Tiotropium for Smoking Asthmatics Study
Tiotropium for Smoking Asthmatics Study
The study's research questions concern the appropriateness of use of tiotropium for patients
 with asthma who are current smokers. It is suggested that patients with asthma who smoke, may
 in fact share similarities with patients with chronic obstructive pulmonary disease (COPD).
 Because of this, the study will determine whether this sub-group of patients would in fact
 benefit from therapy currently approved and marketed for COPD patients.
The study is designed as an open label cross-over study. Ethical approval will be obtained
 from both the University of Alberta Health Research Ethics Board and the University of
 Saskatchewan Health Research Ethics Board.

 Following informed consent, we will obtain pulmonary function testing in all subjects. If
 subject is currently prescribed a long acting beta agonist (LABA) it will be stopped before
 continuing with the study and the subject, as with all subjects, will be re-assessed after
 two weeks. We will also measure exhaled NO (eNO) using standards established by the American
 Thoracic Society. Additionally we will obtain a urine sample which will be frozen and stored
 for subsequent metabolite profiling by NMR spectroscopy. Subjects currently prescribed LABA's
 will have testing done two weeks after stopping medication.

 We will obtain routine demographic information including age, sex, and usual asthma
 medication usage. We will also obtain health related quality of life status using generic
 (15D) and disease specific (Asthma Quality of Life) questionnaires. Subjects will be
 instructed regarding use of peak flow meters and the typical symptoms associated with loss of
 asthma control. They will be instructed regarding accessing a dedicated asthma website (the
 Virtual Asthma Clinic) that incorporates the above questions. There is also a place for
 subjects to enter twice daily peak flow measurements. The website is password protected and
 each subject can access only their own individualized data entry pages. A research
 coordinator is able to access any subject data again using a unique password. We will use
 this internet-based program to monitor daily PEF, daily asthma symptoms and asthma-related
 quality of life. Patients will be instructed to access the website daily and will be
 re-assessed at two weeks. Subjects will be instructed to continue with their usual asthma
 management and to log on to the asthma website daily to record symptoms and twice daily peak
 flows. Peak flows will consist of pre-bronchodilator peak expiratory flow taken in the
 morning and in the evening. Only subjects meeting criteria for well controlled asthma (GOAL
 criteria) along with objective compliance with study protocols over the two weeks will then
 be enrolled in the next phase of the study.

 For the next two weeks of the study, subjects will be randomly allocated to take either their
 regularly prescribed inhaled corticosteroid (ICS) and a long acting beta agonist (LABA) or
 their regularly prescribed ICS and tiotropium. At the end of this period all subjects will
 return for spirometry, urine sampling and for measurement eNO. This will be followed by a two
 week wash-out period when all subjects will take only their inhaled corticosteroid (ICS). For
 the subsequent two weeks the subject will take the treatment they did not receive in the
 first two weeks. At the end of this period all subjects will again return for spirometry,
 urine sampling and for measurement of eNO. During a fifth period of two weeks duration,
 subjects will take both the LABA and tiotropium. Subjects will then return for final
 measurement of spirometry, urine sampling and eNO.

 Subjects showing variability of symptoms consistent with poor asthma control, will be
 referred back to their treating physicians with their clinical information. All subjects will
 be instructed to return to their medication regimen that was initiated by their physician
 prior to the study.

 If subjects experience a clinical exacerbation, they will be instructed to return to their
 test site. They will be instructed to increase their controller medication and to continue
 with the increased steroid phase of the study. Any subject experiencing a severe asthma
 exacerbation (described below) will be withdrawn from the study. Assuming approximately 30%
 severe exacerbation rate per year in this population, we would anticipate that one to two
 patients would normally experience a severe exacerbation over a 10 week course. If four of
 our subjects experience severe exacerbations, we will hold the trial and have an external
 review of the unblinded data. This will include review of patient compliance with study
 protocols. If the exacerbations are all in the tiotropium group we will stop the study. We
 anticipate with the use of the on-line data collection tool (VAC), the study coordinators
 will be able to see any exacerbation developing at an early point and that we will be able to
 effectively intervene to prevent severe exacerbations.

 A mild clinical exacerbation will be defined by any one of the following events:

 1. A decrease in peak flow to less than 80% of best effort for two consecutive days.

 2. An increase in reliever medication (fast acting beta agonist) by 50% over baseline needs
 for two consecutive days.

 3. Waking at night due to asthma on two consecutive nights. A severe exacerbation will be
 defined as any need for additional medical contact for treatment of asthma (e.g.,
 emergency room, walk-in clinic) or any hospital admission for asthma. The need for oral
 corticosteroids will also constitute a severe exacerbation. If at any point the subjects
 undergo a severe exacerbation, they will be examined by either their own treating
 physician or by one of the physicians associated with this study and appropriate
 escalation of treatment will be commenced. The HREB will be informed of all severe
 exacerbations. The study coordinator and one of the study physicians will be available
 by pager during the course of the study.
Inclusion Criteria:

 -  Male or female patient with a working diagnosis of asthma by clinical presentation or
 by spirometry testing results.

 -  Currently prescribed inhaled corticosteroids (ICS) for the treatment of asthma, and
 may or may not be prescribed additional therapies for asthma.

 -  Is a current smoker with a minimum of a five year history of smoking.

 -  Provides written informed consent.

 Exclusion Criteria:

 -  Has a diagnosis of COPD.

 -  Is currently enrolled in another clinical trial.

 -  Has any condition which, may decrease the chance of obtaining satisfactory data to
 achieve the objectives of the study.

 -  Is unable to provide written informed consent.