Tiotropium / Respimat One-Year Study

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)

To evaluate the long term effects of treatment with two doses of Tiotropium delivered by the Respimat inhaler in patients with COPD.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Other: Placebo; Drug: Tiotropium Inhalation Solution

• Study Type: Interventional
• Enrollment (Actual): 1007
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia
      • Boehringer Ingelheim Investigational Site
  • South Australia
    • Adelaide, South Australia, Australia
      • Boehringer Ingelheim Investigational Site
  • Western Australia
    • Nedlands, Western Australia, Australia
      • Boehringer Ingelheim Investigational Site
• Austria
  • Innsbruck, Austria
    • Boehringer Ingelheim Investigational Site
  • Mittersill, Austria
    • Boehringer Ingelheim Investigational Site
  • Schwechat, Austria
    • Boehringer Ingelheim Investigational Site
  • Wels, Austria
    • Boehringer Ingelheim Investigational Site
  • Wien, Austria
    • Boehringer Ingelheim Investigational Site
  • Wien, Austria
    • Baumgartner Hohe Otto Wagner Spital Wien
• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada
      • Boehringer Ingelheim Investigational Site
  • Ontario
    • Hamilton, Ontario, Canada
      • Boehringer Ingelheim Investigational Site
    • Toronto, Ontario, Canada
      • Boehringer Ingelheim Investigational Site
  • Quebec
    • Montreal, Quebec, Canada
      • Boehringer Ingelheim Investigational Site
    • Sherbrooke, Quebec, Canada
      • Boehringer Ingelheim Investigational Site
• Finland
  • Espoo, Finland
    • Boehringer Ingelheim Investigational Site
  • Helsinki, Finland
    • Boehringer Ingelheim Investigational Site
  • Lahti, Finland
    • Boehringer Ingelheim Investigational Site
  • Lappeenranta, Finland
    • Boehringer Ingelheim Investigational Site
  • Lohja, Finland
    • Boehringer Ingelheim Investigational Site
• France
  • Amboise cedex, France
    • Boehringer Ingelheim Investigational Site
  • Chauny, France
    • Boehringer Ingelheim Investigational Site
  • Marseille cedex 06, France
    • Boehringer Ingelheim Investigational Site
  • Metz cedex 01, France
    • Boehringer Ingelheim Investigational Site
  • Montpellier, France
    • Boehringer Ingelheim Investigational Site
  • Nantes, France
    • Boehringer Ingelheim Investigational Site
• Greece
  • Alexandroupolis, Greece
    • Boehringer Ingelheim Investigational Site
  • Athens, Greece
    • Boehringer Ingelheim Investigational Site
  • Mournies-Chania, Greece
    • Boehringer Ingelheim Investigational Site
  • Trikala, Greece
    • Boehringer Ingelheim Investigational Site
• Ireland
  • Dublin, Ireland
    • Boehringer Ingelheim Investigational Site
  • Dublin 4, Ireland
    • Boehringer Ingelheim Investigational Site
  • Dublin 7, Ireland
    • Boehringer Ingelheim Investigational Site
• Italy
  • Bologna, Italy
    • Boehringer Ingelheim Investigational Site
  • Bussolengo (vr), Italy
    • Boehringer Ingelheim Investigational Site
  • Cava dei tirreni (SA), Italy
    • Boehringer Ingelheim Investigational Site
  • Crema (CR), Italy
    • Boehringer Ingelheim Investigational Site
  • Genova, Italy
    • Boehringer Ingelheim Investigational Site
  • Milano, Italy
    • Boehringer Ingelheim Investigational Site
  • Pistoia, Italy
    • Boehringer Ingelheim Investigational Site
  • Roma, Italy
    • Boehringer Ingelheim Investigational Site
  • Salerno, Italy
    • Boehringer Ingelheim Investigational Site
  • Sesto San Giovanni (Milano), Italy
    • Boehringer Ingelheim Investigational Site
• Netherlands
  • Arnhem, Netherlands
    • Boehringer Ingelheim Investigational Site
  • Eindhoven, Netherlands
    • Boehringer Ingelheim Investigational Site
  • Heerenveen, Netherlands
    • Boehringer Ingelheim Investigational Site
  • Hoorn, Netherlands
    • Boehringer Ingelheim Investigational Site
  • Leeuwarden, Netherlands
    • Boehringer Ingelheim Investigational Site
  • Rotterdam, Netherlands
    • Boehringer Ingelheim Investigational Site
• New Zealand
  • Auckland, New Zealand
    • Boehringer Ingelheim Investigational Site
  • Hamilton, New Zealand
    • Boehringer Ingelheim Investigational Site
• Russian Federation
  • St. Petersburg, Russian Federation
    • Boehringer Ingelheim Investigational Site
• South Africa
  • Bellville, South Africa
    • Boehringer Ingelheim Investigational Site
  • Cape Town, South Africa
    • Boehringer Ingelheim Investigational Site
  • George, South Africa
    • Boehringer Ingelheim Investigational Site
  • Johannesburg, South Africa
    • Boehringer Ingelheim Investigational Site
  • Vanderbijlpark, South Africa
    • Boehringer Ingelheim Investigational Site
• Spain
  • Barcelona, Spain
    • Boehringer Ingelheim Investigational Site
  • Centelles, Spain
    • Boehringer Ingelheim Investigational Site
  • Murcia, Spain
    • Boehringer Ingelheim Investigational Site
  • Sant Boi de Llobregat (Barcelona), Spain
    • Boehringer Ingelheim Investigational Site
• United Kingdom
  • Babbacombe, United Kingdom
    • Boehringer Ingelheim Investigational Site
  • Cottingham, United Kingdom
    • Boehringer Ingelheim Investigational Site
  • Isleworth, United Kingdom
    • Boehringer Ingelheim Investigational Site
  • Manchester, United Kingdom
    • Boehringer Ingelheim Investigational Site
  • Plymouth, United Kingdom
    • Boehringer Ingelheim Investigational Site
  • Sunderland, United Kingdom
    • Boehringer Ingelheim Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States
      • Boehringer Ingelheim Investigational Site
  • California
    • La Jolla, California, United States
      • Boehringer Ingelheim Investigational Site
    • Long Beach, California, United States
      • Boehringer Ingelheim Investigational Site
    • San Luis Obispo, California, United States
      • Boehringer Ingelheim Investigational Site
  • Florida
    • Gainesville, Florida, United States
      • Boehringer Ingelheim Investigational Site
    • Hallandale, Florida, United States
      • Boehringer Ingelheim Investigational Site
  • Illinois
    • Hines, Illinois, United States
      • Boehringer Ingelheim Investigational Site
  • Missouri
    • Chesterfield, Missouri, United States
      • Boehringer Ingelheim Investigational Site
  • New York
    • Bay Shore, New York, United States
      • Boehringer Ingelheim Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States
      • Boehringer Ingelheim Investigational Site
  • Texas
    • Houston, Texas, United States
      • Boehringer Ingelheim Investigational Site
  • Virginia
    • Richmond, Virginia, United States
      • Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Placebo	Other: Placebo
Other: Tiotropium Respimat 5mcg (Tio R5)	Drug: Tiotropium Inhalation Solution
Other: Tiotropium Respimat 10mcg (Tio R10)	Drug: Tiotropium Inhalation Solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Trough FEV1 After 48 Weeks	Change From Baseline in Trough Forced Expiratory Volume in 1 second (FEV1) after 48 weeks	10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication
Saint George's Respiratory Questionnaire (SGRQ) Total Score, Full Analysis Set - Saint George's Respiratory Questionnaire (FAS-QOL)	Rating scale of 3 domains - symptoms, activities and impact (weighted). Worst score = 100, best score = 0	Week 48
TDI Focal Score, Full Analysis Set - Transitional Dyspnoea Index (FAS-TDI) (Combined Studies)	Rating scale of 3 components - change in functional impairment, change in magnitude of tasks, change in magnitude of efforts. Worst score = -9, best score = +9 For this endpoint data of twin studies NCT00168844 and NCT00168831 was combined.	Week 48
COPD Exacerbation Rate, Safety Set (SS) (Combined Studies)	Number of Chronic Obstructive Pulmonary Disease (COPD) exacerbations per patient year For this endpoint data of the twin studies NCT00168844 and NCT00168831 was combined.	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Heart Rate	Week 40 pre-dose - baseline	Baseline to Week 40 pre-dose
Change From Baseline in PR Interval		Baseline to Week 40 pre-dose
Change From Baseline in QRS Interval	Week 40 pre-dose - baseline	Baseline to Week 40 pre-dose
Change From Baseline in QT Interval	Week 40 pre-dose - baseline	Baseline to Week 40 pre-dose
Change From Baseline in QT Interval (Bazett)	Week 40 pre-dose - baseline	Baseline to Week 40 pre-dose
Change From Baseline in QT Interval (Fridericia)	Week 40 pre-dose - baseline	Baseline to Week 40 pre-dose
Change From Baseline in Heart Rate	Week 40 - baseline	Baseline to Week 40
Change From Baseline in Supraventricular Premature Beat (SVPB) Total	Week 40 - baseline	Baseline to Week 40
Change From Baseline in SVPB Run Events	Week 40 - baseline	Baseline to Week 40
Change From Baseline in SVPB Pairs	Week 40 - baseline	Baseline to Week 40
Change From Baseline in Ventricular Premature Beat (VPB) Total	Week 40 - baseline	Baseline to Week 40
Change From Baseline in Ventricular Premature Beat (VPB) Run Events	Week 40 - baseline	Baseline to Week 40
Change From Baseline in VPB Pairs	Week 40 - baseline	Baseline to Week 40
Change From Baseline in Haematocrit, Packed Cell Volume (PCV)		Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Haemoglobin	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Red Blood Cell Count	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in White Blood Cell Count	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Platelets	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Neutrophils	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Eosinophils	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Basophils	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Lymphocytes	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Monocytes	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Neutrophils (Absolute)	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Eosinophils (Absolute)	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Basophils (Absolute)	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Lymphocytes (Absolute)	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Monocytes (Absolute)	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Calcium	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Phosphate	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Aspartate Transaminase/Glutamic-oxaloacetic Transaminase (AST/GOT), Serum Glutamic-oxaloacetic Transaminase (SGOT)	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Alanine Transaminase/Glutamic Pyruvate Transaminase (ALT/GPT), Serum Glutamate Pyruvate Transaminase (SGPT)	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Alkaline Phosphatase	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Lactic Dehyrogenase (LDH)	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Glucose	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Urea	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Blood Urea Nitrogen	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Creatinine	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Bilirubin, Total	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Uric Acid	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Protein, Total	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Albumin	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48
Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks	Change From Baseline in Trough Forced Expiratory Volume in 1 second (FEV1) after 2, 8, 16, 24, 32 and 40 weeks. The means are adjusted for centre, smoking status at entry and baseline value.	10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication
Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks	Change From Baseline in Trough Forced vital capacity (FVC) after 2, 8, 16, 24, 32, 40 and 48 weeks. The means are adjusted for centre, smoking status at entry and baseline value.	10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication
Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks	FEV1 AUC0-3 represents the Area under Curve over the time interval from 0 to 3 hours after 2, 8, 16, 24, 32, 40 and 48 weeks. The means are adjusted for centre, smoking status at entry and baseline value.	10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication
Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks	FVC AUC0-3 represents the Area under Curve over the time interval from 0 to 3 hours after 2, 8, 16, 24, 32, 40 and 48 weeks. The means are adjusted for centre, smoking status at entry and baseline value.	10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication
Weekly Mean Morning Pre-dose PEFRs	Weekly mean morning pre-dose peak expiratory flow rates (PEFRs). The means are adjusted for centre, smoking status at entry, and baseline value.	Weeks 2, 8, 16, 24, 32, 40, 48
Weekly Mean Morning Evening PEFRs	Weekly mean evening peak expiratory flow rates (PEFRs). The means are adjusted for centre, smoking status at entry, and baseline value.	Weeks 2, 8, 16, 24, 32, 40, 48
Weekly Mean Number of Puffs of Rescue Medication Per Day	Weekly mean number of puffs of rescue medication used per day as required (PRN salbutamol). The means are adjusted for centre, smoking status at entry, and baseline value.	Weeks 2, 8, 16, 24, 32, 40, 48
Mahler TDI Scores	Mahler Transitional Dyspnoea Index (TDI) scores measured as change in functional impairment, change in magnitude of tasks and change in magnitude of efforts over the treatment period. The means are adjusted for centre, smoking status at entry and baseline value. Worst score = -3, best score = +3	Week 48
Saint George's Respiratory Questionnaire (SGRQ) Scores	Saint George's Respiratory Questionnaire (SGRQ) Scores impacts, activities and symptoms. Worst score = 100, best score = 0. The means are adjusted for centre, smoking status at entry and baseline value.	Week 48
COPD Symptoms Scores	COPD symptoms Scores - wheezing, shortness of breath, coughing and tightness of chest over the treatment period. Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe The means are adjusted for centre, smoking status at entry and baseline value.	Week 48
PGE Scores	Physician's Global evaluation (PGE) scores over the treatment period. Scale: 1-2 = Poor, 3-4 = Fair, 5-6 = Good, 7-8 = Excellent The means are adjusted for centre, smoking status at entry and baseline value.	Week 48
PGR Scores	Patient's Global rating (PGR) scores over the treatment period. Scale: 1=much better to 7=much worse The means are adjusted for centre, smoking status at entry and baseline value.	Week 48

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Helpful Links

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Study record dates

Study Major Dates

• Study Start: February 1, 2003
• Primary Completion (Actual): June 1, 2005

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 12, 2005
• First Posted (Estimate): September 15, 2005

Study Record Updates

• Last Update Posted (Estimate): May 20, 2014
• Last Update Submitted That Met QC Criteria: May 15, 2014
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Tiotropium Bromide
• Other Study ID Numbers: 205.255