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Beta Blocker Therapy in Moderate to Severe COPD (ANDA2)

This study is not yet open for participant recruitment.
Verified August 2012 by University of Dundee
Sponsor:
Collaborator:
Tenovus Scotland
Information provided by (Responsible Party):
William J Anderson, University of Dundee
ClinicalTrials.gov Identifier:
NCT01656005
First received: July 31, 2012
Last updated: August 27, 2012
Last verified: August 2012
History of Changes
  Purpose

Beta blockers are a type of medication mainly used for heart disease. They are commonly used to treat 'angina' and to prevent heart attacks. Patients with COPD are more likely to suffer from heart disease and so already benefit from this treatment for this reason. In addition to this, new research suggests that there may be further benefit of using beta blockers for COPD, even without also having heart disease.

The reason why beta blockers are not widely used in COPD at present is because of their potential to make symptoms of COPD worse by causing the airways to narrow. Beta blockers are the opposite type of medication to 'beta-agonists' such as salbutamol which you may be taking for symptoms of breathlessness or wheezing. Nevertheless beta blockers are still used in COPD where the benefits (for example heart disease) outweigh any risks.

Current COPD treatment includes inhaled steroids and long acting beta agonists, often given in a combination inhaler (e.g. Seretide or Symbicort) to treat both airway inflammation and airway narrowing, leading to improvement in symptoms. Another drug commonly used is Tiotropium (Spiriva) which is another type of long acting inhaler medication to help with widening the airways.

In this study, we wish to find out if two different types of beta blocker cause different effects on the airways in COPD patients. One type of beta blocker is more 'selective' in acting mainly on the heart, with the other type having more general or 'non-selective' effects on both the heart and lungs. By doing this we will also be able to look at how the beta blockers work alongside the 'usual' inhaler treatment described above.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
 Biological: Carvedilol
Biological: Bisoprolol
Biological: Beclometasone/formoterol
Biological: Tiotropium
Biological: Beclometasone
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of Effects of Chronic Dose Exposure to Cardioselective and Non-cardioselective Beta Blockers on Measures of Cardiopulmonary Function in Moderate to Severe COPD.

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Dundee:

Primary Outcome Measures:
  • Change in airway resistance at 5HZ (R5) using impulse oscillometry from baseline. [ Time Frame: 4, 5 and 6 weeks of each treatment period ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change in remaining impulse oscillometry measurements from baseline [ Time Frame: 4, 5 and 6 weeks of each treatment period ] [ Designated as safety issue: Yes ]
    Resistance at 20Hz (R20); Reactance at 5Hz (X5); Area under reactance curve (Ax); Resonant frequency (Fres).

  • Change in spirometry measurements from baseline [ Time Frame: 4, 5 and 6 weeks of each treatment period ] [ Designated as safety issue: Yes ]
    Forced expiratory volume in 1 sec (FEV1); Forced vital capacity (FVC); Slow vital capacity; Forced expiratory flow between 25-75% of FVC (FEF25-75)

  • Change in echocardiogram parameters from baseline [ Time Frame: At 6 weeks of each treatment period ] [ Designated as safety issue: No ]
    Left ventricular function, right ventricular function, pulmonary pressure, pulmonary acceleration time.

  • Change in vital signs from baseline [ Time Frame: 4, 5, and 6 weeks in each treatment period ] [ Designated as safety issue: Yes ]
    Resting oxygen saturations, heart rate, office blood pressure,

  • Change in six minute walk test distance from baseline [ Time Frame: 4, 5 and 6 weeks of each treatment periods. ] [ Designated as safety issue: No ]
  • Change in St George's Respiratory Questionnaire score from baseline [ Time Frame: 4, 5 and 6 weeks in each treatment arm ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Daily domiciliary measurements - trends over course of study [ Time Frame: Twice daily measurements ] [ Designated as safety issue: Yes ]
    Forced expiatory volume in 1 sec (FEV1); symptom diary; reliever use diary (number of puffs); oxygen saturations; heart rate.

  • Change in serum B-type natriuretic peptide (BNP) from baseline [ Time Frame: 6 weeks in each treatment period ] [ Designated as safety issue: No ]
  • Change in serum aldosterone levels from baseline [ Time Frame: 6 weeks in each treatment period ] [ Designated as safety issue: No ]
  • Change in serum angiotensin II levels from baseline [ Time Frame: 6 weeks in both treatment arms ] [ Designated as safety issue: No ]
  • Change in serum brain-derived neurotrophic factor (BDNF) from baseline [ Time Frame: Weeks 5 and 6 in both treatment periods ] [ Designated as safety issue: No ]
  • Change in serum potassium levels from baseline [ Time Frame: Weeks 5 and 6 of each treatment period ] [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: August 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Carvedilol
Beclometasone/Formoterol Beclometasone Tiotropium
 Biological: Carvedilol
Dose titration: 3.125mg bid for 1 week, 6.25mg bid for 1 week, 12.5mg bid for 4 weeks.
Biological: Beclometasone/formoterol
2 puffs bid for first 5 weeks in each treatment arm
Other Name: Fostair 100/6
Biological: Tiotropium
1 puff daily for first 4 weeks of each treatment arm
Other Name: Spiriva 18mcg
Biological: Beclometasone
2 puffs bid for final week (week 6) of each treatment arm
Other Name: Clenil 200
Active Comparator: Bisoprolol
Beclometasone/Formoterol Beclometasone Tiotropium
 Biological: Bisoprolol
Dose titration: 1.25mg od for 1 week, 2.5mg od for 1 week, 5mg for 4 weeks.
Biological: Beclometasone/formoterol
2 puffs bid for first 5 weeks in each treatment arm
Other Name: Fostair 100/6
Biological: Tiotropium
1 puff daily for first 4 weeks of each treatment arm
Other Name: Spiriva 18mcg
Biological: Beclometasone
2 puffs bid for final week (week 6) of each treatment arm
Other Name: Clenil 200

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Moderate to severe COPD (GOLD stage 2 and 3)
  • FEV1 30-80% predicted
  • No exacerbation in previous 3 months
  • Smoking history ≥ 10 pack years
  • Oxygen saturations≥ 92% on room air at rest
  • ECG demonstrating sinus rhythm

Exclusion Criteria:

  • Use of domiciliary oxygen
  • History of other primary obstructive lung disease including asthma or bronchiectasis
  • History of unstable angina, uncontrolled hypertension or heart failure NYHA class 3-4
  • Overt clinical signs of right heart failure
  • Average resting systolic BP<110mmHg
  • Average resting HR<60bpm
  • Pregnancy or lactation
  • Known or suspected sensitivity to/intolerance of investigational medicinal product
  • Inability to comply with compulsory aspects of protocol
  • Any degree of heart block
  • Concomitant prescription of beta-blockers, rate-limiting calcium channel blockers, digoxin or amiodarone
  • Any clinically significant medical condition that may endanger the health or safety of the participant, or jeopardise the protocol
  • Participation in another trial within the previous 30 days
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01656005

Contacts
Contact: William J Anderson, MBChB 00441382383902 aarg@dundee.ac.uk
Contact: Patricia Burns, BSc MICR 00441382383902 aarg@dundee.ac.uk

Locations
United Kingdom
Asthma and Allergy Research Group, Ninewells Hospital and Medical School, University of Dundee Not yet recruiting
Dundee, United Kingdom, DD1 9SY
Principal Investigator: William J Anderson, MBChB            
Sponsors and Collaborators
University of Dundee
Tenovus Scotland
Investigators
Principal Investigator: William J Anderson, MBChB University of Dundee
Study Director: Brian J Lipworth, MD University of Dundee
  More Information

No publications provided

Responsible Party: William J Anderson, Clinical Research Fellow, University of Dundee
ClinicalTrials.gov Identifier: NCT01656005     History of Changes
Other Study ID Numbers: ANDA2, 2011-006008-11
Study First Received: July 31, 2012
Last Updated: August 27, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by University of Dundee:
COPD
Beta blockers
Cardioselective
Non-cardioselective
Impulse oscillometry

Additional relevant MeSH terms:
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Adrenergic beta-Antagonists
Bisoprolol
Carvedilol
Beclomethasone
Formoterol
Tiotropium
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
 Pharmacologic Actions
Physiological Effects of Drugs
Anti-Inflammatory Agents
Therapeutic Uses
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Asthmatic Agents
Respiratory System Agents
Antihypertensive Agents
Cardiovascular Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic beta-1 Receptor Antagonists

ClinicalTrials.gov processed this record on May 21, 2013