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AsthmaPhase 3TREXANCT00394329

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

A Phase 3 study testing Beclomethasone dipropionate and Albuterol sulfate in people with Asthma, run by Milton S. Hershey Medical Center at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 6 to 18 years
Conditions the study is for
Asthma
What is being tested?
Beclomethasone dipropionate and Albuterol sulfate
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
288 participants
Where
6 sitesUnited States
Study dates
Nov 2006to Dec 2011
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
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  • 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
  • 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.

Who cannot join

  • 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
Show all 19Show fewer
  • 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

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • National Jewish Medical and Research Center

    Denver, Colorado, 80206

  • Los Angeles, Kaiser Permanente Allergy Department

    Los Angeles, California, 90027

  • University of Wisconsin - Madison

    Madison, Wisconsin, 53792-3244

  • Kaiser Permanente Medical Center

    San Diego, California, 92111

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • University of Arizona College of Medicine

    Tucson, Arizona, 85724

Other trials in United States

About this study

Official title: Childhood Asthma Research and Education (CARE) Network Trial - Treating Children to Prevent Exacerbations of Asthma (TREXA)

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.

Read the 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.

Conditions
Asthma
Being tested
Beclomethasone dipropionate, Albuterol sulfate
Medical subject headings
Asthma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Beclomethasone dipropionateDrug

    Also called QVAR®

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

  • Beclomethasone dipropionateDrug

    Also called QVAR®

    Beclomethasone dipropionate HFA (QVAR® 40 mcg Inhalation Aerosol) rescue puffs as needed

  • Albuterol sulfateDrug

    Also called ProAir®

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

Study groups in NCT00394329
Study groupRoleWhat they receive
Daily ICS + Rescue ICSExperimentalBeclomethasone 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
Receives: Drug: Beclomethasone dipropionate; Drug: Albuterol sulfate
Daily ICSActive comparatorBeclomethasone 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
Receives: Drug: Beclomethasone dipropionate; Drug: Albuterol sulfate
Rescue ICSExperimentalBeclomethasone 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
Receives: Drug: Beclomethasone dipropionate; Drug: Albuterol sulfate
PlaceboPlacebo comparatorAlbuterol sulfate administered via a hydrofluoroalkane (HFA) inhaler (ProAir® 90 mcg Inhalation Aerosol) rescue puffs as needed
Receives: Drug: Albuterol sulfate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Participants Experiencing an Asthma Exacerbation That Requires Systemic Corticosteroid Therapy

    Measured: Measured during the 44-week treatment period

Secondary outcomes (9)

  1. Change Between Week 44 and Week 0 in the Asthma Control Days

    Measured: 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.

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

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

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

    Measured: 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.

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

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

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

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

  6. Change Between Week 44 and Week 0 Peak Expiratory Flow Rate (PEFR) Variability

    PEFR variability represents the relative change between the evening and morning PEFR measurements, so it could be a positive or negative number. It was measured daily during the 44-week treatment period. Specifically, the PEFR variability on a specific day is defined as 100% x (evening PEFR - morning PEFR)/{0.5*(evening PEFR + morning PEFR)}

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

  7. Change Between Week 44 and Week 0 in the Exhaled Nitric Oxide (eNO) Measured in Parts Per Billion

    Measured: eNO was measured on seven occasions during the 44-week treatment period. The primary analysis constructed the change between week 44 and week 0.

  8. Change Between Week 44 and Week 0 in the Asthma-specific Quality of Life Assessment

    The asthma-specific quality of life scale ranged from 1 (worst) to 7 (best)

    Measured: The asthma-specific quality of life assessment was measured on seven occasions during the 44-week treatment period. The primary analysis constructed the change between week 44 and week 0.

  9. Change Between Week 44 and Week 0 in the Asthma Control Test (ACT)

    The ACT consisted of five questions, each ranging from 1 (worst) to 5 (best). The five questions were summed to yield an overall score that ranged from 5 (worst) to 25 (best).

    Measured: The ACT was measured on seven occasions during the 44-week treatment period. The primary analysis constructed the change between week 44 and week 0.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Nov 2006 (estimated)
  2. Study startNov 2006
  3. Primary completionDec 2011
  4. Study completionDec 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
288 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00394329
Sponsor's protocol ID
445
Other IDs
5U10HL064313, 5U10HL064288, 5U10HL064305, 5U10HL064295, 5U10HL064287, 5U10HL064307
Acronym
TREXA
Status last verified
May 2018
First submitted
30 Oct 2006
Last updated
2 Jul 2018
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 21324520

  • 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.

    PubMed 36161875

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Beclomethasone dipropionate and Albuterol sulfate in people with Asthma, run by Milton S. Hershey Medical Center at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 May 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Participants Experiencing an Asthma Exacerbation That Requires Systemic Corticosteroid Therapy (time frame: Measured during the 44-week treatment period). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00394329, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2018.

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