Asthma Clinical Research Network (ACRN) Trial - Tiotropium Bromide as an Alternative to Increased Inhaled Corticosteroid in Patients Inadequately Controlled on a Lower Dose of Inhaled Corticosteroid (TALC)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Vernon M. Chinchilli, PhD, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier:
NCT00565266
First received: November 28, 2007
Last updated: April 5, 2013
Last verified: April 2013
  Purpose

Typically, people with asthma are initially prescribed a low dose of inhaled corticosteroid (ICS) medication to control asthma symptoms. If a low dose of ICS is ineffective at controlling symptoms, the addition of a second controller medication is recommended. This study will examine the effectiveness of the medication tiotropium bromide combined with a low dose of ICS at maintaining asthma control in people with moderately severe asthma.


Condition Intervention Phase
Asthma
Drug: tiotropium bromide
Drug: salmeterol xinafoate
Drug: beclomethasone dipropionate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Asthma Clinical Research Network (ACRN) Trial - Tiotropium Bromide as an Alternative to Increased Inhaled Corticosteroid in Patients Inadequately Controlled on a Lower Dose of Inhaled Corticosteroid (TALC)

Resource links provided by NLM:


Further study details as provided by Milton S. Hershey Medical Center:

Primary Outcome Measures:
  • Change Between Week 14 and Week 0 in the Morning (AM) Peak Expiratory Flow (PEF) [ Time Frame: AM PEF was measured daily during each of the three 14-week treatment periods. The primary analysis constructed the change between week 14 and week 0. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Forced Expiratory Volume in One Second (FEV1) [ Time Frame: Measured during each of the three 14-week treatment periods ] [ Designated as safety issue: No ]
  • Asthma Symptoms, Number of Asthma-control Days, Rescue Inhaler Use [ Time Frame: Measured during each of the three 14-week treatment periods ] [ Designated as safety issue: No ]
  • Asthma Control, Asthma Quality-of-life [ Time Frame: Measured during each of the three 14-week treatment periods ] [ Designated as safety issue: No ]
  • Asthma Exacerbations [ Time Frame: Measured during each of the three 14-week treatment periods ] [ Designated as safety issue: No ]
  • Biomarkers of Inflammation and Oxidative Stress [ Time Frame: Measured during each of the three 14-week treatment periods ] [ Designated as safety issue: No ]
  • Adverse Events [ Time Frame: Measured during each of the three 14-week treatment periods ] [ Designated as safety issue: Yes ]

Enrollment: 210
Study Start Date: May 2008
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tio + 1xICS || LABA + 1xICS || 2xICS

Participants will take part in three 16-week treatment periods, which will occur in the following order:

  • tiotropium bromide inhalation powder 18 mcg once daily (Tio) plus beclomethasone dipropionate 80 mcg twice daily (1xICS)
  • salmeterol xinafoate inhalation powder 50 mcg twice daily (LABA) plus beclomethasone dipropionate 80 mcg twice daily (1xICS)
  • beclomethasone dipropionate 160 mcg twice daily (2xICS)

Each of the three 16-week treatment periods will consist of 14 weeks of treatment followed by a 2-week washout period, in which participants will receive beclomethasone dipropionate 80 mcg twice daily (1xICS).

Drug: tiotropium bromide
tiotropium bromide inhalation powder 18 mcg once daily
Other Name: SPIRIVA® HandiHaler®
Drug: salmeterol xinafoate
salmeterol xinafoate inhalation powder 50 mcg twice daily
Other Name: Serevent® Diskus®
Drug: beclomethasone dipropionate
beclomethasone dipropionate 80 mcg twice daily (1xICS) or 160 mcg twice daily (2xICS)
Other Name: QVAR® Inhalation Aerosol
Experimental: TIO + 1xICS || 2xICS || LABA + 1xICS

Participants will take part in three 16-week treatment periods, which will occur in the following order:

  • tiotropium bromide inhalation powder 18 mcg once daily (Tio) plus beclomethasone dipropionate 80 mcg twice daily (1xICS)
  • beclomethasone dipropionate 160 mcg twice daily (2xICS)
  • salmeterol xinafoate inhalation powder 50 mcg twice daily (LABA) plus beclomethasone dipropionate 80 mcg twice daily (1xICS)

Each of the three 16-week treatment periods will consist of 14 weeks of treatment followed by a 2-week washout period, in which participants will receive beclomethasone dipropionate 80 mcg twice daily (1xICS).

Drug: tiotropium bromide
tiotropium bromide inhalation powder 18 mcg once daily
Other Name: SPIRIVA® HandiHaler®
Drug: salmeterol xinafoate
salmeterol xinafoate inhalation powder 50 mcg twice daily
Other Name: Serevent® Diskus®
Drug: beclomethasone dipropionate
beclomethasone dipropionate 80 mcg twice daily (1xICS) or 160 mcg twice daily (2xICS)
Other Name: QVAR® Inhalation Aerosol
Experimental: LABA + 1xICS || Tio + 1xICS || 2xICS

Participants will take part in three 16-week treatment periods, which will occur in the following order:

  • salmeterol xinafoate inhalation powder 50 mcg twice daily (LABA) plus beclomethasone dipropionate 80 mcg twice daily (1xICS)
  • tiotropium bromide inhalation powder 18 mcg once daily (Tio) plus beclomethasone dipropionate 80 mcg twice daily (1xICS)
  • beclomethasone dipropionate 160 mcg twice daily (2xICS)

Each of the three 16-week treatment periods will consist of 14 weeks of treatment followed by a 2-week washout period, in which participants will receive beclomethasone dipropionate 80 mcg twice daily (1xICS).

Drug: tiotropium bromide
tiotropium bromide inhalation powder 18 mcg once daily
Other Name: SPIRIVA® HandiHaler®
Drug: salmeterol xinafoate
salmeterol xinafoate inhalation powder 50 mcg twice daily
Other Name: Serevent® Diskus®
Drug: beclomethasone dipropionate
beclomethasone dipropionate 80 mcg twice daily (1xICS) or 160 mcg twice daily (2xICS)
Other Name: QVAR® Inhalation Aerosol
Experimental: LABA + 1xICS || 2xICS || Tio + 1xICS

Participants will take part in three 16-week treatment periods, which will occur in the following order:

  • salmeterol xinafoate inhalation powder 50 mcg twice daily (LABA) plus beclomethasone dipropionate 80 mcg twice daily (1xICS)
  • beclomethasone dipropionate 160 mcg twice daily (2xICS)
  • tiotropium bromide inhalation powder 18 mcg once daily (Tio) plus beclomethasone dipropionate 80 mcg twice daily (1xICS)

Each of the three 16-week treatment periods will consist of 14 weeks of treatment followed by a 2-week washout period, in which participants will receive beclomethasone dipropionate 80 mcg twice daily (1xICS).

Drug: tiotropium bromide
tiotropium bromide inhalation powder 18 mcg once daily
Other Name: SPIRIVA® HandiHaler®
Drug: salmeterol xinafoate
salmeterol xinafoate inhalation powder 50 mcg twice daily
Other Name: Serevent® Diskus®
Drug: beclomethasone dipropionate
beclomethasone dipropionate 80 mcg twice daily (1xICS) or 160 mcg twice daily (2xICS)
Other Name: QVAR® Inhalation Aerosol
Experimental: 2xICS || Tio + 1xICS| || LABA + 1xICS

Participants will take part in three 16-week treatment periods, which will occur in the following order:

  • beclomethasone dipropionate 160 mcg twice daily (2xICS)
  • tiotropium bromide inhalation powder 18 mcg once daily (Tio) plus beclomethasone dipropionate 80 mcg twice daily (1xICS)
  • salmeterol xinafoate inhalation powder 50 mcg twice daily (LABA) plus beclomethasone dipropionate 80 mcg twice daily (1xICS)

Each of the three 16-week treatment periods will consist of 14 weeks of treatment followed by a 2-week washout period, in which participants will receive beclomethasone dipropionate 80 mcg twice daily (1xICS).

Drug: tiotropium bromide
tiotropium bromide inhalation powder 18 mcg once daily
Other Name: SPIRIVA® HandiHaler®
Drug: salmeterol xinafoate
salmeterol xinafoate inhalation powder 50 mcg twice daily
Other Name: Serevent® Diskus®
Drug: beclomethasone dipropionate
beclomethasone dipropionate 80 mcg twice daily (1xICS) or 160 mcg twice daily (2xICS)
Other Name: QVAR® Inhalation Aerosol
Experimental: 2xICS || LABA + 1xICS || Tio + 1xICS

Participants will take part in three 16-week treatment periods, which will occur in the following order:

  • beclomethasone dipropionate 160 mcg twice daily (2xICS)
  • salmeterol xinafoate inhalation powder 50 mcg twice daily (LABA) plus beclomethasone dipropionate 80 mcg twice daily (1xICS)
  • tiotropium bromide inhalation powder 18 mcg once daily (Tio) plus beclomethasone dipropionate 80 mcg twice daily (1xICS)

Each of the three 16-week treatment periods will consist of 14 weeks of treatment followed by a 2-week washout period, in which participants will receive beclomethasone dipropionate 80 mcg twice daily (1xICS).

Drug: tiotropium bromide
tiotropium bromide inhalation powder 18 mcg once daily
Other Name: SPIRIVA® HandiHaler®
Drug: salmeterol xinafoate
salmeterol xinafoate inhalation powder 50 mcg twice daily
Other Name: Serevent® Diskus®
Drug: beclomethasone dipropionate
beclomethasone dipropionate 80 mcg twice daily (1xICS) or 160 mcg twice daily (2xICS)
Other Name: QVAR® Inhalation Aerosol

Detailed Description:

National and international asthma treatment guidelines recommend ICS as the initial controller therapy for people with asthma who are in need of daily treatment with a controller medication. If treatment with low to moderate doses of ICS is not sufficient to gain and maintain asthma control, current guidelines recommend adding a second controller medication rather than increasing the dose of ICS. Current options for the second medication include a long-acting beta-agonist, a leukotriene modifier, or theophylline. It is possible that other medications, not yet tested, could fill the role of the second controller medication. Tiotropium bromide is a medication that is used to treat chronic obstructive pulmonary disease (COPD). It works by relaxing and opening the air passages to the lungs to make breathing easier. For people with asthma, the addition of tiotropium bromide may be a good option as a second controller medication. The purpose of this study is to determine if combining tiotropium bromide with a low dose of ICS is more effective than doubling the dose of ICS in people with moderately severe asthma. This study will also examine whether the addition of tiotropium bromide to low dose ICS is as effective as the addition of a long-acting beta-agonist at maintaining asthma control.

This study will begin with a 4-week run-in period during which participants will be monitored while they use an inhaler containing a low dose of ICS medication. Next, participants will be assigned to take part in either the TALC study or the Best Adjustment Strategy for Asthma in Long Term (BASALT) study, which is a separate Asthma Clinical Research Network (ACRN) study.

All TALC participants will then undergo three 16-week treatment periods, which will include the following:

  • tiotropium bromide inhalation powder 18 mcg once daily (Tio) plus beclomethasone dipropionate 80 mcg twice daily (1xICS)
  • salmeterol xinafoate inhalation powder 50 mcg twice daily (LABA) plus beclomethasone dipropionate 80 mcg twice daily (1xICS)
  • beclomethasone dipropionate 160 mcg twice daily (2xICS)

The order in which the three treatment periods will occur will be randomly assigned for each participant. Each of the three 16-week treatment periods will consist of 14 weeks of treatment followed by a 2-week washout period, in which participants will receive a single does of ICS. Study visits will occur at baseline and Weeks 2 and 4 of the 4-week run-in period, and at Weeks 4, 9, 14, and 16 of each 16-week treatment period. Spirometry tests to measure lung function will occur at each study visit and exhaled nitric oxide testing and questionnaires to assess asthma control and symptoms will occur at most visits. During study visits at Week 4 of the run-in period and Week 14 of each treatment period, lung function measurements, sputum collection, questionnaires to assess asthma quality-of-life, and measurements of sleep and daytime alertness will all occur. Participants will also record asthma symptoms, peak flow measurements, and medication usage in a daily diary.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria for TALC and BASALT 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) of 8 milligrams per milliliter (mg/mL) or less when not on an inhaled corticosteroid (ICS), or 16 mg/mL or less when on an ICS
  • Need for daily controller therapy (i.e., ICS, 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 TALC Study:

  • Ability to measure morning (AM) peak expiratory flow (PEF) on schedule using electronic peak flow meter (EPFM) and to complete the study diary correctly at least 75% of the time during the interval between Weeks 2 and 4 of the run-in period
  • Adherence with study medication dosing at least 75% of the time during the interval between Weeks 2 and 4 of the run-in period
  • No asthma exacerbation requiring use of oral corticosteroids or additional asthma medications (including an increased dose of ICS) during the run-in period
  • FEV1 greater than 40% of the predicted value

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 asthma exacerbation 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 TALC Study:

  • Inability to coordinate use of the medication delivery devices used in the study, based on the opinion of the investigator or clinical coordinator
  • Presence at Week 4 of the run-in period of any of the exclusion criteria stipulated for Week 0 of the run-in period (Note: Respiratory tract infections that do not cause the participant to meet exacerbation criteria are not considered exclusionary.)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00565266

Locations
United States, California
University of California, San Diego
San Diego, California, United States, 92093
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Colorado
National Jewish Medical and Research Center
Denver, Colorado, United States, 80206
United States, Massachusetts
Brigham & Women's Hospital
Boston, Massachusetts, United States, 02115
United States, Missouri
Washington University, St. Louis
St. Louis, Missouri, United States, 63130
United States, New York
Columbia University Health Sciences
New York, New York, United States, 10032
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Texas
University of Texas Medical Branch
Galveston, Texas, United States, 77555
United States, Wisconsin
University of Wisconsin, Madison
Madison, Wisconsin, United States, 53706
Sponsors and Collaborators
Milton S. Hershey Medical Center
Investigators
Principal Investigator: Homer A. Boushey, MD University of California, San Francisco
Principal Investigator: Richard J. Martin, MD National Jewish Health
Principal Investigator: Elliot Israel, MD Brigham and Women's Hospital
Principal Investigator: Stephen I. Wasserman, MD University of California, San Diego
Principal Investigator: Mario Castro, MD Washington University School of Medicine
Principal Investigator: Emily A. DiMango, MD Columbia University
Principal Investigator: Stephen P. Peters, MD, PhD Wake Forest School of Medicine
Principal Investigator: Monica Kraft, MD Duke University
Principal Investigator: William J. Calhoun, MD University of Texas
Principal Investigator: Robert F. Lemanske, MD University of Wisconsin, Madison
Study Chair: Reuben M. Cherniack, MD National Jewish Health
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Vernon M. Chinchilli, PhD, Professor and Chair, Department of Public Health Sciences, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier: NCT00565266     History of Changes
Other Study ID Numbers: 547, U10 HL074206, U10 HL074208, U10 HL074073, U10 HL074227, U10 HL074225, U10 HL074204, U10 HL074218, U10 HL074212, U10HL074231
Study First Received: November 28, 2007
Results First Received: April 30, 2012
Last Updated: April 5, 2013
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Lung Diseases
Lung Diseases, Obstructive
Respiratory Hypersensitivity
Respiratory Tract Diseases
Albuterol
Beclomethasone
Bromides
Salmeterol
Tiotropium
Adrenergic Agents
Adrenergic Agonists
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Anti-Asthmatic Agents
Anti-Inflammatory Agents
Anticonvulsants
Autonomic Agents
Bronchodilator Agents
Central Nervous System Agents
Cholinergic Agents
Cholinergic Antagonists
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 29, 2014