(CARE Network Trial - Treating Children to Prevent Exacerbations of Asthma (TREXA)

• Status: Completed
• Trial end date: 2011-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Milton S. Hershey Medical Center
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Albuterol; Beclomethasone; Procaterol

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