:

               1. On average, on more than 2 days per week, experiences one or more 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 personal best defined as
                       based on peak expiratory flow (PEF) value obtained at study visit 1

               2. More than 1 night-time awakening due to asthma

          -  Demonstrates adherence with taking study medications (at least 75% of scheduled
             doses), rescue medications (using both rescue inhalers for at least 75% of rescue
             doses), and completing patient diaries (at least 75% of days)

          -  Pre-bronchodilator FEV1 greater than or equal to 80% predicted at study visits 2 and 3

          -  Agrees to not use a spacer with beclomethasone/placebo study and rescue medications

        NOTE: In January 2008, the Data and Safety Monitoring Board (DSMB) approved changes in the
        TREXA eligibility criteria, by which neither FEV1 reversibility ≥ 12% nor a participant's
        methacholine PC20 ≤ 12.5 mg/ml were required for randomization.

        Exclusion Criteria:

          -  Corticosteroid treatment for any condition prior to study entry within the following
             defined timepoints:

               1. Oral - Use within 2-week period of the screening visit

               2. Injectable - Use within 2-week period of the screening visit

               3. Nasal corticosteroids 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

          -  Any hospitalization 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

          -  History of cataracts, glaucoma, or any other medical disorder associated with an
             adverse effect to corticosteroids

          -  Any asthma exacerbation in the past 3 months or more than 2 in the past year.

          -  History of a life-threatening asthma exacerbation requiring intubation, mechanical
             ventilation, or resulting in a hypoxic seizure

          -  History of adverse reactions to ICS preparations or any of its ingredients

          -  Receiving hyposensitization therapy other than an established maintenance regimen
             (continuous regimen for at least 3 months)

          -  Pregnant or breastfeeding

          -  Cigarette smoking or smokeless tobacco use in the year prior to study entry

          -  Refusal to consent to a genotype evaluation

          -  Current participation or participation within 1 month of 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