Official Title: “Asthma Clinical Research Network (ACRN) Trial - Best Adjustment Strategy for Asthma in Long Term (BASALT)”

Asthma can be effectively controlled using inhaled corticosteroid medication. Treatment with inhaled corticosteroids often requires periodic adjustments to medication dosing and frequency levels. This study examines whether it is more beneficial to adjust corticosteroid treatment based on asthma symptoms and/or biomarkers of lung function versus standard medical guidelines.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: June 2010

Asthma is a common, long-term disease that is caused by inflammation of the airways. Symptoms of asthma may include wheezing, coughing, shortness of breath, and chest tightness. The most common treatment for asthma is the use of inhaled corticosteroid medications with periodic adjustments to treatment intensity. For example, corticosteroid dosage is increased when asthma symptoms worsen and decreased when symptoms improve. However, guidelines for making these adjustments, especially reduced intensity adjustments, have not been well established.

In people who are initially well controlled on daily low-dose inhaled corticosteroid therapy, symptom-based adjustment (SBA) and/or biomarker-based adjustment (BBA) of inhaled corticosteroid therapy may be more beneficial at maintaining asthma control than standard, guideline-based adjustments (GBA). The purpose of this study is to determine if adjusting treatment based on symptoms and/or lung function biomarkers is more effective at controlling asthma than adjusting corticosteroid use based on standardized medical guidelines.

This study begins with a 4-week period during which participants are monitored while they use an inhaler containing a low dose of inhaled corticosteroid medication. Participants then are assigned to take part in either the BASALT study or the Tiotropium as an Alternative to Long-Acting Beta-Agonists and Corticosteroids (TALC) study, which is a separate Asthma Clinical Research Network (ACRN) study. Participants in BASALT undergo 2 to 4 weeks of adherence testing, which involves using three inhalers that have electronic monitoring devices attached to them. Participants also are asked to measure and record their breathing rates and lung function in a study diary.

BASALT participants are then randomly assigned to one of three treatment groups: SBA, BBA, or GBA. Each participant is given four inhalers: one inhaler contains albuterol, which is used on an as-needed basis as rescue medication; one inhaler contains corticosteroid medication; and two inhalers contain placebo. One of the latter three inhalers is used each time the albuterol inhaler is used, and the other two inhalers are used on a daily basis. Study visits occur at Weeks 2, 4, 6, 12, 18, 24, 30, and 36 of the treatment period. Inhalers are adjusted during these visits based on SBA, BBA, or GBA guidelines. At selected visits, the following procedures occur: physical exam; blood collection; allergy skin testing; heart rate monitoring; lung function and airway testing; methacholine challenge test to determine asthma severity; and questionnaires to assess asthma control, quality of life, and other healthcare factors. Participants record asthma symptoms, peak flow measurements, and medication usage in a daily diary.

Intervention(s) in this Clinical Trial

• Drug: Beclomethasone dipropionate
  • Beclomethasone dipropionate HFA (QVAR® 40 mcg or QVAR® 80 mcg)

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Symptom-based adjustment of beclomethasone dipropionate HFA (QVAR® 40 mcg or QVAR® 80 mcg)
• Experimental: 2
  • Biomarker-based adjustment of beclomethasone dipropionate HFA (QVAR® 40 mcg or QVAR® 80 mcg)
• Experimental: 3
  • Guideline-based adjustment of beclomethasone dipropionate HFA (QVAR® 40 mcg or QVAR® 80 mcg)

Primary Measures

• Time to treatment failure
  • Time Frame: Measured during the 36-week treatment period
    Safety Issue?: No

Secondary Measures

• Number of episodes of treatment failure
  • Time Frame: Measured during the 36-week treatment period
    Safety Issue?: No
• Time to first asthma exacerbation
  • Time Frame: Measured during the 36-week treatment period
    Safety Issue?: No
• Number of asthma exacerbations
  • Time Frame: Measured during the 36-week treatment period
    Safety Issue?: No
• Tests of airway caliber and responsiveness (FEV1 pre- and post-bronchodilator inhalation), methacholine PC20
  • Time Frame: Measured during the 36-week treatment period
    Safety Issue?: No
• Tests of airway inflammation (exhaled breath condensate [EBC], fractional exhaled nitric oxide [FeNO], sputum eosinophils)
  • Time Frame: Measured during the 36-week treatment period
    Safety Issue?: No
• Quality-of-life (AQLQ), asthma control questionnaire (ACQ), and number of visit days that ACQ is less than 1.25
  • Time Frame: Measured during the 36-week treatment period
    Safety Issue?: No
• Total amount of oral prednisone required and total amount of inhaled steroids
  • Time Frame: Measured during the 36-week treatment period
    Safety Issue?: No
• Adverse events
  • Time Frame: Measured during the 36-week treatment period
    Safety Issue?: Yes

Inclusion Criteria for BASALT and TALC Studies:

• Clinical history consistent with asthma
• FEV1 greater than 40% of predicted value
• Asthma confirmed by one of the following two criteria:
• 1. Beta-agonist reversibility to 4 puffs albuterol of at least 12% OR
• 2. PC20 FEV1 methacholine of 8 mg/mL or less when not on an inhaled corticosteroid, or 16 mg/mL or less when on an inhaled corticosteroid
• Need for daily controller therapy (i.e., inhaled corticosteroids, leukotriene modifiers, and/or long-acting beta-agonists) based on one or more of the following criteria:
• 1. Received prescription for or used asthma controller within the 12 months prior to study entry OR
• 2. Experienced symptoms for more than twice a week and not on asthma controller
• If on inhaled steroids (any drug at any dose not exceeding the equivalent of 1000 mcg of fluticasone daily), participant must have been on a stable dose for at least 2 weeks prior to study entry
• Non-smoker (i.e., total lifetime smoking history less than 10 pack-years; no smoking for at least 1 year prior to study entry)
• Willing to use an effective form of birth control throughout the study

Inclusion Criteria for BASALT Study:

• Ability to measure peak expiratory flow (PEF) each morning using the electronic peak flow meter (EPFM) device and to accurately transcribe the PEF measurements onto the diary cards at least 75% of the time during the last 2 weeks of the adherence testing period
• 75% compliance with recording peak flow measurements and symptoms in a symptom diary during the last 2 weeks of the adherence testing period
• Ability to take Inhalers A, B, and C at least 75% of scheduled doses; 75% compliance per inhaler is required
• No treatment failure (includes significant asthma exacerbation) within the last 4 weeks

Exclusion Criteria for BASALT and TALC Studies:

• Lung disease other than asthma, including chronic obstructive pulmonary disease (COPD) and chronic bronchitis
• Established or suspected diagnosis of vocal cord dysfunction
• Significant medical illness other than asthma
• History of respiratory tract infection within the 4 weeks prior to study entry
• History of a significant exacerbation of asthma within the 4 weeks prior to study entry
• History of life-threatening asthma requiring treatment with intubation and mechanical ventilation in the 5 years prior to study entry
• Hyposensitization therapy other than an established maintenance regimen
• Inability to coordinate use of the delivery devices used in the study, based on the opinion of the investigator or clinical coordinator
• Pregnant

Exclusion Criteria for BASALT Study:

• Inability to coordinate use of the medication delivery devices used in the study, based on the opinion of the investigator or clinical coordinator

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Overall Clinical Trial Officials and Contacts

William J. Calhoun, MD Principal Investigator University of Texas, Galveston  

Overall Contact: Vernon M. Chinchilli, PhD 717-531-4262 vchinchi@psu.edu

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00495157

Study ID Number: 494

ClinicalTrials.gov Identifier: NCT00495157

Health Authority: United States: Federal Government

Click here for the Asthma Clinical Research Network Web site