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) - Full Text View

Sponsor:	National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:	NCT00565266

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 xinofoate Drug: Beclomethasone dipropionate	Phase III

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:

MedlinePlus related topics: Asthma

Drug Information available for: Salmeterol Salmeterol xinafoate Tiotropium bromide Tiotropium Beclomethasone Beclomethasone dipropionate Corticosteroids

U.S. FDA Resources

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:

AM peak expiratory flow (PEF) [ Time Frame: Measured during each of the three 14-week treatment periods ] [ 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: 1 Participants will take part in three 16-week treatment periods, which will occur in the following order: Tiotropium bromide plus a single dose of ICS Long-acting beta-agonist plus a single dose of ICS Double dose of ICS 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.	Drug: Tiotropium bromide Tiotropium bromide inhalation powder (SPIRIVA® HandiHaler®) Other Name: SPIRIVA® HandiHaler® Drug: Salmeterol xinofoate Salmeterol xinofoate inhalation powder bid (Serevent® Diskus® 50 mcg) Other Name: Serevent® Diskus® Drug: Beclomethasone dipropionate Beclomethasone dipropionate 80 mcg bid or 160 mcg bid (QVAR® Inhalation Aerosol) Other Name: QVAR®
Experimental: 2 Participants will take part in three 16-week treatment periods, which will occur in the following order: Tiotropium bromide plus a single dose of ICS Double dose of ICS Long-acting beta-agonist plus a single dose of ICS 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.	Drug: Tiotropium bromide Tiotropium bromide inhalation powder (SPIRIVA® HandiHaler®) Other Name: SPIRIVA® HandiHaler® Drug: Salmeterol xinofoate Salmeterol xinofoate inhalation powder bid (Serevent® Diskus® 50 mcg) Other Name: Serevent® Diskus® Drug: Beclomethasone dipropionate Beclomethasone dipropionate 80 mcg bid or 160 mcg bid (QVAR® Inhalation Aerosol) Other Name: QVAR®
Experimental: 3 Participants will take part in three 16-week treatment periods, which will occur in the following order: Long-acting beta-agonist plus a single dose of ICS Tiotropium bromide plus a single dose of ICS Double dose of ICS 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.	Drug: Tiotropium bromide Tiotropium bromide inhalation powder (SPIRIVA® HandiHaler®) Other Name: SPIRIVA® HandiHaler® Drug: Salmeterol xinofoate Salmeterol xinofoate inhalation powder bid (Serevent® Diskus® 50 mcg) Other Name: Serevent® Diskus® Drug: Beclomethasone dipropionate Beclomethasone dipropionate 80 mcg bid or 160 mcg bid (QVAR® Inhalation Aerosol) Other Name: QVAR®
Experimental: 4 Participants will take part in three 16-week treatment periods, which will occur in the following order: Long-acting beta-agonist plus a single dose of ICS Double dose of ICS Tiotropium bromide plus a single dose of ICS 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.	Drug: Tiotropium bromide Tiotropium bromide inhalation powder (SPIRIVA® HandiHaler®) Other Name: SPIRIVA® HandiHaler® Drug: Salmeterol xinofoate Salmeterol xinofoate inhalation powder bid (Serevent® Diskus® 50 mcg) Other Name: Serevent® Diskus® Drug: Beclomethasone dipropionate Beclomethasone dipropionate 80 mcg bid or 160 mcg bid (QVAR® Inhalation Aerosol) Other Name: QVAR®
Experimental: 5 Participants will take part in three 16-week treatment periods, which will occur in the following order: Double dose of ICS Tiotropium bromide plus a single dose of ICS Long-acting beta-agonist plus a single dose of ICS 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.	Drug: Tiotropium bromide Tiotropium bromide inhalation powder (SPIRIVA® HandiHaler®) Other Name: SPIRIVA® HandiHaler® Drug: Salmeterol xinofoate Salmeterol xinofoate inhalation powder bid (Serevent® Diskus® 50 mcg) Other Name: Serevent® Diskus® Drug: Beclomethasone dipropionate Beclomethasone dipropionate 80 mcg bid or 160 mcg bid (QVAR® Inhalation Aerosol) Other Name: QVAR®
Experimental: 6 Participants will take part in three 16-week treatment periods, which will occur in the following order: Double dose of ICS Long-acting beta-agonist plus a single dose of ICS Tiotropium bromide plus a single dose of ICS 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.	Drug: Tiotropium bromide Tiotropium bromide inhalation powder (SPIRIVA® HandiHaler®) Other Name: SPIRIVA® HandiHaler® Drug: Salmeterol xinofoate Salmeterol xinofoate inhalation powder bid (Serevent® Diskus® 50 mcg) Other Name: Serevent® Diskus® Drug: Beclomethasone dipropionate Beclomethasone dipropionate 80 mcg bid or 160 mcg bid (QVAR® Inhalation Aerosol) Other Name: QVAR®

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 plus a single dose of ICS
Long-acting beta-agonist plus a single dose of ICS
Double dose of ICS

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
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 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 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 A.M. 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

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

National Heart, Lung, and Blood Institute (NHLBI)

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, St. Louis
Principal Investigator:	Emily A. DiMango, MD	Columbia University
Principal Investigator:	Stephen P. Peters, MD, PhD	Wake Forest University
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:

Click here for the Asthma Clinical Research Network Web site This link exits the ClinicalTrials.gov site

No publications provided by National Heart, Lung, and Blood Institute (NHLBI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Peters SP, Kunselman SJ, Icitovic N, Moore WC, Pascual R, Ameredes BT, Boushey HA, Calhoun WJ, Castro M, Cherniack RM, Craig T, Denlinger L, Engle LL, DiMango EA, Fahy JV, Israel E, Jarjour N, Kazani SD, Kraft M, Lazarus SC, Lemanske RF Jr, Lugogo N, Martin RJ, Meyers DA, Ramsdell J, Sorkness CA, Sutherland ER, Szefler SJ, Wasserman SI, Walter MJ, Wechsler ME, Chinchilli VM, Bleecker ER; National Heart, Lung, and Blood Institute Asthma Clinical Research Network. Tiotropium bromide step-up therapy for adults with uncontrolled asthma. N Engl J Med. 2010 Oct 28;363(18):1715-26.

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. Epub 2010 Jan 14.

Responsible Party:	Vernon M. Chinchilli, PhD, Pennsylvania State University, College of Medicine
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, U10 HL074231
Study First Received:	November 28, 2007
Last Updated:	September 17, 2010
Health Authority:	United States: Federal Government

Additional relevant MeSH terms:

Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Beclomethasone
Salmeterol
Tiotropium
Bromides
Anti-Inflammatory Agents
Therapeutic Uses

Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Anticonvulsants
Central Nervous System Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 12, 2012