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

NCT00394329 | Completed Phase 3 Results DMC

• 7 other identifiers: 4455U10HL0643135U10HL0642885U10HL0643055U10HL0642955U10HL0642875U10HL064307
• Study Type: interventional
• Target: 288
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• Participants Experiencing an Asthma Exacerbation That Requires Systemic Corticosteroid Therapy

  Measured during the 44-week treatment period

Secondary Outcomes (9)

• Change Between Week 44 and Week 0 in the Asthma Control Days

  An asthma control day was determined daily during each of the 44-week treatment periods. The primary analysis constructed the change between week 14 and week 0.

• Change Between Week 44 and Week 0 in Rescue Albuterol Puffs Per Day

  Rescue albuterol puffs were measured daily during the 44-week treatment period. The primary analysis constructed the change between week 44 and week 0.

• Change Between Week 44 and Week 0 in the Pre-bronchodilator Forced Expiratory Volume in One Second (FEV!)

  Pre-bronchodilator FEV1 was measured on seven occasions during the 44-week treatment period. The primary analysis constructed the change between week 44 and week 0.

• Change Between Week 44 and Week 0 in the Morning Peak Expiratory Flow Rate (PEFR)

  Morning PEFR was measured daily during the 44-week treatment period. The primary analysis constructed the change between week 44 and week 0.

• Change Between Week 44 and Week 0 in the Evening Peak Expiratory Flow Rate Variability (PEFR)

  Evening PEFR was measured daily during the 44-week treatment period. The primary analysis constructed the change between week 44 and week 0.

Study Arms (4)

Daily ICS + Rescue ICS

EXPERIMENTAL

Beclomethasone dipropionate administered via a hydrofluoroalkane (HFA) inhaler (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

Drug: Beclomethasone dipropionate; Drug: Albuterol sulfate

Daily ICS

ACTIVE COMPARATOR

Beclomethasone dipropionate administered via a hydrofluoroalkane (HFA) inhaler (QVAR® 40 mcg Inhalation Aerosol) one puff bid + albuterol sulfate HFA (ProAir® 90 mcg Inhalation Aerosol) rescue puffs as needed

Drug: Beclomethasone dipropionate; Drug: Albuterol sulfate

Rescue ICS

EXPERIMENTAL

Beclomethasone dipropionate administered via a hydrofluoroalkane (HFA) inhaler (QVAR® 40 mcg Inhalation Aerosol) rescue puffs as needed + albuterol sulfate HFA (ProAir® 90 mcg Inhalation Aerosol) rescue puffs as needed

Drug: Beclomethasone dipropionate; Drug: Albuterol sulfate

Placebo

PLACEBO COMPARATOR

Albuterol sulfate administered via a hydrofluoroalkane (HFA) inhaler (ProAir® 90 mcg Inhalation Aerosol) rescue puffs as needed

Drug: Albuterol sulfate

Interventions

Beclomethasone dipropionate DRUG

Beclomethasone dipropionate HFA (QVAR® 40 mcg Inhalation Aerosol) one puff bid

Also known as: QVAR®

Daily ICS; Daily ICS + Rescue ICS

Albuterol sulfate DRUG

Albuterol sulfate HFA (ProAir® 90 mcg Inhalation Aerosol) rescue puffs as needed

Also known as: ProAir®

Daily ICS; Daily ICS + Rescue ICS; Placebo; Rescue ICS

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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:
• 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
• 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:
• On average, on more than 2 days per week, experiences one or more of the following:
• Diary-reported symptoms
• The use of inhaled bronchodilator (not including pre-exercise)
• 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
• More than 1 night-time awakening due to asthma

You may not qualify if:

• Corticosteroid treatment for any condition prior to study entry within the following defined timepoints:
• Oral - Use within 2-week period of the screening visit
• Injectable - Use within 2-week period of the screening visit
• 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

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (6)

University of Arizona College of Medicine

Tucson, Arizona, 85724, United States

Location

Los Angeles, Kaiser Permanente Allergy Department

Los Angeles, California, 90027, United States

Location

Kaiser Permanente Medical Center

San Diego, California, 92111, United States

Location

National Jewish Medical and Research Center

Denver, Colorado, 80206, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Wisconsin - Madison

Madison, Wisconsin, 53792-3244, United States

Location

Related Publications (2)

• Martinez FD, Chinchilli VM, Morgan WJ, Boehmer SJ, Lemanske RF Jr, Mauger DT, Strunk RC, Szefler SJ, Zeiger RS, Bacharier LB, Bade E, Covar RA, Friedman NJ, Guilbert TW, Heidarian-Raissy H, Kelly HW, Malka-Rais J, Mellon MH, Sorkness CA, Taussig L. Use of beclomethasone dipropionate as rescue treatment for children with mild persistent asthma (TREXA): a randomised, double-blind, placebo-controlled trial. Lancet. 2011 Feb 19;377(9766):650-7. doi: 10.1016/S0140-6736(10)62145-9. Epub 2011 Feb 14.

  PMID: 21324520 RESULT

• Kew KM, Flemyng E, Quon BS, Leung C. Increased versus stable doses of inhaled corticosteroids for exacerbations of chronic asthma in adults and children. Cochrane Database Syst Rev. 2022 Sep 26;9(9):CD007524. doi: 10.1002/14651858.CD007524.pub5.

  PMID: 36161875 DERIVED

Related Links

• Click here for the Childhood Asthma Research and Education (CARE) Network web site

MeSH Terms

Conditions

Asthma

Interventions

Beclomethasone; Albuterol; Procaterol

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Chlorinated; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Hydroxyquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Vernon M. Chinchilli, PhD
• Organization: Penn State College of Medicine

vchinchi@psu.edu

717-531-4262

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

• Lynn M. Taussig, MD

  University of Denver

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chair, Department of Public Health Sciences

Study Record Dates

• First Submitted: October 30, 2006
• First Posted: November 1, 2006
• Study Start: November 1, 2006
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: July 2, 2018
• Results First Posted: May 17, 2013

Record last verified: 2018-05

Locations

US (6)