Evaluation of Tiotropium 5 µg/Day Delivered Via the Respimat® Inhaler Over 48 Weeks in Patients With Severe Persistent Asthma on Top of Usual Care (Study I)
Condition: Asthma
MeSH terms: Asthma
Intervention: tiotropium 5mcg/day; placebo
Intervention description: Intervention = randomisation: Patient to receive double-blind treatment with either 5mcg/day tiotropium inhalation solution or placebo; Matching placebo
Intervention MeSH terms: Tiotropium Bromide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 459.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The trial is a randomised, double-blind, placebo-controlled, parallel-group trial to evaluate
      the efficacy and safety of 5 µg tiotropium over a 48-week treatment period as compared to
      placebo. Tiotropium inhalation solution delivered by the Respimat® inhaler will be examined
      as add-on controller therapy on top of usual care in patients with severe persistent asthma.

      The primary objective of each trial is to evaluate the long term efficacy of tiotropium over
      placebo on top of usual care in patients with severe persistent asthma as determined by
      pulmonary function testing, effects on asthma exacerbations, effects on quality of life, on
      asthma control and health care resource utilisation. The secondary objective of each trial is
      to compare the long term safety of tiotropium with placebo in this patient population.
    

Eligibility criteria:

        Inclusion criteria:

          1. All patients must sign and date an Informed Consent Form consistent with ICH-GCP
             guidelines and local legislation prior to participation in the trial (i.e. prior to
             any trial procedures, including any pre-trial washout of medications and medication
             restrictions for pulmonary function test at Visit 1).

          2. Male or female patients aged at least 18 years but not more than 75 years.

          3. All patients must have at least a 5-year history of asthma at the time of enrolment
             into the trial and the diagnosis of asthma must have been made before the patient´s
             age of 40.

          4. All patients must have a diagnosis of severe persistent asthma and must be symptomatic
             despite treatment with high, stable doses of inhaled corticosteroids and a long-acting
             beta adrenergic agent

          5. All patients must have a history of one or more asthma exacerbation in the past year.

          6. Patients must have evidence of treated, severe, persistent asthma in
             postbronchodilatory pulmonary function tests.

          7. Patients should be never-smokers or ex-smokers who stopped smoking at least one year
             prior to enrolment and who have a smoking history of less than 10 pack years

          8. Patients must be able to use the Respimat® inhaler correctly

          9. Patients must be able to perform all trial related procedures including technically
             acceptable pulmonary function tests and use of the electronic diary/peak flow meter.

        Exclusion criteria:

          1. Patients with a significant disease other than asthma. A significant disease is
             defined as a disease which, in the opinion of the investigator, may (i) put the
             patient at risk because of participation in the trial, or (ii) influence the results
             of the trial, or (iii) cause concern regarding the patient´s ability to participate in
             the trial.

          2. Patients with clinically relevant abnormal screening haematology or blood chemistry.

          3. Patients with a recent history (i.e. six months or less) of myocardial infarction,
             hospitalisation for cardiac failure during the past year, any unstable or life
             threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a
             change in drug therapy within the past year, known active tuberculosis, malignancy for
             which the patient has undergone resection, radiation therapy or chemotherapy within
             the last five years (treated basal cell carcinoma allowed), lung diseases other than
             asthma (e.g. COPD), significant alcohol or drug abuse within the past two years,
             patients who have undergone thoracotomy with pulmonary resection. Patients with a
             history of thoracotomy for other reasons should be evaluated as per exclusion
             criterion No. 1.

          4. Patients who are currently in a pulmonary rehabilitation program or have completed a
             pulmonary rehabilitation program in the 6 weeks prior to the screening visit (Visit
             1).

          5. Patients using oral corticosteroid medication at stable doses exceeding 5 mg
             prednisolone or prednisolone equivalent every day or 10 mg prednisolone or
             prednisolone equivalent every second day.

          6. Patients with known hypersensitivity to anticholinergic drugs, BAC, EDTA or any other
             components of the tiotropium inhalation solution.

          7. Pregnant or nursing women or women of childbearing potential not using a highly
             effective method of birth control. Female patients will be considered to be of
             childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal
             ligation/salpingectomy, or post-menopausal for at least two years.

          8. Patients who have taken an investigational drug within four weeks or six half-lives
             (whichever is greater) prior to Visit 1.

          9. Patients who have been treated with the long-acting anticholinergic tiotropium
             (Spiriva®), beta-blocker medication, oral beta-adrenergics, other non-approved and
             according to international guidelines not recommended ´experimental´ drugs for routine
             asthma therapy (e.g. TNF-alpha blockers, methotrexate, cyclosporin) within four weeks
             prior to the Screening Visit (Visit 1) or during the screening period.

         10. Patients with any asthma exacerbation or respiratory tract infection in the four weeks
             prior to the trial.

         11. Patients who have previously been randomised in this trial or in the respective twin
             trial (205.416 versus 205.417) or are currently participating in another trial.

         12. Patients with a known narrow-angle glaucoma.

        Note:

        As with other anticholinergic drugs, tiotropium should be used with caution in patients
        with prostatic hyperplasia or bladder neck obstruction.

        As with all predominantly renally excreted drugs, patients with moderate to severe renal
        impairment (known creatinine clearance of <= 50 mL/min) treated with tiotropium should be
        monitored closely.