Acute Bronchodilator Response of a Single Dose of Atrovent or Berotec on Top of Pharmacodynamic Steady State of Spiriva

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00274066
First received: January 9, 2006
Last updated: October 31, 2013
Last verified: October 2013
  Purpose

To evaluate acute effect of single dose of ipratropium (Atrovent) or fenoterol (Berotec) in comparison to placebo when given to COPD patients on pharmacodynamic steady state of tiotropium (Spiriva)


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: Tiotropium + placebo
Drug: Tiotropium + ipratropium
Drug: Tiotropium + fenoterol
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: The Acute Bronchodilator Effects of a Single Dose (2 Puffs) of the Shortacting Anticholinergic Ipratropium Bromide (40μg) and the Short-acting Beta-adrenergic Fenoterol (200μg) in Comparison to Placebo on Top of Pharmacodynamic Steady State of Once Daily Tiotropium (18μg) Inhalation Capsule in Patients With Chronic Pulmonary Disease (COPD)

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Peak FEV1 response, defined as the peak FEV1 minus the steady-state baseline FEV [ Time Frame: up to 37 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Peak FVC response in the six-hour observation period following administration of the first single dose of randomised treatment [ Time Frame: up to 37 days ] [ Designated as safety issue: No ]
  • FEV1 and FVC response one hour after the second dose of randomised treatment [ Time Frame: up to 37 days ] [ Designated as safety issue: No ]
  • Individual FEV1 and FVC measurements at each time point [ Time Frame: up to 37 days ] [ Designated as safety issue: No ]
  • sGaw and Raw measured at 1 and 6 hour after the first dose of randomised treatment and at 1 hour after the second dose of randomised treatment [ Time Frame: up to 37 days ] [ Designated as safety issue: No ]
  • All adverse events [ Time Frame: up to 37 days ] [ Designated as safety issue: No ]
  • Pulse rate [ Time Frame: up to 37 days ] [ Designated as safety issue: No ]
  • Sitting blood pressure in conjunction with spirometry [ Time Frame: up to 37 days ] [ Designated as safety issue: No ]
  • ECG recorded one hour after the first dose of randomised treatment [ Time Frame: up to 37 days ] [ Designated as safety issue: No ]
  • Physical examination at baseline (Visit 1) and at the conclusion of patient participation in the trial [ Time Frame: up to 37 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 65
Study Start Date: October 2002
Study Completion Date: September 2003
Primary Completion Date: September 2003 (Final data collection date for primary outcome measure)
Detailed Description:

In case mono-bronchodilator therapy does not control symptoms of COPD adequately or if regular maintenance therapy is desired, a therapeutic intervention with a combination of bronchodilators is recommended. The risks of side-effects increases with increasing dose of any drug and, therefore, the most important rationale for combination therapy is a very favourable ratio of efficacy and safety. Knowing that anticholinergic and beta-adrenergic agents achieve their bronchodilating effects by different mechanisms, in particular the combination of these agents has proven to be beneficial in the management of COPD. Based on the established clinical benefits, tiotropium is an attractive and promising agent for the first-line long-term maintenance therapy in COPD. This also implies that a therapeutic intervention with other bronchodilators will be prescribed in daily practice. At present no studies on combination therapy with short-acting agents are available. Therefore, using a double-blind, randomised, crossover design, the bronchodilator effects of single doses of ipratropium or fenoterol were compared with placebo when added on top of steady state tiotropium. Patients were pre-treated with tiotropium to achieve this pharmacodynamic steady state. Serial lung function tests (FEV1, FVC, Raw, sGaw) were conducted following add-on of the short-acting bronchodilators or placebo.

Study Hypothesis:

H0: there is no difference between treatments in mean peak FEV1 H1: there is a difference between treatments in mean peak FEV1

Comparison(s):

Add-on of placebo was compared to add-on of ipratropium or add-on of fenoterol. The comparison of ipratropium with placebo was primary. The other 2 pair-wise comparisons were secondary.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion:

  • diagnosis of COPD
  • FEV1 < 60% of predicted
  • FEV1 < 70% of FVC
  • smoking history of 10 pack-years

Exclusion:

  • significant other disease than COPD
  • history of asthma, allergic rhinitis or blood eosinophil count > 600mm3
  • cardiac arrhythmia requiring drug therapy
  • symptomatic prostatic hypertrophy, bladder neck obstruction or narrow-angle glaucoma
  • recent history of MI (within past year)
  • history of cancer within past 5 years
  • life-threatening pulmonary obstruction
  • cystic fibrosis or bronchiectasis; tuberculosis
  • pulmonary resection
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00274066

Locations
Netherlands
Twenteborg Ziekenhuis
Almelo, Netherlands, 7609 PP
Amphia Ziekenhuis
Breda, Netherlands, 4819 EV
Boehringer Ingelheim Investigational Site
Groningen, Netherlands, 9700 RB
Afdeling longziekten
Winschoten, Netherlands, 9670 RA
Gelre Ziekenhuizen
Zutphen, Netherlands, 7207 BA
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Study Coordinator Boehringer Ingelheim BV/Alkmaar
  More Information

Additional Information:
No publications provided by Boehringer Ingelheim

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00274066     History of Changes
Other Study ID Numbers: 205.258
Study First Received: January 9, 2006
Last Updated: October 31, 2013
Health Authority: Netherlands: IGZ Health Inspection

Additional relevant MeSH terms:
Chronic Disease
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Disease Attributes
Pathologic Processes
Respiratory Tract Diseases
Lung Diseases, Obstructive
Fenoterol
Bronchodilator Agents
Ipratropium
Tiotropium
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Tocolytic Agents
Reproductive Control Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Cholinergic Antagonists
Cholinergic Agents

ClinicalTrials.gov processed this record on April 20, 2014