Preventing Adverse Cardiac Events in COPD

NCT03917914 | Completed Phase 3 DMC

• 1 other identifier: PACE in COPD
• Study Type: interventional
• Target: 280
• Locations: 4 countries
• Sites: 24

Brief Summary

A double-blind, randomised controlled trial in participants with COPD to assess the efficacy of proactive treatment of cardiac risk in people with COPD. We hypothesise that treating known and undiagnosed CVD in COPD participants will improve both cardiac and respiratory outcomes.

Conditions

Chronic Obstructive Pulmonary Disease; Cardiovascular Diseases

Keywords

COPD; MACE

Outcome Measures

Primary Outcomes (10)

• All-cause mortality

  Composite outcome of the following that will be analysed using a win-ratio apprach according to clinical importance

  Baseline to 24 months

• Hospitalisation for COPD exacerbation

  Baseline to 24 months

• Hospitalisation for primary cardiac cause (ischaemia, arrhythmia, heart failure or ischaemic stroke)

  Baseline to 24 months

• Moderate COPD exacerbation - not hospitalised by treated with oral corticosteroids/antibiotics or both

  Baseline to 24 months

• Cardiac Hospitalisation for cardiac cause other than ischemia, arrythmia or heart failure

  Baseline to 24 months

• Respiratory hospitalisation for a respiratory cause other than COPD exacerbation

  Baseline to 24 months

• Decrease in FEV1 or greatest FEV1% drop - largest decrease in FEV1 from post-bronchodiliator spirometry at baseline

  Baseline to 24 months

• Mild COPD exacerbation - treated with increased inhalers/inhaler technique/addition of theophylline

  Baseline to 24 months

• Higher SGRQ score (clinically important change >= 4)

  Baseline to 12 and 24 months

• Higher CAT score (clinically important change >= 2)

  Baseline to 12 and 24 months

Secondary Outcomes (14)

• Time to first moderate-severe COPD Exacerbation

  Baseline to 24 months

• Severe (hospital admission) COPD exacerbation rate (annualised)

  Baseline to 24 months

• Number of events of composite (annualised) cardio-respiratory hospital admissions and MACE

  Baseline to 24 months

• Quality of life assessed by St George's Respiratory Questionnaire (SGRQ)

  Baseline to 24 months

• EuroQoL Group 5-5 Dimension self-report questionnaire (EQ-5D-5L) to assess health state utilities

  Baseline to 24 months

Study Arms (2)

Bisoprolol

ACTIVE COMPARATOR

1.25, 2.5 or 5mg of bisoprolol daily

Drug: Bisoprolol

Placebo

PLACEBO COMPARATOR

1.25, 2.5 or 5mg of matched placebo daily

Drug: Placebo Oral Tablet

Interventions

Bisoprolol DRUG

As in arm description

Bisoprolol

Placebo Oral Tablet DRUG

As in arm description

Placebo

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants will be eligible for this study if they qualify on all of the following:
• Have provided written informed consent
• Have COPD defined by the 2019 Global Initiative for Chronic Obstructive Lung Disease (GOLD) diagnostic criteria
• Aged 40-85 years
• FEV1 ≥30% and ≤70% predicted post-bronchodilator
• FEV1/FVC \<0.7 post-bronchodilator
• Have had a COPD exacerbation in the previous 24 months requiring oral corticosteroid, antibiotics, or both
• If taking maintenance OCS, dosage is stable and ≤10mg daily for 4 weeks prior to randomisation
• Resting SBP ≥100mmHg
• SBP and spirometry criteria must be met after the test dose of bisoprolol of 1.25mg
• (New Zealand only) A history of cardiovascular disease, including heart failure, ischaemic heart disease, tachyarrhythmias, and hypertension

You may not qualify if:

• Participants will be ineligible for the study if they have any of the following:
• Concurrent therapy with any other β-blocker
• Resting HR \<60bpm
• Unstable left HF (i.e. symptomatic and/or necessary change in management in the last 12 weeks, or in clinicians' opinion)
• Clinically significant pulmonary hypertension, which in the investigator's opinion would be a contraindication for β-blocker therapy
• Severe end-stage peripheral vascular disease
• nd or 3rd degree heart block
• Currently using or have been prescribed LTOT or resting saturated oxygen level \<90% when stable
• Expected survival is less than 12 months, or in the investigator's opinion, the person has such unstable disease (of any type) that maintaining 12 months' participation would be unlikely
• Clinical instability since a MACE in the previous 12 weeks
• Lower respiratory tract infection or AECOPD within the last 8 weeks
• COPD not clinically stable as determined by the investigator
• In the clinician's view, have asthma-COPD overlap or co-existent asthma are present; or an improvement in FEV1 ≥400mL post-bronchodilator is observed on two occasions
• Females of child-bearing age and capability who are pregnant or breastfeeding or those in this group not using adequate birth control
• Coexistent illness which precludes participation in the study (poorly controlled diabetes, active malignancy)

Sponsors & Collaborators

• The George Institute: lead
• National Health and Medical Research Council, Australia: collaborator

Study Sites (24)

Campbelltown Hospital

Campbelltown, New South Wales, 2560, Australia

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

John Hunter Hospital & Hunter Medical Research Institute

Newcastle, New South Wales, 2305, Australia

Location

Concord Repatriation General Hospital

Sydney, New South Wales, 2139, Australia

Location

Westmead Hospital

Sydney, New South Wales, 2145, Australia

Location

Prince Charles Hospital

Brisbane, Queensland, 4032, Australia

Location

Princess Alexandra Hospital

Brisbane, Queensland, 4102, Australia

Location

Gold Coast University Hospital

Southport, Queensland, 4215, Australia

Location

Fiona Stanley Hospital

Murdoch, Washington, 6150, Australia

Location

TrialsWest Pty Ltd

Perth, Washington, 6000, Australia

Location

Institute for Respiratory Health

Perth, Washington, 6009, Australia

Location

Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences

Rohtak, Haryana, India

Location

St John's Medical College Hospital

Bangalore, India

Location

Postgraduate Institute of Medical Education and Research

Chandigarh, India

Location

All India Institute of Medical Sciences

New Delhi, India

Location

Middlemore Hospital

Auckland, 2025, New Zealand

Location

University of Otago

Christchurch, 8011, New Zealand

Location

Dunedin Hospital

Dunedin, 9054, New Zealand

Location

Waikato Hospital

Hamilton, 3240, New Zealand

Location

Medical Research Institute of New Zealand

Wellington, 6021, New Zealand

Location

Central Chest Clinic - Borella

Colombo, Sri Lanka

Location

Central Chest Clinic

Colombo, Sri Lanka

Location

Kandy National Hospital

Kandy, Sri Lanka

Location

National Institute of Respiratory Diseases

Welisara, Sri Lanka

Location

Related Publications (2)

• Jenkins CR, Martin A, Chang CL, Beasley R, Wrobel JP, McDonald VM, Dobler CC, Yang IA, Farah CS, Cochrane B, Hillis GS, Polak Scowcroft C, Ranasinha CD, De Silva HA, Aggarwal AN, Billot L, Devaux A, Gianacas C, Galgey S, Hancox RJ; PACE investigators. Bisoprolol to prevent adverse cardiac events (PACE) in COPD: a multicentre, double-blind, randomised, controlled, phase 3 trial. Lancet Respir Med. 2026 Jan 21:S2213-2600(25)00390-X. doi: 10.1016/S2213-2600(25)00390-X. Online ahead of print.

  PMID: 41579873 DERIVED

• Martin A, Hancox RJ, Chang CL, Beasley R, Wrobel J, McDonald V, Dobler CC, Yang IA, Farah CS, Cochrane B, Hillis GS, Scowcroft CP, Aggarwal A, Di Tanna GL, Balicki G, Galgey S, Jenkins C. Preventing adverse cardiac events (PACE) in chronic obstructive pulmonary disease (COPD): study protocol for a double-blind, placebo controlled, randomised controlled trial of bisoprolol in COPD. BMJ Open. 2021 Aug 27;11(8):e053446. doi: 10.1136/bmjopen-2021-053446.

  PMID: 34452971 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Cardiovascular Diseases

Interventions

Bisoprolol

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

Study Officials

• Prof Christine Jenkins

  The George Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2019
• First Posted: April 17, 2019
• Study Start: June 30, 2020
• Primary Completion: March 31, 2025
• Study Completion: March 31, 2025
• Last Updated: May 16, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

SR (4); NZ (5); AU (11); IN (4)