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Spiriva® Assessment of FEV1 (SAFE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00277264
Recruitment Status : Completed
First Posted : January 16, 2006
Last Update Posted : November 6, 2013
Information provided by:
Boehringer Ingelheim

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Pulmonary Disease, Chronic Obstructive Drug: Tiotropium (Spiriva®) Phase 3

Detailed Description:

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.


Tiotropium (Spiriva®) vs placebo

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Study Type : Interventional  (Clinical Trial)
Enrollment : 914 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Official Title: 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
Study Start Date : January 2002
Actual Primary Completion Date : May 2004
Study Completion Date : May 2004

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. The primary efficacy endpoint was the change in trough FEV1 after 48 weeks of treatment. [ Time Frame: after 48 weeks of treatment ]

Secondary Outcome Measures :
  1. The change from baseline FEV1 at interim visits [ Time Frame: at Week 2, 11, 30 and 48 ]
  2. The change from baseline FVC [ Time Frame: at Week 2, 11, 30 and 48 ]
  3. The change from baseline FEV6 (at selected sites) [ Time Frame: at Week 2, 11, 30 and 48 ]
  4. Incidence, severity and duration of COPD exacerbations [ Time Frame: at Week 2, 11, 30, 48 and 50 ]
  5. Incidence and duration of hospitalisations due to COPD exacerbations [ Time Frame: at Week 2, 11, 30, 48 and 50 ]
  6. Use of rescue medication (day-time and night-time) during treatment period [ Time Frame: week 1 until week 48 ]
  7. Number of short courses of steroids/antibiotics during treatment period [ Time Frame: week 1 until week 48 ]
  8. Assessment of COPD symptoms [ Time Frame: at Week 2, 11, 30 and 48 ]
  9. Physician's Global Evaluation [ Time Frame: baseline and week 48 ]
  10. Quality of life questionnaire (SGRQ) [ Time Frame: at week 30 and 48 ]
  11. Adverse events [ Time Frame: 27 months ]
  12. Vital Signs [ Time Frame: 27 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00277264

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Sponsors and Collaborators
Boehringer Ingelheim
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Study Chair: Boehringer Ingelheim Study Coordinator B.I. Canada Ltd.
Layout table for additonal information Identifier: NCT00277264    
Other Study ID Numbers: 205.259
First Posted: January 16, 2006    Key Record Dates
Last Update Posted: November 6, 2013
Last Verified: November 2013
Additional relevant MeSH terms:
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Pulmonary Disease, Chronic Obstructive
Lung Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Tiotropium Bromide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action