Chronic Beta-blockade and Cardiopulmonary Exercise in COPD

NCT02380053 | Completed Phase 4

• 3 other identifiers: CPET12015-000207-132012RC22
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

What are the differential effects of beta-blockers on lung and heart function during exercise in chronic obstructive pulmonary disease (COPD)? COPD is a major cause of illness and death. Not only do these individuals suffer from lung disease, but COPD often leads to other illnesses, particularly heart disease. Beta-blockers very successfully treat heart disease. It is therefore logical that one would want to use this treatment in COPD patients with heart disease too. However, there has always been concern that beta-blockers could cause significant problems in COPD by worsening lung function, as these can have the opposite effect to inhalers used to treat COPD that open up airways. Pointedly, there is increasing evidence that despite this problem, COPD patients who have been prescribed beta-blockers have been shown to gain benefit particularly in terms of preventing death. In this study, the investigators therefore want to examine which beta-blocker might be the safest for COPD patients, as each work slightly differently. Some beta-blockers may have a more beneficial effect on airways than others, whilst still benefitting the heart. The investigators will study two different beta-blockers; one that potentially narrows airways and one that potentially opens airways. The investigators will be using cardiopulmonary exercise testing (an exercise bike that measures both heart and lung function during exercise) to look for differences between both beta-blockers primarily in terms of lung function but also with information about the heart. The investigators will recruit people with moderate to severe COPD who are able to complete a cycle exercise test through their respiratory research department. The study will last for 10-12 weeks with 5 main visits to the department for serial exercise tests, breathing tests, simple heart function tests and simple blood tests that will tell the investigators what other effects these beta-blockers are having on the heart and lungs.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

Beta-blocker; Cardiopulmonary exercise testing

Outcome Measures

Primary Outcomes (1)

• Change in Inspiratory Capacity (IC) from rest to isotime peak.

  The primary outcome for this study will be the difference from baseline in the change in Inspiratory Capacity (IC) from rest to isotime peak (i.e. same time point during endurance exercise test) between beta-blocker treatments at 4 weeks. This will evaluate any differences in dynamic hyperinflation during exercise between treatments.

  Baseline to 4 weeks

Secondary Outcomes (33)

• Exercise outcome: Oxygen uptake at peak exercise (VO2peak)

  Baseline to 4 weeks.

• Exercise outcome: Anaerobic threshold (AT)

  Baseline to 4 weeks.

• Exercise outcome: Heart rate

  Baseline to 4 weeks.

• Exercise outcome: Heart rate reserve (HRR)

  Baseline to 4 weeks.

• Exercise outcome: Heart rate recovery (HRrec)

  Baseline to 4 weeks.

Study Arms (2)

Bisoprolol

EXPERIMENTAL

2.5mg once daily for 2 weeks then 5mg once daily for 2 weeks.

Drug: Bisoprolol

Celiprolol

EXPERIMENTAL

200mg once daily for 2 weeks then 400mg once daily for 2 weeks.

Drug: Celiprolol

Interventions

Bisoprolol DRUG

2 weeks of Bisoprolol 2.5mg daily then 2 weeks Bisoprolol 5mg daily

Bisoprolol

Celiprolol DRUG

2 weeks of Celiprolol 200mg daily then 2 weeks Celiprolol 400mg daily

Celiprolol

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female volunteers aged 40-80 years
• Stable moderate to severe COPD (Global initiative on Obstructive Lung Disease \[GOLD\] stage 2/3)
• Post-bronchodilator FEV1 30-80% predicted
• FEV1/FVC ratio \<70%
• Stable defined as no exacerbation in previous 1 month
• Smoking history ≥10 pack-years
• Oxygen saturations ≥92% on room air at rest
• Electrocardiogram demonstrating sinus rhythm.

You may not qualify if:

• Use of domiciliary oxygen
• History of other primary obstructive lung disease including asthma or bronchiectasis
• Hospitalisation with exacerbation of COPD within past 3 months
• History of unstable angina, uncontrolled hypertension or heart failure (New York Heart Association class 3-4)
• Overt clinical signs of right heart failure
• Average resting systolic BP\<110mmHg or average resting HR\<55bpm
• Pregnancy or lactation
• Known or suspected sensitivity to/intolerance of investigational medicinal product
• Inability to comply with compulsory aspects of protocol
• Any degree (first, second or third) of heart block
• Sino-atrial block
• Sick sinus syndrome
• Severe forms of peripheral arterial occlusive disease or severe forms of Raynaud's syndrome
• Untreated phaeochromocytoma
• Severe renal impairment (eGFR\<15ml/min)

Sponsors & Collaborators

• University of Dundee: lead

Study Sites (1)

Asthma and Allergy Research Group, Ninewells Hospital and Medical School, University of Dundee

Dundee, DD1 9SY, United Kingdom

Location

Related Publications (1)

• Anderson W, Short P, Ross R, Lipworth BJ. Bisoprolol versus celiprolol on dynamic hyperinflation, cardiopulmonary exercise and domiciliary safety in COPD: a single-centre, randomised, crossover study. BMJ Open Respir Res. 2023 Jul;10(1):e001670. doi: 10.1136/bmjresp-2023-001670.

  PMID: 37451701 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Bisoprolol; Celiprolol

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• William J Anderson, MBCHB

  University of Dundee / NHS Tayside

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Respiratory Physician and Honorary Senior Lecturer

Study Record Dates

• First Submitted: February 19, 2015
• First Posted: March 5, 2015
• Study Start: June 7, 2016
• Primary Completion: April 30, 2019
• Study Completion: April 30, 2019
• Last Updated: June 24, 2019

Record last verified: 2019-06

Locations

GB (1)