Spiriva® Assessment of FEV1 (SAFE)

This study has been completed.
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
First received: January 9, 2006
Last updated: November 5, 2013
Last verified: November 2013
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 Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: Tiotropium (Spiriva®)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
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

Resource links provided by NLM:

Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • The primary efficacy endpoint was the change in trough FEV1 after 48 weeks of treatment. [ Time Frame: after 48 weeks of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The change from baseline FEV1 at interim visits [ Time Frame: at Week 2, 11, 30 and 48 ] [ Designated as safety issue: No ]
  • The change from baseline FVC [ Time Frame: at Week 2, 11, 30 and 48 ] [ Designated as safety issue: No ]
  • The change from baseline FEV6 (at selected sites) [ Time Frame: at Week 2, 11, 30 and 48 ] [ Designated as safety issue: No ]
  • Incidence, severity and duration of COPD exacerbations [ Time Frame: at Week 2, 11, 30, 48 and 50 ] [ Designated as safety issue: No ]
  • Incidence and duration of hospitalisations due to COPD exacerbations [ Time Frame: at Week 2, 11, 30, 48 and 50 ] [ Designated as safety issue: No ]
  • Use of rescue medication (day-time and night-time) during treatment period [ Time Frame: week 1 until week 48 ] [ Designated as safety issue: No ]
  • Number of short courses of steroids/antibiotics during treatment period [ Time Frame: week 1 until week 48 ] [ Designated as safety issue: No ]
  • Assessment of COPD symptoms [ Time Frame: at Week 2, 11, 30 and 48 ] [ Designated as safety issue: No ]
  • Physician's Global Evaluation [ Time Frame: baseline and week 48 ] [ Designated as safety issue: No ]
  • Quality of life questionnaire (SGRQ) [ Time Frame: at week 30 and 48 ] [ Designated as safety issue: No ]
  • Adverse events [ Time Frame: 27 months ] [ Designated as safety issue: No ]
  • Vital Signs [ Time Frame: 27 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 914
Study Start Date: January 2002
Estimated Study Completion Date: May 2004
Primary Completion Date: May 2004 (Final data collection date for primary outcome measure)
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


Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00277264

  Show 96 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Study Chair: Boehringer Ingelheim Study Coordinator B.I. Canada Ltd.
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00277264     History of Changes
Other Study ID Numbers: 205.259 
Study First Received: January 9, 2006
Last Updated: November 5, 2013
Health Authority: Canada: Therapeutic Products Directorate branch of Health Canada

Additional relevant MeSH terms:
Chronic Disease
Pulmonary Disease, Chronic Obstructive
Disease Attributes
Lung Diseases
Lung Diseases, Obstructive
Pathologic Processes
Respiratory Tract Diseases
Anti-Asthmatic Agents
Autonomic Agents
Bronchodilator Agents
Cholinergic Agents
Cholinergic Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 04, 2016