Clinical trial NCT00495157: Asthma Clinical Research Network (ACRN) Trial - Best Adjustment Strategy for Asthma in Long Term (BASALT)
Official title: Asthma Clinical Research Network (ACRN) Trial - Best Adjustment Strategy for Asthma in Long Term (BASALT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2007-07-02
Enrollment: 342
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria for BASALT and TALC Studies:

* Clinical history consistent with asthma
* Forced expiratory volume in one second (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. Methacholine provocative concentration at 20% (PC20) FEV1 of 8 milligrams per millimeter (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 micrograms (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

Primary outcomes:
measure: Time to Treatment Failure (Measured in Days)
timeFrame: Measured during the 36-week treatment period
Secondary outcomes:
measure: Number of Episodes of Treatment Failure
timeFrame: Measured during the 36-week treatment period
measure: Time to First Asthma Exacerbation
timeFrame: Measured during the 36-week treatment period
measure: Number of Asthma Exacerbations
timeFrame: Measured during the 36-week treatment period
measure: Tests of Airway Caliber and Responsiveness (Forced Expiratory Volume in One Second (FEV1) Pre- and Post-bronchodilator Inhalation), Methacholine Provocative Concentration at 20% (PC20)
timeFrame: Measured during the 36-week treatment period
measure: Tests of Airway Inflammation (Exhaled Breath Condensate (EBC), Fractional Exhaled Nitric Oxide (FeNO), Sputum Eosinophils)
timeFrame: Measured during the 36-week treatment period
measure: Quality-of-life (AQLQ), Asthma Control Questionnaire (ACQ), and Number of Visit Days That ACQ is Less Than 1.25
timeFrame: Measured during the 36-week treatment period
measure: Total Amount of Oral Prednisone Required and Total Amount of Inhaled Steroids
timeFrame: Measured during the 36-week treatment period
measure: Adverse Events
timeFrame: Measured during the 36-week treatment period
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Denver
country: United States
facility: National Jewish Medical and Research Center
state: Colorado
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: St. Louis
country: United States
facility: Washington University, St. Louis
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Madison
country: United States
facility: University of Wisconsin, Madison
state: Wisconsin
Study officials:
affiliation: University of Texas, Galveston
name: William J. Calhoun, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Washington University School of Medicine
name: Mario Castro, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Wisconsin, Madison
name: Robert F. Lemanske, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Jewish Health
name: Richard J. Martin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brigham and Women's Hospital
name: Elliot Israel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wake Forest University Health Sciences
name: Stephen P. Peters, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francsico
name: Homer A. Boushey, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Diego
name: Stephen I. Wasserman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University
name: Emily DiMango, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Monica Kraft, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Jewish Health
name: Reuben M. Cherniack, MD
role: STUDY_CHAIR
References:
citation: Lugogo N, Green CL, Agada N, Zhang S, Meghdadpour S, Zhou R, Yang S, Anstrom KJ, Israel E, Martin R, Lemanske RF Jr, Boushey H, Lazarus SC, Wasserman SI, Castro M, Calhoun W, Peters SP, DiMango E, Chinchilli V, Kunselman S, King TS, Icitovic N, Kraft M. Obesity's effect on asthma extends to diagnostic criteria. J Allergy Clin Immunol. 2018 Mar;141(3):1096-1104. doi: 10.1016/j.jaci.2017.04.047. Epub 2017 Jun 15.
citation: Calhoun WJ, Ameredes BT, King TS, Icitovic N, Bleecker ER, Castro M, Cherniack RM, Chinchilli VM, Craig T, Denlinger L, DiMango EA, Engle LL, Fahy JV, Grant JA, Israel E, Jarjour N, Kazani SD, Kraft M, Kunselman SJ, Lazarus SC, Lemanske RF, Lugogo N, Martin RJ, Meyers DA, Moore WC, Pascual R, Peters SP, Ramsdell J, Sorkness CA, Sutherland ER, Szefler SJ, Wasserman SI, Walter MJ, Wechsler ME, Boushey HA; Asthma Clinical Research Network of the National Heart, Lung, and Blood Institute. Comparison of physician-, biomarker-, and symptom-based strategies for adjustment of inhaled corticosteroid therapy in adults with asthma: the BASALT randomized controlled trial. JAMA. 2012 Sep 12;308(10):987-97. doi: 10.1001/2012.jama.10893.
citation: Sutherland ER, Goleva E, Jackson LP, Stevens AD, Leung DY. Vitamin D levels, lung function, and steroid response in adult asthma. Am J Respir Crit Care Med. 2010 Apr 1;181(7):699-704. doi: 10.1164/rccm.200911-1710OC. Epub 2010 Jan 14.