Beta Blocker Therapy in Moderate to Severe COPD

NCT01656005 | Completed Phase 4

• 2 other identifiers: ANDA22011-006008-11
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

COPD; Beta blockers; Cardioselective; Non-cardioselective; Impulse oscillometry

Outcome Measures

Primary Outcomes (1)

• Change in airway resistance at 5HZ (R5) using impulse oscillometry from baseline.

  4, 5 and 6 weeks of each treatment period

Secondary Outcomes (6)

• Change in remaining impulse oscillometry measurements from baseline

  4, 5 and 6 weeks of each treatment period

• Change in spirometry measurements from baseline

  4, 5 and 6 weeks of each treatment period

• Change in echocardiogram parameters from baseline

  At 6 weeks of each treatment period

• Change in vital signs from baseline

  4, 5, and 6 weeks in each treatment period

• Change in six minute walk test distance from baseline

  4, 5 and 6 weeks of each treatment periods.

Other Outcomes (6)

• Daily domiciliary measurements - trends over course of study

  Twice daily measurements

• Change in serum B-type natriuretic peptide (BNP) from baseline

  6 weeks in each treatment period

• Change in serum aldosterone levels from baseline

  6 weeks in each treatment period

Study Arms (2)

Carvedilol

EXPERIMENTAL

Beclometasone/Formoterol Beclometasone Tiotropium

Drug: Carvedilol; Drug: Beclometasone/formoterol; Drug: Tiotropium; Drug: Beclometasone

Bisoprolol

ACTIVE COMPARATOR

Beclometasone/Formoterol Beclometasone Tiotropium

Drug: Bisoprolol; Drug: Beclometasone/formoterol; Drug: Tiotropium; Drug: Beclometasone

Interventions

Carvedilol DRUG

Dose titration: 3.125mg bid for 1 week, 6.25mg bid for 1 week, 12.5mg bid for 4 weeks.

Carvedilol

Bisoprolol DRUG

Dose titration: 1.25mg od for 1 week, 2.5mg od for 1 week, 5mg for 4 weeks.

Bisoprolol

Beclometasone/formoterol DRUG

2 puffs bid for first 5 weeks in each treatment arm

Also known as: Fostair 100/6

Bisoprolol; Carvedilol

Tiotropium DRUG

1 puff daily for first 4 weeks of each treatment arm

Also known as: Spiriva 18mcg

Bisoprolol; Carvedilol

Beclometasone DRUG

2 puffs bid for final week (week 6) of each treatment arm

Also known as: Clenil 200

Bisoprolol; Carvedilol

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Dundee: lead
• Tenovus Scotland: collaborator

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)

• Jabbal S, Anderson W, Short P, Morrison A, Manoharan A, Lipworth BJ. Cardiopulmonary interactions with beta-blockers and inhaled therapy in COPD. QJM. 2017 Dec 1;110(12):785-792. doi: 10.1093/qjmed/hcx155.

  PMID: 29025008 RESULT

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Carvedilol; Bisoprolol; Beclomethasone; Formoterol Fumarate; Tiotropium Bromide

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)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 3-Ring; Phenoxypropanolamines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Chlorinated; Ethanolamines; Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Alkaloids; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Study Officials

• William J Anderson, MBChB

  University of Dundee

  PRINCIPAL INVESTIGATOR

• Brian J Lipworth, MD

  University of Dundee

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2012
• First Posted: August 2, 2012
• Study Start: August 1, 2012
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: April 23, 2019

Record last verified: 2019-04

Locations

GB (1)