Chronic Beta-blockade and Cardiopulmonary Exercise in COPD

• Status: Completed
• Trial end date: 2019-04-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Dundee
• Treatments: Bisoprolol; Celiprolol

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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)

• Concomitant prescription of beta-blockers, rate-limiting calcium channel blockers, digoxin, 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