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Childhood Asthma Research and Education (CARE) Network Trial - Treating Children to Prevent Exacerbations of Asthma (TREXA)
This study is currently recruiting participants.
Verified by National Heart, Lung, and Blood Institute (NHLBI), February 2009
First Received: October 30, 2006   Last Updated: February 11, 2009   History of Changes
Sponsored by: National Heart, Lung, and Blood Institute (NHLBI)
Information provided by: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT00394329
  Purpose

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.


Condition Intervention Phase
Asthma
Drug: Beclomethasone dipropionate
Drug: Albuterol sulfate
Phase III

MedlinePlus related topics: Asthma
Drug Information available for: Albuterol Levalbuterol hydrochloride Albuterol sulfate Procaterol hydrochloride Levalbuterol tartrate Beclomethasone Beclomethasone dipropionate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title: Childhood Asthma Research and Education (CARE) Network Trial - Treating Children to Prevent Exacerbations of Asthma (TREXA)

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:
  • Time to asthma exacerbation requiring systemic corticosteroid therapy [ Time Frame: Measured during the 44-week treatment period ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Asthma control days [ Time Frame: Measured during the 44-week treatment period ] [ Designated as safety issue: No ]
  • Albuterol use [ Time Frame: Measured during the 44-week treatment period ] [ Designated as safety issue: No ]
  • Spirometry, pre- and post-bronchodilator [ Time Frame: Measured during the 44-week treatment period ] [ Designated as safety issue: No ]
  • AM and PM peak expiratory flow rate [ Time Frame: Measured during the 44-week treatment period ] [ Designated as safety issue: No ]
  • Peak expiratory flow rate variability [ Time Frame: Measured during the 44-week treatment period ] [ Designated as safety issue: No ]
  • Impulse oscillometry [ Time Frame: Measured during the 44-week treatment period ] [ Designated as safety issue: No ]
  • Methacholine PC20 [ Time Frame: Measured during the 44-week treatment period ] [ Designated as safety issue: No ]
  • Exhaled nitric oxide [ Time Frame: Measured during the 44-week treatment period ] [ Designated as safety issue: No ]
  • Asthma-specific quality of life assessment [ Time Frame: Measured during the 44-week treatment period ] [ Designated as safety issue: No ]
  • Asthma control test [ Time Frame: Measured during the 44-week treatment period ] [ Designated as safety issue: No ]
  • Adverse events [ Time Frame: Measured during the 44-week treatment period ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 280
Study Start Date: November 2006
Estimated Study Completion Date: May 2010
Estimated Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
A: Experimental
Beclomethasone diproprionate HFA (QVAR® 40 mcg Inhalation Aerosol) one puff bid + beclomethasone diproprionate HFA (QVAR® 40 mcg Inhalation Aerosol) rescue puffs as needed + albuterol sulfate HFA (ProAir®™ 90 mcg Inhalation Aerosol) rescue puffs as needed
Drug: Beclomethasone dipropionate
Beclomethasone diproprionate HFA (QVAR® 40 mcg Inhalation Aerosol) one puff bid
Drug: Beclomethasone dipropionate
Beclomethasone diproprionate HFA (QVAR® 40 mcg Inhalation Aerosol) rescue puffs as needed
Drug: Albuterol sulfate
Albuterol sulfate HFA (ProAir® 90 mcg Inhalation Aerosol) rescue puffs as needed
B: Active Comparator
Beclomethasone diproprionate HFA (QVAR® 40 mcg Inhalation Aerosol) one puff bid + albuterol sulfate HFA (ProAir® 90 mcg Inhalation Aerosol) rescue puffs as needed
Drug: Beclomethasone dipropionate
Beclomethasone diproprionate HFA (QVAR® 40 mcg Inhalation Aerosol) one puff bid
Drug: Albuterol sulfate
Albuterol sulfate HFA (ProAir® 90 mcg Inhalation Aerosol) rescue puffs as needed
C: Experimental
Beclomethasone diproprionate HFA (QVAR® 40 mcg Inhalation Aerosol) rescue puffs as needed + albuterol sulfate HFA (ProAir® 90 mcg Inhalation Aerosol) rescue puffs as needed
Drug: Beclomethasone dipropionate
Beclomethasone diproprionate HFA (QVAR® 40 mcg Inhalation Aerosol) rescue puffs as needed
Drug: Albuterol sulfate
Albuterol sulfate HFA (ProAir® 90 mcg Inhalation Aerosol) rescue puffs as needed
D: Placebo Comparator
Albuterol sulfate HFA (ProAir® 90 mcg Inhalation Aerosol) rescue puffs as needed
Drug: Albuterol sulfate
Albuterol sulfate HFA (ProAir® 90 mcg Inhalation Aerosol) rescue puffs as needed

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. Asthma is commonly treated with two types of medications: long-term control medication, such as inhaled corticosteroids (ICS), which is taken on a regular schedule to prevent symptoms and keep asthma under control, and quick-relief, or "rescue" medication, such as albuterol, which is used on an as-needed-basis with the onset of symptoms or an asthma attack. The purpose of this study is to assess the impact and severity of asthma exacerbations that occur in children with mild persistent asthma who are receiving ICS on a daily basis plus ICS and albuterol as rescue medications.

This study will begin with a 4-week screening period during which participants will be monitored while they use an inhaler with a low dose of ICS medication. Study visits will occur at study entry and Week 4. Participants will undergo a physical examination, lung function and airway pressure testing, and blood collection. At the Week 4 study visit, participants will be randomly assigned to one of the following four groups for 44 weeks of treatment:

  • Group 1 will take ICS twice a day and ICS plus albuterol as rescue medication
  • Group 2 will take ICS twice a day and placebo ICS plus albuterol as rescue medication
  • Group 3 will take placebo ICS twice a day and ICS plus albuterol as rescue medication
  • Group 4 will take placebo ICS twice a day and placebo ICS plus albuterol as rescue medication

Each participant will receive three inhalers with their assigned medication. One inhaler will be used twice daily throughout the study. The other two inhalers will be used consecutively on an as-needed-basis as rescue medication. Study visits will occur at Weeks 8, 16, 24, 32, 40, and 48. A physical examination, blood collection, and lung function and airway pressure testing will occur at selected visits. Questionnaires to assess quality of life and asthma control will also be completed. A methacholine challenge test will be completed at some study visits. This test artificially triggers an asthma attack to determine the severity of an individual's asthma. Throughout the study, participants will record asthma symptoms and rescue medication usage in a daily diary.

  Eligibility

Ages Eligible for Study:   6 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 ICS dose less than or equal to 160 mcg per day of a beclomethasone-equivalent or a 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+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)
  • 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 PC20 methacholine FEV1 is less than or equal to 12.5 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 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

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00394329

Locations
United States, Arizona
University of Arizona College of Medicine Recruiting
Tucson, Arizona, United States, 85724
Contact: Fernando D. Martinez, MD     520-626-6387     fernando@resp-sci.arizona.edu    
Contact: Wayne Morgan, MD     520-626-7780     wmorgan@resp-sci.arizona.edu    
Principal Investigator: Fernando D. Martinez, MD            
United States, California
Kaiser Permanente Medical Center Recruiting
San Diego, California, United States, 92111
Contact: Robert S. Zeiger, MD, PhD     858-573-5408     robert.s.zeiger@kp.org    
Contact: Gregory P. Heldt, MD     619-543-3790     gheldt@ucsd.edu    
Principal Investigator: Robert S. Zeiger, MD, PhD            
Los Angeles, Kaiser Permanente Allergy Department Recruiting
Los Angeles, California, United States, 90027
Contact: Michael S. Kaplan, MD     323-783-4642     michael.s.kaplan@kp.org    
Sub-Investigator: Michael S. Kaplan, MD            
United States, Colorado
National Jewish Medical and Research Center Recruiting
Denver, Colorado, United States, 80206
Contact: Stanley J. Szefler, MD, PhD     303-398-1193     szeflers@njc.org    
Contact: Gary Larsen, MD     303-398-1617     larseng@njc.org    
Principal Investigator: Stanley J. Szefler, MD, PhD            
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Robert C. Strunk, MD     341-454-2284     strunk@kids.wustl.edu    
Contact: Leonard Bacharier, MD     314-454-4233     bacharier_l@kids.wustl.edu    
Principal Investigator: Robert C. Strunk, MD            
United States, Wisconsin
University of Wisconsin - Madison Recruiting
Madison, Wisconsin, United States, 53792-3244
Contact: Robert F. Lemanske, Jr., MD     608-265-2206     rfl@medicine.wisc.edu    
Contact: Christine A. Sorkness, PharmD     608-263-2866     sorkness@facstaff.wisc.edu    
Principal Investigator: Robert F. Lemanske, Jr., MD            
Sponsors and Collaborators
Investigators
Principal Investigator: David T. Mauger, PhD Penn State College of Medicine
Principal Investigator: Stanley J. Szefler, MD, PhD National Jewish Health
Principal Investigator: Robert F. Lemanske, Jr., MD University of Wisconsin, Madison
Principal Investigator: Robert S. Zeiger, MD, PhD Kaiser Permanente Medical Center
Principal Investigator: Robert C. Strunk, MD Washington University School of Medicine
Principal Investigator: Fernando D. Martinez, MD University of Arizona College of Medicine
Study Chair: Lynn M. Taussig, MD University of Denver
  More Information

Additional Information:
No publications provided

Responsible Party: Pennsylvania State University, College of Medicine ( Vernon M. Chinchilli, PhD )
Study ID Numbers: 445, 5U10HL064313, 5U10HL064288, 5U10HL064305, 5U10HL064295, 5U10HL064287, 5U10HL064307
Study First Received: October 30, 2006
Last Updated: February 11, 2009
ClinicalTrials.gov Identifier: NCT00394329     History of Changes
Health Authority: United States: Food and Drug Administration

Study placed in the following topic categories:
Anti-Inflammatory Agents
Procaterol
Neurotransmitter Agents
Adrenergic beta-Agonists
Adrenergic Agents
Bronchial Diseases
Hormone Antagonists
Albuterol
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Asthmatic Agents
Asthma
Beclomethasone
Hormones
Glucocorticoids
Adrenergic Agonists
Lung Diseases, Obstructive
Hypersensitivity
Respiratory Tract Diseases
Lung Diseases
Hypersensitivity, Immediate
Peripheral Nervous System Agents
Bronchodilator Agents
Respiratory Hypersensitivity

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Respiratory System Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Bronchial Diseases
Adrenergic Agents
Albuterol
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Beclomethasone
Reproductive Control Agents
Hormones
Adrenergic Agonists
Hypersensitivity
Lung Diseases, Obstructive
Respiratory Tract Diseases
Tocolytic Agents
Therapeutic Uses
Immune System Diseases
Adrenergic beta-Agonists
Asthma
Anti-Asthmatic Agents
Glucocorticoids
Pharmacologic Actions
Autonomic Agents
Lung Diseases
Hypersensitivity, Immediate
Peripheral Nervous System Agents
Bronchodilator Agents
Respiratory Hypersensitivity

ClinicalTrials.gov processed this record on May 07, 2009