Clinical trial NCT00277264: Spiriva® Assessment of FEV1 (SAFE)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2006-01-16
Enrollment: 914
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Comparison(s):

Tiotropium (Spiriva®) vs placebo

Eligibility criteria: 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

Primary outcomes:
measure: The primary efficacy endpoint was the change in trough FEV1 after 48 weeks of treatment.
timeFrame: after 48 weeks of treatment
Secondary outcomes:
measure: The change from baseline FEV1 at interim visits
timeFrame: at Week 2, 11, 30 and 48
measure: The change from baseline FVC
timeFrame: at Week 2, 11, 30 and 48
measure: The change from baseline FEV6 (at selected sites)
timeFrame: at Week 2, 11, 30 and 48
measure: Incidence, severity and duration of COPD exacerbations
timeFrame: at Week 2, 11, 30, 48 and 50
measure: Incidence and duration of hospitalisations due to COPD exacerbations
timeFrame: at Week 2, 11, 30, 48 and 50
measure: Use of rescue medication (day-time and night-time) during treatment period
timeFrame: week 1 until week 48
measure: Number of short courses of steroids/antibiotics during treatment period
timeFrame: week 1 until week 48
measure: Assessment of COPD symptoms
timeFrame: at Week 2, 11, 30 and 48
measure: Physician's Global Evaluation
timeFrame: baseline and week 48
measure: Quality of life questionnaire (SGRQ)
timeFrame: at week 30 and 48
measure: Adverse events
timeFrame: 27 months
measure: Vital Signs
timeFrame: 27 months
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Respiratory Research, Room 1742
state: Alberta
city: Calgary
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Alberta
city: Calgary
country: Canada
facility: 4A-185, 7007-14 Street SW
state: Alberta
city: Edmonton
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Alberta
city: Lethbridge
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Alberta
city: Medicine Hat
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Alberta
city: Spruce Grove
country: Canada
facility: 301-131 First Ave.
state: Alberta
city: Wetaskiwin
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Alberta
city: Abbotsford
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: British Columbia
city: Chilliwack
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: British Columbia
city: Kelowna
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: British Columbia
city: Maple Ridge
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: British Columbia
city: New Westminster
country: Canada
facility: 220 Royal Avenue
state: British Columbia
city: Penticton
country: Canada
facility: Penticton Regional Hospital
state: British Columbia
city: Surrey
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: British Columbia
city: Vancouver
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: British Columbia
city: Vancouver
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: British Columbia
city: Vancouver
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: British Columbia
city: Victoria
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: British Columbia
city: Steinbach
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Manitoba
city: Winnipeg
country: Canada
facility: 1095 Concordia Avenue
state: Manitoba
city: Saint John
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: New Brunswick
city: Mount Pearl
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Newfoundland and Labrador
city: St. John's
country: Canada
facility: 262 Newfoundland Drive
state: Newfoundland and Labrador
city: St. John's
country: Canada
facility: 300 Prince Philip Drive
state: Newfoundland and Labrador
city: New Glasgow
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Nova Scotia
city: Sydney
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Nova Scotia
city: Ajax
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Corunna
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Courtice
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Grimsby
country: Canada
facility: 169 Main Street East
state: Ontario
city: Hamilton
country: Canada
facility: 237 Barton Street East
state: Ontario
city: Hamilton
country: Canada
facility: HGH McMaster Clinic
state: Ontario
city: Hamilton
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Hamilton
country: Canada
facility: 50 Charlton Avenue East
state: Ontario
city: Hamilton
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Kingston
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Kitchener
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: London
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: London
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: London
country: Canada
facility: Haemolology Division
state: Ontario
city: London
country: Canada
facility: St Joseph's Healthcare
state: Ontario
city: London
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Markham
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Mississauga
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Mississauga
country: Canada
facility: 300-2338 Hurontario Street
state: Ontario
city: Mississauga
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Niagara Falls
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: North York
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: North York
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital - General Campus
state: Ontario
city: Ottawa
country: Canada
facility: 1053 Carling Avenue
state: Ontario
city: Ottawa
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Peterborough
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Richmond Hill
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Sarnia
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Scarborough
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Thunder Bay
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 825 Coxwell Avenue
state: Ontario
city: Toronto
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 600 Sherbourne Street, Suite 402
state: Ontario
city: Toronto
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Toronto
country: Canada
facility: 76 Grenville Street
state: Ontario
city: Trenton
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Windsor
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: York
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Boucherville
country: Canada
facility: 91 Thomas-Chapais
state: Quebec
city: Chicoutimi
country: Canada
facility: 305 rue Saint-Vallier
state: Quebec
city: Gatineau
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Quebec
city: Granby
country: Canada
facility: 4 rue Robinson
state: Quebec
city: Greenfield Park
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Quebec
city: La Malbaie
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Quebec
city: Laval
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: 2180 rue Fleury E
state: Quebec
city: Montreal
country: Canada
facility: UHRESS, Pavillon L-C Simard, 10th Floor, Z10904
state: Quebec
city: Montreal
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: Hop du Sacre-Coeur de Montreal
state: Quebec
city: Montreal
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Quebec
city: Pointe Claire
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Quebec
city: Saint Jerome
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Quebec
city: Sherbrooke
country: Canada
facility: 3001 12e ave Nord
state: Quebec
city: St-Jean Richelieu
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Quebec
city: Ste-Foy
country: Canada
facility: Hopital Laval
state: Quebec
city: Saskatoon
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Saskatchewan
city: Quebec
country: Canada
facility: 1401-18 Rue
Study officials:
affiliation: B.I. Canada Ltd.
name: Boehringer Ingelheim Study Coordinator
role: STUDY_CHAIR
References: