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

NCT00395304 | Completed Phase 3 Results DMC

• 7 other identifiers: 4445U10HL0643135U10HL0642885U10HL0643055U10HL0642955U10HL0642875U10HL064307
• Study Type: interventional
• Target: 182
• Locations: 1 country
• Sites: 5

Brief 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. 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.

Conditions

Asthma

Outcome Measures

Primary Outcomes (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 during the last 12 weeks of each 16-week treatment period

Secondary Outcomes (13)

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

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

• Change From Baseline in the Post-bronchodilator FEV1 Percent Predicted

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

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

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

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

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

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

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

Study Arms (6)

Sequence #1

EXPERIMENTAL

fluticasone propionate + montelukast, followed by fluticasone propionate, followed by fluticasone propionate + salmeterol

Drug: fluticasone propionate + montelukast; Drug: fluticasone propionate; Drug: fluticasone propionate + salmeterol

Sequence #2

EXPERIMENTAL

fluticasone propionate + montelukast, followed by fluticasone propionate + salmeterol, followed by followed by fluticasone propionate

Drug: fluticasone propionate + montelukast; Drug: fluticasone propionate; Drug: fluticasone propionate + salmeterol

Sequence #3

EXPERIMENTAL

fluticasone propionate + salmeterol, followed by fluticasone propionate, followed by fluticasone propionate + montelukast

Drug: fluticasone propionate + montelukast; Drug: fluticasone propionate; Drug: fluticasone propionate + salmeterol

Sequence #4

EXPERIMENTAL

fluticasone propionate + salmeterol, followed by fluticasone propionate + montelukast, followed by fluticasone propionate

Drug: fluticasone propionate + montelukast; Drug: fluticasone propionate; Drug: fluticasone propionate + salmeterol

Sequence #5

EXPERIMENTAL

fluticasone propionate, followed by fluticasone propionate + salmeterol, followed by fluticasone propionate + montelukast

Drug: fluticasone propionate + montelukast; Drug: fluticasone propionate; Drug: fluticasone propionate + salmeterol

Sequence #6

EXPERIMENTAL

fluticasone propionate, followed by fluticasone propionate + montelukast, followed by fluticasone propionate + salmeterol

Drug: fluticasone propionate + montelukast; Drug: fluticasone propionate; Drug: fluticasone propionate + salmeterol

Interventions

fluticasone propionate + montelukast DRUG

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

Also known as: Flovent Diskus® + Singulair®

Sequence #1; Sequence #2; Sequence #3; Sequence #4; Sequence #5; Sequence #6

fluticasone propionate DRUG

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

Also known as: Flovent Diskus®

Sequence #1; Sequence #2; Sequence #3; Sequence #4; Sequence #5; Sequence #6

fluticasone propionate + salmeterol DRUG

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

Also known as: Advair Diskus®

Sequence #1; Sequence #2; Sequence #3; Sequence #4; Sequence #5; Sequence #6

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 (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)
• 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:
• \) 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)

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

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

Study Sites (5)

University of Arizona College of Medicine

Tucson, Arizona, 85724, 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, United States

Location

Related Publications (1)

• 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.

  PMID: 20197425 RESULT

Related Links

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

MeSH Terms

Conditions

Asthma

Interventions

Fluticasone; montelukast; Fluticasone-Salmeterol Drug Combination

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Salmeterol Xinafoate; Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Drug Combinations; Pharmaceutical Preparations

Limitations and Caveats

The study was not designed or powered to evaluate the long-term safety of long-acting beta-agonists in children. The duration of the trial and its sample size preclude statements regarding long-term risks.

Results Point of Contact

• Title: Vernon M. Chinchilli
• Organization: Penn State Hershey 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: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chair, Department of Public Health Sciences

Study Record Dates

• First Submitted: October 31, 2006
• First Posted: November 2, 2006
• Study Start: March 1, 2007
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: July 2, 2018
• Results First Posted: September 17, 2010

Record last verified: 2018-05

Locations

US (5)