Clinical trial NCT00565266
Conditions: Asthma
Sponsor: Milton S. Hershey Medical Center
Start date: 2008-05-01; Completion date: 2010-05-01
Enrollment: 210 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

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.

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.

Arms: arm 1: 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). arm 2: 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). arm 3: 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). arm 4: 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). arm 5: 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). arm 6: 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).
Interventions: intervention 1: tiotropium bromide intervention 2: salmeterol xinafoate intervention 3: beclomethasone dipropionate
Intervention descriptions: intervention 1: tiotropium bromide inhalation powder 18 mcg once daily intervention 2: salmeterol xinafoate inhalation powder 50 mcg twice daily intervention 3: beclomethasone dipropionate 80 mcg twice daily (1xICS) or 160 mcg twice daily (2xICS)

Protocol documents: