AsthmaPhase 3TALCNCT00565266
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)
A Phase 3 study testing tiotropium bromide, salmeterol xinafoate and beclomethasone dipropionate in people with Asthma, run by Milton S. Hershey Medical Center at 10 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Asthma
- What is being tested?
- tiotropium bromide, salmeterol xinafoate and beclomethasone dipropionate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 210 participants
- Where
- 10 sitesUnited States
- Study dates
- May 2008to May 2010
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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
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- 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
- 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.)
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Brigham & Women's Hospital
Boston, Massachusetts, 02115
National Jewish Medical and Research Center
Denver, Colorado, 80206
Duke University Medical Center
Durham, North Carolina, 27710
University of Texas Medical Branch
Galveston, Texas, 77555
University of Wisconsin, Madison
Madison, Wisconsin, 53706
Columbia University Health Sciences
New York, New York, 10032
University of California, San Diego
San Diego, California, 92093
University of California, San Francisco
San Francisco, California, 94143
Washington University, St. Louis
St Louis, Missouri, 63130
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
About this study
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.
Read the 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.
- Conditions
- Asthma
- Being tested
- tiotropium bromide, salmeterol xinafoate, beclomethasone dipropionate
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tiotropium bromideDrug
Also called SPIRIVA® HandiHaler®
tiotropium bromide inhalation powder 18 mcg once daily
salmeterol xinafoateDrug
Also called Serevent® Diskus®
salmeterol xinafoate inhalation powder 50 mcg twice daily
beclomethasone dipropionateDrug
Also called QVAR® Inhalation Aerosol
beclomethasone dipropionate 80 mcg twice daily (1xICS) or 160 mcg twice daily (2xICS)
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: 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). Receives: 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). Receives: 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). Receives: 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). Receives: Drug: tiotropium bromide; Drug: salmeterol xinafoate; Drug: beclomethasone dipropionate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change Between Week 14 and Week 0 in the Morning (AM) Peak Expiratory Flow (PEF)
Measured: 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)
Measured: 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 recorded as 0 (absent = no symptom )
- (mild = symptom was minimally troublesome, i.e. not sufficient to interfere with normal daily activity or sleep)
- (moderate = symptom was sufficiently troublesome to interfere with normal daily activity or sleep)
- (severe = symptom was so severe as to prevent normal activity and/or sleep )
Measured: 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
Scores on the Asthma Quality-of-Life Questionnaire range from 1 to 7, with a higher score indicating a better quality of life.
Measured: 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
Scores on the Asthma Control Questionnaire range from 0 to 6, with a higher score indicating worse asthma control.
Measured: 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
Total number of puffs from the albuterol (rescue) inhaler during the previous 24 hours (excluding those puffs for preventive use).
Measured: 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.
Change Between Week 14 and Week 0 in the Proportion of Asthma Control Days
An asthma control day was defined as a day in which there were no symptoms and no albuterol (rescue) puffs.
Measured: An asthma control day was determined daily during each of the three 14-week treatment periods. The primary analysis constructed the change between week 14 and week 0.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2007 (estimated)
- Study startMay 2008
- Primary completionMay 2010
- Study completionMay 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by Milton S. Hershey Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 210 participants (actual)
Sponsor and investigators
- Lead sponsor
- Milton S. Hershey Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Vernon M. Chinchilli, PhD, Milton S. Hershey Medical Center
- Investigators
- Homer A. Boushey, MD, Principal investigator, University of California, San FranciscoRichard J. Martin, MD, Principal investigator, National Jewish HealthElliot Israel, MD, Principal investigator, Brigham and Women's HospitalStephen I. Wasserman, MD, Principal investigator, University of California, San DiegoMario Castro, MD, Principal investigator, Washington University School of MedicineEmily A. DiMango, MD, Principal investigator, Columbia UniversityStephen P. Peters, MD, PhD, Principal investigator, Wake Forest University Health SciencesMonica Kraft, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00565266
- Sponsor's protocol ID
- 547
- Other IDs
- U10HL074206, U10HL074208, U10HL074073, U10HL074227, U10HL074225, U10HL074204, U10HL074218, U10HL074212
- Acronym
- TALC
- Status last verified
- May 2018
- First submitted
- 28 Nov 2007
- Last updated
- 2 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 20979471Oba 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.
PubMed 37602534Oba 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.
PubMed 36472162Lugogo 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.
PubMed 28624608Peters 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.
PubMed 24084072Sutherland 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.
PubMed 20075384
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00565266
- Acronym / sponsor ID
- TALC / 547
- Conditions
- Asthma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 210 participants (actual)
- Lead sponsor
- Milton S. Hershey Medical CenterUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- May 2008
- Primary completion
- May 2010 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 29 Nov 2007 (estimated)
- Results
- Posted 9 Apr 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Tio + 1xICS || LABA + 1xICS || 2xICS | Experimental | Drug: tiotropium bromide, Drug: salmeterol xinafoate, Drug: beclomethasone dipropionateParticipants 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). |
| TIO + 1xICS || 2xICS || LABA + 1xICS | Experimental | Drug: tiotropium bromide, Drug: salmeterol xinafoate, Drug: beclomethasone dipropionateParticipants 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). |
| LABA + 1xICS || Tio + 1xICS || 2xICS | Experimental | Drug: tiotropium bromide, Drug: salmeterol xinafoate, Drug: beclomethasone dipropionateParticipants 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). |
| LABA + 1xICS || 2xICS || Tio + 1xICS | Experimental | Drug: tiotropium bromide, Drug: salmeterol xinafoate, Drug: beclomethasone dipropionateParticipants 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). |
| 2xICS || Tio + 1xICS| || LABA + 1xICS | Experimental | Drug: tiotropium bromide, Drug: salmeterol xinafoate, Drug: beclomethasone dipropionateParticipants 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). |
| 2xICS || LABA + 1xICS || Tio + 1xICS | Experimental | Drug: tiotropium bromide, Drug: salmeterol xinafoate, Drug: beclomethasone dipropionateParticipants 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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:
- 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:
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| tiotropium bromideAlso: SPIRIVA® HandiHaler®tiotropium bromide inhalation powder 18 mcg once daily | Drug | 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 xinafoateAlso: Serevent® Diskus®salmeterol xinafoate inhalation powder 50 mcg twice daily | Drug | 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 dipropionateAlso: QVAR® Inhalation Aerosolbeclomethasone dipropionate 80 mcg twice daily (1xICS) or 160 mcg twice daily (2xICS) | Drug | 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 |
Primary outcome
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.
6 secondary outcomes
Change Between Week 14 and Week 0 in the Forced Expiratory Volume in One Second (FEV1)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Change Between Week 14 and Week 0 in the Proportion of Asthma Control Days
Time frame: An asthma control day was determined daily during each of the three 14-week treatment periods. The primary analysis constructed the change between week 14 and week 0.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20979471Peters 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.
- Derived from this study: PubMed 37602534Oba 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.
- Derived from this study: PubMed 36472162Oba 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.
- Derived from this study: PubMed 28624608Lugogo 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.
- Derived from this study: PubMed 24084072Peters 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.
- Derived from this study: PubMed 20075384Sutherland 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.
- Click here for the Asthma Clinical Research Network Web siteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Homer A. Boushey, MD principal investigator
University of California, San Francisco
Richard J. Martin, MD principal investigator
National Jewish Health
Elliot Israel, MD principal investigator
Brigham and Women's Hospital
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing tiotropium bromide, salmeterol xinafoate and beclomethasone dipropionate in people with Asthma, run by Milton S. Hershey Medical Center at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Apr 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00565266, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2018.