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AsthmaPhase 3BADGERNCT00395304

Childhood Asthma Research and Education (CARE) Network Trial - Best Add-On Therapy Giving Effective Response (BADGER)

A Phase 3 study testing fluticasone propionate + montelukast, fluticasone propionate and fluticasone propionate + salmeterol in people with Asthma, run by Milton S. Hershey Medical Center at 5 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. While a low dose of inhaled corticosteroids (ICS) may effectively control symptoms, some children may require additional medications to maintain adequate asthma control. Read more about this study

Who is it for?
Ages 6 to 18 years
Conditions the study is for
Asthma
What is being tested?
fluticasone propionate + montelukast, fluticasone propionate and fluticasone propionate + salmeterol
Could I receive a placebo?
No, everyone receives an active treatment
How many people
182 participants
Where
5 sitesUnited States
Study dates
Mar 2007to 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 (e.g., cough, wheezing, shortness of breath) and meets at least one of the following criteria:
  • Naïve to controller therapy and meeting National Asthma Education and Prevention Program (NAEPP) criteria for mild-moderate persistent asthma (symptoms at least 2 days per week and/or night-time awakenings due to asthma at least 2 nights per month)
  • Current uncontrolled asthma (meets NAEPP criteria for mild-moderate persistent asthma) while receiving an ICS dose greater than or equal to 200 ug per day of fluticasone equivalent or some form of non-ICS controller therapy (e.g., montelukast, theophylline, cromolyn)
  • Asthma is currently under control while receiving an ICS dose between 300 to 400 ug per day of fluticasone equivalent and willing to consider changing current treatment to monotherapy with one dose of ICS (current standard of care)
  • Asthma is currently under control while receiving some form of combination therapy, such as ICS less than or equal to 200 ug per day of fluticasone equivalent in addition to a non-ICS controller therapy (e.g., LABA, montelukast, theophylline, cromolyn), and willing to consider changing current treatment to monotherapy with one dose of ICS (current standard of care)
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  • FEV1 reversibility of at least 12% following bronchodilator administration (4 puffs) at study visit 1. Individuals will need to hold albuterol, montelukast, theophylline, ipratropium bromide (or other anticholinergics) and LABAs per study instructions prior to reversibility testing. If an individual is receiving these types of medications prior to study visit 1, he/she may be brought back to the clinical center within 1 week following appropriate medication withholding to attempt qualification by reversibility criteria. If the individual does not meet this requirement, they may qualify for enrollment if their PC20 methacholine FEV1 is less than or equal to 12.5 mg/ml at the time of randomization. If FEV1 is less than 70%, thus precluding the methacholine challenge at this visit, then completion of the visit will be postponed several days and an additional attempt to obtain a methacholine challenge test will be made. If the methacholine challenge still cannot be performed, an individual may still qualify by reversibility criteria at this visit.
  • 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
  • Prior to being randomly assigned to a treatment group, participants must meet the following criteria to remain in the study:
  • Lack of acceptable asthma control during the 8-week screening period as defined by the following criteria:
  • 1) On average, on more than 2 days per week, one or all 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 post bronchodilator PEF value obtained at study visit 1) OR
  • On average, more than 1 night-time awakening due to asthma, during each 2-week period

Who cannot join

  • Corticosteroid treatment for any condition prior to study entry within the following defined timepoints:
  • Oral - Use within 2 weeks of the screening visit
  • Injectable - Use within 2 weeks of the screening visit
  • Nasal - 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
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  • More than three hospitalizations 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 or would place the participant at increased risk while participating in the study
  • History of cataracts, glaucoma, or any other medical disorder associated with an adverse effect to corticosteroids
  • Gastroesophageal reflux symptoms not controlled by standard medical therapy
  • History of significant asthma exacerbation within 2 weeks of study visit 1 or more than 5 courses of systemic corticosteroids in the year prior to study entry
  • History of a life-threatening asthma exacerbation requiring intubation, mechanical ventilation, or resulting in a hypoxic seizure within the 5 years prior to study entry
  • History of adverse reactions to ICS, LTRA, or LABA preparations or any of their ingredients
  • Receiving hyposensitization therapy other than an established maintenance regimen (i.e., continuous regimen for at least 3 months prior to study entry)
  • Pregnant or breastfeeding
  • Inability to perform study procedures
  • Refusal to consent to a genotype evaluation
  • Inability of the child to ingest the study drug
  • Cigarette smoking or smokeless tobacco use in the year prior to study entry
  • Current participation or participation in the month prior to 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

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • National Jewish Medical and Research Center

    Denver, Colorado, 80206

  • University of Wisconsin - Madison

    Madison, Wisconsin, 53792

  • 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

Asthma is a common, serious illness among children in the United States. While a low dose of inhaled corticosteroids (ICS) may effectively control symptoms, some children may require additional medications to maintain adequate asthma control. This study compares the effectiveness of a higher dose of ICS, ICS combined with a long-acting beta-agonist (LABA) medication, and ICS combined with a leukotriene receptor antagonist (LTRA) medication at reducing the impact and severity of asthma exacerbations that occur in children with mild to moderate persistent asthma.

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. Low doses of ICS are commonly prescribed to prevent symptoms and keep asthma under control. While this is usually sufficient to prevent asthma attacks, some children do not respond well to low dose ICS alone. For these children, their asthma symptoms may be more effectively controlled by either receiving a higher dose of ICS or receiving LABA or LTRA medications in combination with a low dose of ICS. Both LABA and LTRA medications are used to help control moderate to severe asthma. The purpose of this study is to compare the effectiveness of a high dose of ICS versus a low dose of ICS plus either LABA or LTRA medication at improving asthma control and reducing the severity of symptoms that occur in children with mild to moderate persistent asthma.

This study began with an 8-week screening period during which participants were monitored while they used an inhaler with a low dose of ICS medication. During this time, participants also attended one or two study visits. At each visit, participants underwent a physical examination, exhaled nitric oxide analysis, and lung function and airway pressure testing. After enrollment criteria were met, participants underwent these same evaluations again, and they completed questionnaires to assess asthma control, quality of life, and home environmental factors. Blood was collected and a methacholine challenge test was completed, which artificially triggers an asthma attack to determine the severity of an individual's asthma. Participants then were randomly assigned to one of six treatment sequences, each of which includes the following three regimens in a different order:

  • Low dose of ICS and salmeterol, a LABA medication
  • Low dose of ICS and montelukast, a LTRA medication
  • Double dose of ICS

Each treatment period lasted 16 weeks, with study visits occurring weekly. A physical examination, blood collection, lung function and airway pressure testing, a methacholine challenge test, and questionnaires occurred at selected visits. Throughout the study, participants recorded asthma symptoms, peak expiratory flow rates, and rescue medication usage in a daily diary. The entire length of the study did not exceed 56 weeks.

Conditions
Asthma
Being tested
fluticasone propionate + montelukast, fluticasone propionate, fluticasone propionate + salmeterol
Medical subject headings
Asthma

What participants receive

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

  • fluticasone propionate + montelukastDrug

    Also called Flovent Diskus® + Singulair®

    Dry-powder inhaler fluticasone 100 mcg bid (Flovent Diskus®, GlaxoSmithKline) plus Montelukast 5 or 10 mg qd (Singulair®, Merck)

  • fluticasone propionateDrug

    Also called Flovent Diskus®

    Dry-powder inhaler fluticasone 250 mcg bid (Flovent Diskus®, GlaxoSmithKline)

  • fluticasone propionate + salmeterolDrug

    Also called Advair Diskus®

    Dry-powder inhaler fluticasone + salmeterol combination 100 mcg/50 mcg bid (Advair Diskus®, GlaxoSmithKline)

Study groups in NCT00395304
Study groupRoleWhat they receive
Sequence #1Experimentalfluticasone propionate + montelukast, followed by fluticasone propionate, followed by fluticasone propionate + salmeterol
Receives: Drug: fluticasone propionate + montelukast; Drug: fluticasone propionate; Drug: fluticasone propionate + salmeterol
Sequence #2Experimentalfluticasone propionate + montelukast, followed by fluticasone propionate + salmeterol, followed by followed by fluticasone propionate
Receives: Drug: fluticasone propionate + montelukast; Drug: fluticasone propionate; Drug: fluticasone propionate + salmeterol
Sequence #3Experimentalfluticasone propionate + salmeterol, followed by fluticasone propionate, followed by fluticasone propionate + montelukast
Receives: Drug: fluticasone propionate + montelukast; Drug: fluticasone propionate; Drug: fluticasone propionate + salmeterol
Sequence #4Experimentalfluticasone propionate + salmeterol, followed by fluticasone propionate + montelukast, followed by fluticasone propionate
Receives: Drug: fluticasone propionate + montelukast; Drug: fluticasone propionate; Drug: fluticasone propionate + salmeterol
Sequence #5Experimentalfluticasone propionate, followed by fluticasone propionate + salmeterol, followed by fluticasone propionate + montelukast
Receives: Drug: fluticasone propionate + montelukast; Drug: fluticasone propionate; Drug: fluticasone propionate + salmeterol
Sequence #6Experimentalfluticasone propionate, followed by fluticasone propionate + montelukast, followed by fluticasone propionate + salmeterol
Receives: Drug: fluticasone propionate + montelukast; Drug: fluticasone propionate; Drug: fluticasone propionate + salmeterol

What is being measured

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

  1. The Number of Participants With a Differential Response to the Three Step-up Therapies Based on Fixed Threshold Criteria for the Following Three Asthma Control Measures: Use of Oral Prednisone for Acute Asthma Exacerbations, Asthma Control Days and FEV1.

    One treatment period was ranked as better than another if the total amount of prednisone received during the period was at least 180 mg less, if the number of annualized asthma-control days during the final 12 weeks of the period was increased by at least 31 days, or if the FEV1 at the end of the period was at least 5% higher. If the prednisone threshold was met, then we ignored the number of asthmacontrol days and the FEV1. If the threshold for asthma-control days was met, then we ignored the FEV1. Otherwise, the order of response was determined by the FEV1.

    Measured: Measured during the last 12 weeks of each 16-week treatment period

Secondary outcomes (13)

  1. Change From Baseline in the Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) % Predicted

    Measured: Measured during the last 12 weeks of each 16-week treatment period

  2. Change From Baseline in the Post-bronchodilator FEV1 Percent Predicted

    Measured: Measured during the last 12 weeks of each 16-week treatment period

  3. Change From Baseline in the Pre-bronchodilator Forced Vital Capacity (FVC) % Predicted

    Measured: Measured during the last 12 weeks of each 16-week treatment period

  4. Change From Baseline in the Pre-bronchodilator FEV1/FVC Ratio

    Measured: Measured during the last 12 weeks of each 16-week treatment period

  5. Change From Baseline in the Morning Peak Expiratory Flow Rate (PEFR) % Predicted

    Measured: Measured during the last 12 weeks of each 16-week treatment period

  6. Change From Baseline in the Evening Peak Expiratory Flow Rate (PEFR) % Predicted

    Measured: Measured during the last 12 weeks of each 16-week treatment period

  7. Change From Baseline in the Peak Expiratory Flow Rate (PEFR) Variability

    PEFR variability is calculated as 100% times the difference between the evening and morning PEFR values, divided by the average of the evening and morning PEFR values, i.e., PEFR variability = 100% x (morning PEFR - evening PEFR)/((morning PEFR + evening PEFR)/2)

    Measured: Measured during the last 12 weeks of each 16-week treatment period

  8. Change From Baseline in the Impulse Oscillometry Resistance at 5 Hertz

    Change from baseline in the impulse oscillometry resistance at 5 Hertz, measured in kiloPascals per liters per second

    Measured: Measured during the last 12 weeks of each 16-week treatment period

  9. Change From Baseline in the Logarithm Base 2 of the Methacholine PC20

    The methacholine PC20 is the concentration of methacholine that causes a 20% decrease in the pre-bronchodilator FEV1. The logarithm base 2 transformation converts the PC20 into doubling dilutions.

    Measured: Measured during the last 12 weeks of each 16-week treatment period

  10. Change From Baseline in the Natural Logarithm of Exhaled Nitric Oxide (eNO)

    Measured: Measured during the last 12 weeks of each 16-week treatment period

  11. Change From Baseline in the Asthma Control Test (ACT)

    The ACT consists of five items, each scored as 1 (worst) to 5 (best). The five items are averaged.

    Measured: Measured during the last 12 weeks of each 16-week treatment period

  12. Change From Baseline in Asthma Quality of Life

    Asthma quality of life is measured as the average of 23 questions, each of which is scored from 1 (worse) to 7 (best)

    Measured: Measured during the last 12 weeks of each 16-week treatment period

  13. Number of Participants With Asthma Exacerbations

    An asthma exacerbation was defined as the administration of a course of oral/systemic prednisone for the treatment of asthma.

    Measured: Measured during the last 12 weeks of each 16-week treatment period

Timeline

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

  1. First posted2 Nov 2006 (estimated)
  2. Study startMar 2007
  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
Crossover
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
182 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00395304
Sponsor's protocol ID
444
Other IDs
5U10HL064313, 5U10HL064288, 5U10HL064305, 5U10HL064295, 5U10HL064287, 5U10HL064307
Acronym
BADGER
Status last verified
May 2018
First submitted
31 Oct 2006
Last updated
2 Jul 2018
Data monitoring committee
Yes

Publications

  • Lemanske RF Jr, Mauger DT, Sorkness CA, Jackson DJ, Boehmer SJ, Martinez FD, Strunk RC, Szefler SJ, Zeiger RS, Bacharier LB, Covar RA, Guilbert TW, Larsen G, Morgan WJ, Moss MH, Spahn JD, Taussig LM; Childhood Asthma Research and Education (CARE) Network of the National Heart, Lung, and Blood Institute. Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. N Engl J Med. 2010 Mar 18;362(11):975-85. doi: 10.1056/NEJMoa1001278. Epub 2010 Mar 2.

    PubMed 20197425

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing fluticasone propionate + montelukast, fluticasone propionate and fluticasone propionate + salmeterol in people with Asthma, run by Milton S. Hershey Medical Center at 5 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 17 inclusion and 22 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 5 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. 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 Sep 2010). 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?

The Number of Participants With a Differential Response to the Three Step-up Therapies Based on Fixed Threshold Criteria for the Following Three Asthma Control Measures: Use of Oral Prednisone for Acute Asthma Exacerbations, Asthma Control Days and FEV1. (time frame: Measured during the last 12 weeks of each 16-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 NCT00395304, which also lists 1 linked publication.

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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