Beta-blockers to Patients With Chronic Obstructive Pulmonary Disease

NCT03566667 | Active Not Recruiting Phase 4 DMC

• 1 other identifier: BRONCHIOLE-2017
• Study Type: interventional
• Target: 1,713
• Locations: 1 country
• Sites: 1

Brief Summary

Background: In patients with chronic obstructive pulmonary disease (COPD) and concomitant cardiovascular conditions cardio-selective beta-blockers reduce mortality and can be used without significant negative effects on lung function or respiratory symptoms. Observational studies indicate that beta-blocker therapy in COPD even without overt cardiovascular disease, is associated with reduced risk for mortality and COPD exacerbations. Aim: The overall purpose of our study is to examine the benefit of general beta-blocker therapy on important patient-oriented measures in chronic obstructive pulmonary disease (COPD). Our primary hypothesis that treatment with beta-blockers in patients with COPD and no comorbid heart disease at baseline can prevent a Composite measure of hospitalizations due to cardiovascular diseases, COPD exacerbations and death. Population: 1700 patients with C OPD. Inclusion criteria are FEV1/FVC \< 70, age \>40 years and sinus rhythm 50-120/min. Exclusion criteria include hypersensitivity against metoprolol, atrioventricular (AV) block II or II or sick sinus syndrome without pacemaker, atrial fibrillation or flutter, clinical signs of or previously known cardiovascular disease, systolic blood pressure \< 90, severe asthma, present beta-blocker therapy or ongoing COPD exacerbation. Intervention: Metoprolol at a target dose of 100 mg in addition to standard COPD care. Control: No placebo control. Randomized, pragmatic un-blinded controlled study where the control Group receives standard COPD care. Outcome: The primary outcome is a composite measure of all-cause mortality, C OPD exacerbations, and cardiovascular events after one year. Endpoint data from Swedish national registries and clinical follow-up. Importance: Beta-blocker treatment to attenuate morbidity in patients with COPD could have great clinical and social importance at a low cost.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

Beta-blockers

Outcome Measures

Primary Outcomes (1)

• Mortality, exacerbations and cardiovascular events

  A composite measure of all-cause mortality, COPD exacerbations and cardiovascular events after one year

  One year

Secondary Outcomes (3)

• Mortality

  One year

• Exacerbations

  One year

• Cardiovascular events

  One year

Study Arms (2)

Metoprolol

ACTIVE COMPARATOR

Metoprolol at an aimed dose of 100 mg in addition to usual standard care

Drug: Metoprolol

Standard care

OTHER

Usual standard care

Drug: Standard care

Interventions

Metoprolol DRUG

Betablocker

Metoprolol

Standard care DRUG

Standard care

Also known as: Usual standard care

Standard care

Eligibility Criteria

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

You may qualify if:

• A diagnosis of COPD confirmed by spirometry showing post bronchodilator value of Forced Expiratory Volume in one second (FEV1)//Forced Vital Capacity (FVC) \< 70 according to the Global Initiative on Obstructive Pulmonary Disease (GOLD)
• ≥40 years of age

You may not qualify if:

• Known hypersensitivity to metoprolol or related derivatives
• AV block II or III unless treated with a pacemaker
• Sinus bradycardia (resting heart rate \<50/min)
• Sick sinus syndrome unless treated with a pacemaker
• Atrial fibrillation/flutter
• Clinical signs of or a previous diagnosis of heart failure, angina pectoris, myocardial infarction, cerebrovascular disease or critical peripheral ischemia
• Systolic blood pressure \<90 mmHg
• Any tachy-arrythmias other than sinus rhythm
• Sinus tachycardia \>120 / min
• Systolic blood pressure \<90 mmHg
• Severe bronchial asthma
• Current beta-blocker treatment
• Inability to provide informed consent
• Age below 40 years
• Acute on-going exacerbation of COPD

Sponsors & Collaborators

• Ole Frobert, MD, PhD: lead

Study Sites (1)

University Hospital of Örebro

Örebro, 701 85, Sweden

Location

Related Publications (5)

• Short PM, Lipworth SI, Elder DH, Schembri S, Lipworth BJ. Effect of beta blockers in treatment of chronic obstructive pulmonary disease: a retrospective cohort study. BMJ. 2011 May 10;342:d2549. doi: 10.1136/bmj.d2549.

  PMID: 21558357 RESULT

• Salpeter S, Ormiston T, Salpeter E. Cardioselective beta-blockers for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2005 Oct 19;2005(4):CD003566. doi: 10.1002/14651858.CD003566.pub2.

  PMID: 16235327 RESULT

• Dransfield MT, Rowe SM, Johnson JE, Bailey WC, Gerald LB. Use of beta blockers and the risk of death in hospitalised patients with acute exacerbations of COPD. Thorax. 2008 Apr;63(4):301-5. doi: 10.1136/thx.2007.081893. Epub 2007 Oct 19.

  PMID: 17951276 RESULT

• Rutten FH, Zuithoff NP, Hak E, Grobbee DE, Hoes AW. Beta-blockers may reduce mortality and risk of exacerbations in patients with chronic obstructive pulmonary disease. Arch Intern Med. 2010 May 24;170(10):880-7. doi: 10.1001/archinternmed.2010.112.

  PMID: 20498416 RESULT

• Sundh J, Magnuson A, Montgomery S, Andell P, Rindler G, Frobert O; BRONCHIOLE investigators. Beta-blockeRs tO patieNts with CHronIc Obstructive puLmonary diseasE (BRONCHIOLE) - Study protocol from a randomized controlled trial. Trials. 2020 Jan 30;21(1):123. doi: 10.1186/s13063-019-3907-1.

  PMID: 32000825 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Metoprolol; Standard of Care

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; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Ole Fröbert, MD, PhD

  Region Örebro County

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Pragmatic randomized controlled trial

Study Record Dates

• First Submitted: June 12, 2018
• First Posted: June 25, 2018
• Study Start: June 12, 2018
• Primary Completion: December 1, 2025
• Study Completion: April 30, 2026
• Last Updated: April 3, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)