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)

NCT00565266 | Completed Phase 3 Results DMC

• 10 other identifiers: 547U10HL074206U10HL074208U10HL074073U10HL074227U10HL074225U10HL074204U10HL074218U10HL074212U10HL074231
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• Change Between Week 14 and Week 0 in the Morning (AM) Peak Expiratory Flow (PEF)

  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.

Secondary Outcomes (6)

• Change Between Week 14 and Week 0 in the Forced Expiratory Volume in One Second (FEV1)

  FEV1 was measured on four occasions during each of the three 14-week treatment periods. The primary analysis constructed the change between week 14 and week 0.

• Change Between Week 14 and Week 0 in Asthma Symptoms

  Asthma symptoms were measured daily during each of the three 14-week treatment periods. The primary analysis constructed the change between week 14 and week 0.

• Change Between Week 14 and Week 0 in the Asthma Quality-of-life Questionnaire Score

  The asthma quality-of-life questionnaire score was measured on four occasions during each of the three 14-week treatment periods. The primary analysis constructed the change between week 14 and week 0.

• Change Between Week 14 and Week 0 in the Asthma Control Questionnaire Score

  The asthma control questionnaire score was measured on four occasions during each of the three 14-week treatment periods. The primary analysis constructed the change between week 14 and week 0.

• Change Between Week 14 and Week 0 in the Albuterol Rescue Puffs Per Day

  Albuterol rescue puffs were measured daily during each of the three 14-week treatment periods. The primary analysis constructed the change between week 14 and week 0.

Study Arms (6)

Tio + 1xICS || LABA + 1xICS || 2xICS

EXPERIMENTAL

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; Drug: salmeterol xinafoate; Drug: beclomethasone dipropionate

TIO + 1xICS || 2xICS || LABA + 1xICS

EXPERIMENTAL

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; Drug: salmeterol xinafoate; Drug: beclomethasone dipropionate

LABA + 1xICS || Tio + 1xICS || 2xICS

EXPERIMENTAL

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; Drug: salmeterol xinafoate; Drug: beclomethasone dipropionate

LABA + 1xICS || 2xICS || Tio + 1xICS

EXPERIMENTAL

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; Drug: salmeterol xinafoate; Drug: beclomethasone dipropionate

2xICS || Tio + 1xICS| || LABA + 1xICS

EXPERIMENTAL

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; Drug: salmeterol xinafoate; Drug: beclomethasone dipropionate

2xICS || LABA + 1xICS || Tio + 1xICS

EXPERIMENTAL

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; Drug: salmeterol xinafoate; Drug: beclomethasone dipropionate

Interventions

tiotropium bromide DRUG

tiotropium bromide inhalation powder 18 mcg once daily

Also known as: SPIRIVA® HandiHaler®

2xICS || LABA + 1xICS || Tio + 1xICS; 2xICS || Tio + 1xICS| || LABA + 1xICS; LABA + 1xICS || 2xICS || Tio + 1xICS; LABA + 1xICS || Tio + 1xICS || 2xICS; TIO + 1xICS || 2xICS || LABA + 1xICS; Tio + 1xICS || LABA + 1xICS || 2xICS

salmeterol xinafoate DRUG

salmeterol xinafoate inhalation powder 50 mcg twice daily

Also known as: Serevent® Diskus®

2xICS || LABA + 1xICS || Tio + 1xICS; 2xICS || Tio + 1xICS| || LABA + 1xICS; LABA + 1xICS || 2xICS || Tio + 1xICS; LABA + 1xICS || Tio + 1xICS || 2xICS; TIO + 1xICS || 2xICS || LABA + 1xICS; Tio + 1xICS || LABA + 1xICS || 2xICS

beclomethasone dipropionate DRUG

beclomethasone dipropionate 80 mcg twice daily (1xICS) or 160 mcg twice daily (2xICS)

Also known as: QVAR® Inhalation Aerosol

2xICS || LABA + 1xICS || Tio + 1xICS; 2xICS || Tio + 1xICS| || LABA + 1xICS; LABA + 1xICS || 2xICS || Tio + 1xICS; LABA + 1xICS || Tio + 1xICS || 2xICS; TIO + 1xICS || 2xICS || LABA + 1xICS; Tio + 1xICS || LABA + 1xICS || 2xICS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Beta-agonist reversibility to 4 puffs albuterol of at least 12% OR
• 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:
• Received prescription for or used asthma controller within the 12 months prior to study entry OR
• 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
• 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

You may not qualify if:

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

Sponsors & Collaborators

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

Study Sites (10)

University of California, San Diego

San Diego, California, 92093, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

National Jewish Medical and Research Center

Denver, Colorado, 80206, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Washington University, St. Louis

St Louis, Missouri, 63130, United States

Location

Columbia University Health Sciences

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555, United States

Location

University of Wisconsin, Madison

Madison, Wisconsin, 53706, United States

Location

Related Publications (6)

• 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. doi: 10.1056/NEJMoa1008770. Epub 2010 Sep 19.

  PMID: 20979471 RESULT

• Oba Y, Anwer S, Patel T, Maduke T, Dias S. Addition of long-acting beta2 agonists or long-acting muscarinic antagonists versus doubling the dose of inhaled corticosteroids (ICS) in adolescents and adults with uncontrolled asthma with medium dose ICS: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2023 Aug 21;8(8):CD013797. doi: 10.1002/14651858.CD013797.pub2.

  PMID: 37602534 DERIVED

• Oba Y, Anwer S, Maduke T, Patel T, Dias S. Effectiveness and tolerability of dual and triple combination inhaler therapies compared with each other and varying doses of inhaled corticosteroids in adolescents and adults with asthma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2022 Dec 6;12(12):CD013799. doi: 10.1002/14651858.CD013799.pub2.

  PMID: 36472162 DERIVED

• 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.

  PMID: 28624608 DERIVED

• Peters SP, Bleecker ER, Kunselman SJ, Icitovic N, Moore WC, Pascual R, Ameredes BT, Boushey HA, Calhoun WJ, Castro M, Cherniack RM, Craig T, Denlinger LC, Engle LL, Dimango EA, Israel E, Kraft M, Lazarus SC, Lemanske RF Jr, Lugogo N, Martin RJ, Meyers DA, Ramsdell J, Sorkness CA, Sutherland ER, Wasserman SI, Walter MJ, Wechsler ME, Chinchilli VM, Szefler SJ; National Heart, Lung, and Blood Institute's Asthma Clinical Research Network. Predictors of response to tiotropium versus salmeterol in asthmatic adults. J Allergy Clin Immunol. 2013 Nov;132(5):1068-1074.e1. doi: 10.1016/j.jaci.2013.08.003. Epub 2013 Sep 29.

  PMID: 24084072 DERIVED

• 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.

  PMID: 20075384 DERIVED

Related Links

• Click here for the Asthma Clinical Research Network Web site

MeSH Terms

Conditions

Asthma

Interventions

Tiotropium Bromide; Salmeterol Xinafoate; Beclomethasone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Amines; Phenethylamines; Ethylamines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Chlorinated

Limitations and Caveats

We evaluated only a small number of patients, with no treatment lasting longer than 14 weeks. We could not examine either the rate of asthma exacerbations or long-term safety issues, so our findings cannot be considered clinically directive.

Results Point of Contact

• Title: Vernon M. Chinchilli, PhD
• Organization: Penn State Hershey College of Medicine

vchinchi@psu.edu

717-531-4262

Study Officials

• 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 University Health Sciences

  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

  PRINCIPAL INVESTIGATOR

• Reuben M. Cherniack, MD

  National Jewish Health

  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: November 28, 2007
• First Posted: November 29, 2007
• Study Start: May 1, 2008
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: July 2, 2018
• Results First Posted: April 9, 2013

Record last verified: 2018-05

Locations

US (10)