Clinical trial NCT00239408: Spiriva (Tiotropium Bromide) Assessment of FEV1 - (SAFE-Portugal).
Official title: Spiriva Assessment of FEV1 - (SAFE-Portugal). The Effect of Inhaled Tiotropium Bromide (18 Mcg Once Daily) on the Change in FEV1 During Treatment in Patients With COPD. A Three-month Parallel Group, Double-blind, Randomised, Placebo-controlled Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2005-10-17
Enrollment: 311
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: Evaluate whether the effect of inhaled tiotropium bromide on the change in trough forced expiratory volume (FEV1), compared to placebo in patients with chronic obstructive pulmonary disease (COPD), is affected by smoking status.

Detailed description: Evaluate whether the effect of inhaled tiotropium bromide on the change in trough FEV1 from baseline to week 12 compared to placebo in patients with COPD is affected by smoking status. Secondary objectives include FEV1 at interim visit and FVC at on-treatment visits, use of rescue medication, COPD symptom scores, Physicians Global Evaluation and EQ-5D scores.

Study Hypothesis:

The primary objective of the study is to show superiority of tiotropium against placebo with respect to trough FEV1 at 12 weeks. Then the 5% two-sided hypotheses test is:

H0: Mean trough FEV1 at 12 weeks in tiotropium = Mean trough FEV1 at 12 weeks in placebo H1: Mean trough FEV1 at 12 weeks in tiotropium unequal Mean trough FEV1 at 12 weeks in placebo If the null hypothesis is rejected in favour of the alternative hypothesis (H1) based on all patients, the same hypotheses will be tested in both sub-populations of current and ex-smokers respectively.

Comparison(s):

Tiotropium bromide - 18 mcg capsule inhaled via the HandiHaler vs Placebo powder capsules for oral inhalation, via the HandiHaler.

Eligibility criteria: Main Inclusion criteria: 1.Diagnosis of chronic obstructive pulmonary disease. 2.Patient is male or female, age \<=than 40 years. 3. Patient has a smoking history of \<=10 pack-year.4.Patient is able to be trained in the proper use of HandiHaler 5.Patient is able to be trained to perform technically satisfactory spirometry and must be able to maintain records during the study period as required by the protocol. 6.Patient must be willing and able to sign informed consent prior to participation in the study i.e. prior to washout of their usual pulmonary medications.

Main exclusion criteria 1.History of asthma, allergic rhinitis or atopy. 2. A lower respiratory tract infection or any COPD exacerbation in the past 4 weeks prior to Visit 1 or during the two week Screening Period 3.History of life threatening bronchial obstruction, cystic fibrosis or bronchiectasis 4. Oral corticosteroid medication if initiated or modified within the last 6 weeks prior to Visit 1 or if daily dose \> 10 mg prednisone or 20 mg or more every other day (or equivalent). 5.Patients who have started or stopped an exercise rehabilitation program within 4 weeks of visit 6.Patients who regularly use daytime oxygen therapy for more than one hour per day and who, in the investigator's opinion, will be unable to abstain from the use of oxygen therapy during testing. 7. Patients who have undergone thoracotomy with pulmonary resection or lobectomy (lung volume reduction surgery). 8.Tuberculosis with indication for treatment. 9. Recent history (i.e. 6 months or less) of myocardial infarction.10. Patients with known moderate or severe renal insufficiency.11. Patients with symptomatic prostatic hypertrophy or bladder neck obstruction. 12.Patients with known narrow-angle glaucoma.13.History of unstable arrhythmia with a life threatening event or change of therapy during the past year.14. History of cancer, other than treated basal cell carcinoma, within the last 5 years 15.Intolerance to anticholinergic containing products, and/or to lactose or any other components of the inhalation capsule delivery system.16.Patients who are being treated with beta-blockers including eye drops.17.Patients who are being treated with antihistamines (H1 receptor antagonists), for asthma or excluded allergic conditions (See Exclusion Criteria No.2).18.Patients who are being treated with monoamine oxidase inhibitors or tricyclic antidepressants.19. Patients who are being treated with oral beta-adrenergics.20. Patients who have taken cromolyn sodium or nedocromil sodium within 1 month of Visit 1.21.Patients who have taken antileukotrienes or leukotriene receptor antagonists within 1 month of Visit 1. 22.Concomitant or recent (within the last month or 6 half lives, whichever is greater) use of investigational drugs prior to the screening visit (Visit 1). 23. Significant alcohol or drug abuse within the past 12 months. 24. Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception.24. Previous participation in this study (i.e. randomized).26. Patients who have taken commercially available Spiriva. 27.History of any clinically significant disease, defined as a disease which in the opinion of the investigator may the patient at risk because of participation in the study OR a disease which may influence the results of the study OR the patient's ability to participate in the study.

Primary outcomes:
measure: Change in trough FEV1 after 12 weeks of treatment.
timeFrame: week 12
Secondary outcomes:
measure: Trough FEV1 at interim visit
timeFrame: week 6
measure: Change in FVC at weeks 6 and 12
timeFrame: week 6, week 12
measure: Use of rescue medication (daytime and night-time)
timeFrame: 12 weeks
measure: Assessment of COPD symptoms
timeFrame: week 0, week 6, week 12
measure: The Physician's Global Evaluation at Visits 2 and 4
timeFrame: week 0, week 12
measure: Quality of life questionnaire (EQ-5D) at Visits 2 and 4
timeFrame: week 0, week 12
measure: Pulse Rate
timeFrame: 12 weeks
measure: Blood Pressure
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Almada
country: Portugal
facility: Hospital Garcia de Orta
city: Amadora
country: Portugal
facility: Hospital Fernando Fonseca
city: Angra do Heroismo - Açores
country: Portugal
facility: Hospital Santo Espírito de Angra do Heroismo
city: Aveiro
country: Portugal
facility: Hospital Infante D. Pedro
city: Barreiro
country: Portugal
facility: Unidade Funcional de Infecciologia
city: Braga
country: Portugal
facility: Hospital de S. Marcos
city: Coimbra
country: Portugal
facility: Hospitais da Universidade de Coimbra
city: Coimbra
country: Portugal
facility: Centro Hospitalar de Coimbra
city: Covilhã
country: Portugal
facility: Centro Hospitalar da Cova da Beira
city: Faro
country: Portugal
facility: Hospital Distrital de Faro
city: Figueira da Foz
country: Portugal
facility: Hospital Distrital da Figueira da Foz
city: Funchal
country: Portugal
facility: Centro Hospitalar do Funchal
city: Guarda
country: Portugal
facility: Hospital de Sousa Martins
city: Guimarães
country: Portugal
facility: Hospital Senhora da Oliveira
city: Lisboa
country: Portugal
facility: Hospital Particular de Lisboa
city: Lisboa
country: Portugal
facility: Instituto Português de Oncologia Francisco Gentil
city: Lisboa
country: Portugal
facility: Hospital de Santa Marta - HCL
city: Lisboa
country: Portugal
facility: Hospital Pulido Valente
city: Lisbon
country: Portugal
facility: Hospital Egas Moniz
city: Lisbon
country: Portugal
facility: Hospital Santa Maria
city: Matosinhos
country: Portugal
facility: Unidade Local de Saúde de Matosinhos
city: Ponta Delgada - Açores
country: Portugal
facility: Hospital Divino Espírito Santo
city: Portimão
country: Portugal
facility: Hospital Barlavento Algarvio
city: Porto
country: Portugal
facility: Hospital Geral de Santo António
city: Porto
country: Portugal
facility: Hospital de São João
city: Porto
country: Portugal
facility: Hospital Joaquim Urbano
city: Santarém
country: Portugal
facility: Hospital Distrital de Santarém
city: Setúbal
country: Portugal
facility: Hospital de S. Bernardo
city: Sta. Maria da Feira
country: Portugal
facility: Hospital de S. Sebastião
city: Torres Novas
country: Portugal
facility: Hospital Rainha Santa Isabel
city: V.N.Gaia
country: Portugal
facility: Centro Hospitalar de V. N. de Gaia
city: Viseu
country: Portugal
facility: Hospital de S. Teotónio
city: Évora
country: Portugal
facility: Hospital Espírito Santo
Study officials:
affiliation: B.I. Portugal Lda
name: Boehringer Ingelheim Study Coordinator
role: STUDY_CHAIR
References: