Spiriva® Assessment of FEV1 (SAFE)

Study Overview
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Brief Summary
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The objective of this trial is to evaluate whether the effect of one year (48 weeks) treatment with inhaled tiotropium bromide (Spiriva® - 18 µg once daily) on the change in trough FEV1, compared to placebo in patients with COPD, is affected by smoking status.

Detailed Description
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This was a multi-centre, randomised, double-blind, placebo-controlled study. The duration of subject participation was 48 weeks. There was an initial screening period of up to 2 weeks. The first screening visit consisted of medical history, clinical assessment, safety laboratory assessments and complete pulmonary function testing. The screening period was followed by a randomised treatment period where patients received tiotropium (Spiriva) or placebo in a ratio of 2:1. During the treatment period there were a total of 5 clinic visits (including randomisation and EOT visit). Each visit included lung function measurements and clinical assessments (SQRQ, COPD Symptom scores, physician's global assessment, COPD exacerbations/hospitalisations, vital signs and rescue medication use) in addition to adverse event reporting. The final visit consisted of a telephone contact 2 weeks after the patient completed their trial medication. Study Hypothesis: The primary purpose of this trial was to evaluate whether the effect of inhaled tiotropium (Spiriva®) on the change in trough FEV1, compared to placebo, was affected by smoking status. The primary endpoint was defined as the change in trough FEV1 after 48 weeks of treatment. The primary analysis was performed in a sequential fashion; firstly, the analysis was performed for all patients and if a positive signal was seen in this group, the analysis was then performed for both the smoking and ex-smoking groups separately. Patients were defined as smokers or ex-smokers at the screening visit. Comparison(s): Tiotropium (Spiriva®) vs placebo

Official Title
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Spiriva® Assessment of FEV1 (SAFE). The Effect of Inhaled Tiotropium Bromide (18 Mcg Once Daily) on the Change in FEV1 During Long-term Treatment in Patients With COPD. A One-year Parallel Group, Double-blind, Randomised, Placebo-controlled Study

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Tiotropium (Spiriva®)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of COPD Stable airway obstruction FEV1 < or equal to 65% of predicted Male or female Age > or equal to 40 years > or equal to 10 pack year smoking history History of exacerbations in the past year Able to be trained in the proper use of the HandiHaler® Exclusion Criteria: History of asthma Allergic rhinitis or atopy Unstable use (6 weeks) of OCS (or > 10 mg daily use) History of life threatening bronchial obstruction, cystic fibrosis or bronchiectasis Patients who had started or stopped an exercise rehabilitation program in the past twelve months Thoracotomy with pulmonary resection or lobectomy (LVRS) Active tuberculosis Use of beta-blockers Pregnant, nursing women and women of childbearing potential not using a medically approved means of contraception 6 months or less history of myocardial infarction Intolerance to anticholinergic containing products, and/or to lactose or any other components of the inhalation capsule delivery system History of unstable arrhythmia with a life threatening event or change of related therapy during the past year History of cancer, other than treated basal cell carcinoma, within the last 12 months Clinically relevant abnormal baseline haematology, blood chemistry or urinalysis Patients with narrow angle glaucoma Patients with symptomatic benign prostatic hypertrophy Patients with bladder neck obstruction Patients that planned to be out of the country for 8 weeks or more

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Tiotropium (Spiriva®)|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary efficacy endpoint was the change in trough FEV1 after 48 weeks of treatment. |  | after 48 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change from baseline FEV1 at interim visits |  | at Week 2, 11, 30 and 48 | 
| The change from baseline FVC |  | at Week 2, 11, 30 and 48 | 
| The change from baseline FEV6 (at selected sites) |  | at Week 2, 11, 30 and 48 | 
| Incidence, severity and duration of COPD exacerbations |  | at Week 2, 11, 30, 48 and 50 | 
| Incidence and duration of hospitalisations due to COPD exacerbations |  | at Week 2, 11, 30, 48 and 50 | 
| Use of rescue medication (day-time and night-time) during treatment period |  | week 1 until week 48 | 
| Number of short courses of steroids/antibiotics during treatment period |  | week 1 until week 48 | 
| Assessment of COPD symptoms |  | at Week 2, 11, 30 and 48 | 
| Physician's Global Evaluation |  | baseline and week 48 | 
| Quality of life questionnaire (SGRQ) |  | at week 30 and 48 | 
| Adverse events |  | 27 months | 
| Vital Signs |  | 27 months |