Clinical trial NCT00168831: Tiotropium / Respimat One-Year Study
Official title: A Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Efficacy and Safety Comparison of One-Year Treatment of Two Doses (5mg and 10mg) of Tiotropium Inhalation Solution Delivered by the Respimat Device in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2005-09-15
Enrollment: 1007
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: To evaluate the long term effects of treatment with two doses of Tiotropium delivered by the Respimat inhaler in patients with COPD.


Eligibility criteria: Criteria

* Patients with stable moderate to severe COPD and a smoking history of at least 10 pack years were eligible for inclusion in the study. Patients with significant diseases other than COPD were excluded as were patients with a recent history of myocardial infarction, history of malignancy, unstable or life-threatening cardiac arrhythmia, narrow-angle glaucoma, asthma or other allergic conditions. Patients treated with cromolyn, nedocromil, oral beta-adrenergics or unstable doses of oral corticosteroids were ineligible for inclusion in the study as were patients who had received previous treatment with tiotropium.

Primary outcomes:
measure: Change From Baseline in Trough FEV1 After 48 Weeks
timeFrame: 10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication
measure: Saint George's Respiratory Questionnaire (SGRQ) Total Score, Full Analysis Set - Saint George's Respiratory Questionnaire (FAS-QOL)
timeFrame: Week 48
measure: TDI Focal Score, Full Analysis Set - Transitional Dyspnoea Index (FAS-TDI) (Combined Studies)
timeFrame: Week 48
measure: COPD Exacerbation Rate, Safety Set (SS) (Combined Studies)
timeFrame: 48 weeks
Secondary outcomes:
measure: Change From Baseline in Heart Rate
timeFrame: Baseline to Week 40 pre-dose
measure: Change From Baseline in PR Interval
timeFrame: Baseline to Week 40 pre-dose
measure: Change From Baseline in QRS Interval
timeFrame: Baseline to Week 40 pre-dose
measure: Change From Baseline in QT Interval
timeFrame: Baseline to Week 40 pre-dose
measure: Change From Baseline in QT Interval (Bazett)
timeFrame: Baseline to Week 40 pre-dose
measure: Change From Baseline in QT Interval (Fridericia)
timeFrame: Baseline to Week 40 pre-dose
measure: Change From Baseline in Heart Rate
timeFrame: Baseline to Week 40
measure: Change From Baseline in Supraventricular Premature Beat (SVPB) Total
timeFrame: Baseline to Week 40
measure: Change From Baseline in SVPB Run Events
timeFrame: Baseline to Week 40
measure: Change From Baseline in SVPB Pairs
timeFrame: Baseline to Week 40
measure: Change From Baseline in Ventricular Premature Beat (VPB) Total
timeFrame: Baseline to Week 40
measure: Change From Baseline in Ventricular Premature Beat (VPB) Run Events
timeFrame: Baseline to Week 40
measure: Change From Baseline in VPB Pairs
timeFrame: Baseline to Week 40
measure: Change From Baseline in Haematocrit, Packed Cell Volume (PCV)
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Haemoglobin
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Red Blood Cell Count
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in White Blood Cell Count
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Platelets
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Neutrophils
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Eosinophils
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Basophils
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Lymphocytes
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Monocytes
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Neutrophils (Absolute)
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Eosinophils (Absolute)
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Basophils (Absolute)
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Lymphocytes (Absolute)
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Monocytes (Absolute)
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Calcium
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Phosphate
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Aspartate Transaminase/Glutamic-oxaloacetic Transaminase (AST/GOT), Serum Glutamic-oxaloacetic Transaminase (SGOT)
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Alanine Transaminase/Glutamic Pyruvate Transaminase (ALT/GPT), Serum Glutamate Pyruvate Transaminase (SGPT)
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Alkaline Phosphatase
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Lactic Dehyrogenase (LDH)
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Glucose
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Urea
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Blood Urea Nitrogen
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Creatinine
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Bilirubin, Total
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Uric Acid
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Protein, Total
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Albumin
timeFrame: Baseline to Week 48 or at premature discontinuation if before Week 48
measure: Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks
timeFrame: 10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication
measure: Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks
timeFrame: 10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication
measure: Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks
timeFrame: 10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication
measure: Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks
timeFrame: 10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication
measure: Weekly Mean Morning Pre-dose PEFRs
timeFrame: Weeks 2, 8, 16, 24, 32, 40, 48
measure: Weekly Mean Morning Evening PEFRs
timeFrame: Weeks 2, 8, 16, 24, 32, 40, 48
measure: Weekly Mean Number of Puffs of Rescue Medication Per Day
timeFrame: Weeks 2, 8, 16, 24, 32, 40, 48
measure: Mahler TDI Scores
timeFrame: Week 48
measure: Saint George's Respiratory Questionnaire (SGRQ) Scores
timeFrame: Week 48
measure: COPD Symptoms Scores
timeFrame: Week 48
measure: PGE Scores
timeFrame: Week 48
measure: PGR Scores
timeFrame: Week 48
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Alabama
city: La Jolla
country: United States
facility: Boehringer Ingelheim Investigational Site
state: California
city: Long Beach
country: United States
facility: Boehringer Ingelheim Investigational Site
state: California
city: San Luis Obispo
country: United States
facility: Boehringer Ingelheim Investigational Site
state: California
city: Gainesville
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Florida
city: Hallandale
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Florida
city: Hines
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Illinois
city: Chesterfield
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Missouri
city: Bay Shore
country: United States
facility: Boehringer Ingelheim Investigational Site
state: New York
city: Charleston
country: United States
facility: Boehringer Ingelheim Investigational Site
state: South Carolina
city: Houston
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Texas
city: Richmond
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Virginia
city: Garran
country: Australia
facility: Boehringer Ingelheim Investigational Site
state: Australian Capital Territory
city: Adelaide
country: Australia
facility: Boehringer Ingelheim Investigational Site
state: South Australia
city: Nedlands
country: Australia
facility: Boehringer Ingelheim Investigational Site
state: Western Australia
city: Innsbruck
country: Austria
facility: Boehringer Ingelheim Investigational Site
city: Mittersill
country: Austria
facility: Boehringer Ingelheim Investigational Site
city: Schwechat
country: Austria
facility: Boehringer Ingelheim Investigational Site
city: Wels
country: Austria
facility: Boehringer Ingelheim Investigational Site
city: Wien
country: Austria
facility: Baumgartner Hohe Otto Wagner Spital Wien
city: Wien
country: Austria
facility: Boehringer Ingelheim Investigational Site
city: Winnipeg
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Manitoba
city: Hamilton
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Quebec
city: Sherbrooke
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Quebec
city: Espoo
country: Finland
facility: Boehringer Ingelheim Investigational Site
city: Helsinki
country: Finland
facility: Boehringer Ingelheim Investigational Site
city: Lahti
country: Finland
facility: Boehringer Ingelheim Investigational Site
city: Lappeenranta
country: Finland
facility: Boehringer Ingelheim Investigational Site
city: Lohja
country: Finland
facility: Boehringer Ingelheim Investigational Site
city: Amboise cedex
country: France
facility: Boehringer Ingelheim Investigational Site
city: Chauny
country: France
facility: Boehringer Ingelheim Investigational Site
city: Marseille cedex 06
country: France
facility: Boehringer Ingelheim Investigational Site
city: Metz cedex 01
country: France
facility: Boehringer Ingelheim Investigational Site
city: Montpellier
country: France
facility: Boehringer Ingelheim Investigational Site
city: Nantes
country: France
facility: Boehringer Ingelheim Investigational Site
city: Alexandroupolis
country: Greece
facility: Boehringer Ingelheim Investigational Site
city: Athens
country: Greece
facility: Boehringer Ingelheim Investigational Site
city: Mournies-Chania
country: Greece
facility: Boehringer Ingelheim Investigational Site
city: Trikala
country: Greece
facility: Boehringer Ingelheim Investigational Site
city: Dublin 4
country: Ireland
facility: Boehringer Ingelheim Investigational Site
city: Dublin 7
country: Ireland
facility: Boehringer Ingelheim Investigational Site
city: Dublin
country: Ireland
facility: Boehringer Ingelheim Investigational Site
city: Bologna
country: Italy
facility: Boehringer Ingelheim Investigational Site
city: Bussolengo (vr)
country: Italy
facility: Boehringer Ingelheim Investigational Site
city: Cava dei tirreni (SA)
country: Italy
facility: Boehringer Ingelheim Investigational Site
city: Crema (CR)
country: Italy
facility: Boehringer Ingelheim Investigational Site
city: Genova
country: Italy
facility: Boehringer Ingelheim Investigational Site
city: Milano
country: Italy
facility: Boehringer Ingelheim Investigational Site
city: Pistoia
country: Italy
facility: Boehringer Ingelheim Investigational Site
city: Roma
country: Italy
facility: Boehringer Ingelheim Investigational Site
city: Salerno
country: Italy
facility: Boehringer Ingelheim Investigational Site
city: Sesto San Giovanni (Milano)
country: Italy
facility: Boehringer Ingelheim Investigational Site
city: Arnhem
country: Netherlands
facility: Boehringer Ingelheim Investigational Site
city: Eindhoven
country: Netherlands
facility: Boehringer Ingelheim Investigational Site
city: Heerenveen
country: Netherlands
facility: Boehringer Ingelheim Investigational Site
city: Hoorn
country: Netherlands
facility: Boehringer Ingelheim Investigational Site
city: Leeuwarden
country: Netherlands
facility: Boehringer Ingelheim Investigational Site
city: Rotterdam
country: Netherlands
facility: Boehringer Ingelheim Investigational Site
city: Auckland
country: New Zealand
facility: Boehringer Ingelheim Investigational Site
city: Hamilton
country: New Zealand
facility: Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: Boehringer Ingelheim Investigational Site
city: Bellville
country: South Africa
facility: Boehringer Ingelheim Investigational Site
city: Cape Town
country: South Africa
facility: Boehringer Ingelheim Investigational Site
city: George
country: South Africa
facility: Boehringer Ingelheim Investigational Site
city: Johannesburg
country: South Africa
facility: Boehringer Ingelheim Investigational Site
city: Vanderbijlpark
country: South Africa
facility: Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: Boehringer Ingelheim Investigational Site
city: Centelles
country: Spain
facility: Boehringer Ingelheim Investigational Site
city: Murcia
country: Spain
facility: Boehringer Ingelheim Investigational Site
city: Sant Boi de Llobregat (Barcelona)
country: Spain
facility: Boehringer Ingelheim Investigational Site
city: Babbacombe
country: United Kingdom
facility: Boehringer Ingelheim Investigational Site
city: Cottingham
country: United Kingdom
facility: Boehringer Ingelheim Investigational Site
city: Isleworth
country: United Kingdom
facility: Boehringer Ingelheim Investigational Site
city: Manchester
country: United Kingdom
facility: Boehringer Ingelheim Investigational Site
city: Plymouth
country: United Kingdom
facility: Boehringer Ingelheim Investigational Site
city: Sunderland
country: United Kingdom
facility: Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim Study Coordinator
role: STUDY_CHAIR
References:
citation: Singh D, Wedzicha JA, Siddiqui S, de la Hoz A, Xue W, Magnussen H, Miravitlles M, Chalmers JD, Calverley PMA. Blood eosinophils as a biomarker of future COPD exacerbation risk: pooled data from 11 clinical trials. Respir Res. 2020 Sep 17;21(1):240. doi: 10.1186/s12931-020-01482-1.
citation: Hohlfeld JM, Furtwaengler A, Konen-Bergmann M, Wallenstein G, Walter B, Bateman ED. Cardiac safety of tiotropium in patients with COPD: a combined analysis of Holter-ECG data from four randomised clinical trials. Int J Clin Pract. 2015 Jan;69(1):72-80. doi: 10.1111/ijcp.12596. Epub 2014 Dec 11.
citation: Hodder R, Pavia D, Lee A, Bateman E. Lack of paradoxical bronchoconstriction after administration of tiotropium via Respimat(R) Soft Mist Inhaler in COPD. Int J Chron Obstruct Pulmon Dis. 2011;6:245-51. doi: 10.2147/COPD.S16094. Epub 2011 Apr 26.