Conservative Non-Invasive Versus Routine Invasive Management in Coronary Artery Bypass Surgery Patients With Non ST Elevation Elevation Acute Coronary Syndrome (CABG-ACS)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
University of Glasgow
Information provided by (Responsible Party):
Colin Berry, NHS National Waiting Times Centre Board
ClinicalTrials.gov Identifier:
NCT01895751
First received: May 24, 2013
Last updated: July 14, 2013
Last verified: July 2013
  Purpose

Background: Most coronary artery bypass grafts (CABG) are diseased or blocked within 10 years of surgery meaning CABG survivors have an ever increasing risk of recurrent angina, heart attack and death. Given the large number of CABG survivors in the United Kingdom (UK), and the complexities of their clinical management, their heart health problems and related treatment are an increasing challenge in the UK National Health Service (NHS) and worldwide.

There is considerable controversy in the NHS and internationally about how to best manage patients with prior CABG and unstable angina / non-ST elevation acute coronary syndromes (NSTE-ACS). This is because there is no robust evidence to inform treatment practices or clinical guidelines since, historically, these patients have been excluded from randomised trials. This is the rationale for our study.

Aims: Our overall aim is to undertake a clinical trial of conservative non-invasive management with optimal drug therapy versus routine invasive management in NSTE-ACS patients with prior CABG during routine clinical care in NHS hospitals across the UK. Our trial is a proof-of-concept study of feasibility, safety, potential efficacy and health economics.

Hypothesis: A routine invasive approach in NSTE-ACS patients with prior CABG will not be superior to a conservative non-invasive approach with optimal medical therapy.

Design: The pilot study will involve 60 patients recruited in large urban hospitals (Western Infirmary, Glasgow Royal Infirmary) and district general hospitals (Royal Alexandra Hospital, Royal Blackburn Hospital (RBH)) to reflect usual practice in the UK. One of these hospitals (RBH) has an on-site cardiac catheterization laboratory, whereas the other hospitals refer patients who have been triaged for invasive management to the regional cardiothoracic centre (the Golden Jubilee National Hospital). In this proof of concept study, the investigators aim to gather information about screening, recruitment, randomisation, patient characteristics (including comorbidity and quality of life) and initial clinical outcomes to inform the design of the definitive trial. The follow-up will be in line with standard clinical care i.e. 30-42 days and 1 year. The investigators will hold data in the longer term to enable long-term follow-up analyses. The investigators will record information on NSTE-ACS patients with prior CABG who are ineligible to take part or who do not wish to be randomised as part of all follow-up registry of 'all-comers'.


Condition Intervention Phase
Non ST Elevation Myocardial Infarction
Unstable Angina
Procedure: Invasive management
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Clinical Trial of Conservative Versus Routine Invasive Management in Patients With Prior Coronary Artery Bypass Surgery in Patients With a Non-ST Elevation Acute Coronary Syndrome: a Pilot Trial and Registry.

Resource links provided by NLM:


Further study details as provided by NHS National Waiting Times Centre Board:

Primary Outcome Measures:
  • The post-randomization rate of major adverse events (co-primary composite outcome), one composite outcome for EFFICACY and one composite outcome for SAFETY. [ Time Frame: Post randomisation, expected average followup of 1 year ] [ Designated as safety issue: Yes ]

    Each composite outcome (EFFICACY, SAFETY) includes major adverse events. The comparison between the incidence of each outcome according to treatment group will assess the between group difference in the proportion of major adverse events in patients allocated to non-invasive (conservative) management compared to invasive management.

    PRIMARY EFFICACY ENDPOINTS are defined as all-cause mortality, rehospitalization for refractory ischemia/angina, myocardial infarction or heart failure. The endpoints will be assessed during the study until the final randomized patient has completed 1 year follow-up. The events will be adjudicated by an independent Clinical Event Committee.

    PRIMARY SAFETY ENDPOINTS are defined as Bleeding (Bleeding Academic Research Consortium (BARC) types 2-4), stroke, procedure-related MI (Type 4a, Universal Definition), worsening renal function defined as a 25% reduction in glomerular filtration rate (GFR) or hemodialysis during the index hospitalization.



Secondary Outcome Measures:
  • Quality of life [ Time Frame: Baseline through longer term follow-up (average follow-up 12 months ] [ Designated as safety issue: Yes ]
    Quality of life (Euro-quality of life 5 dimensions (EQ-5D) assessed at baseline and at 12 months

  • Health economics [ Time Frame: Baseline through long term followup - average of 12 months ] [ Designated as safety issue: No ]
    Secondary care costs and procedure-related costs (diagnostic tests, PCI, CABG), hospital bed days including Intensive Care Unit, High Dependency Unit, general medical. This will be prospectively recorded for the index and any subsequent hospitalisations.

  • Angina severity assessment with Canadian Cardiovascular Society angina class [ Time Frame: Baseline through long term followup - 12 months average ] [ Designated as safety issue: Yes ]
    Canadian Cardiovascular Society angina class will be recorded at baseline and through follow-up, average of 12 months.

  • Hospitalization for refractory ischemia and/or angina [ Time Frame: Follow-up post-randomization ] [ Designated as safety issue: Yes ]
    Refractory Ischemia / Refractory angina are defined as recurrent ischemic symptoms lasting more than 5 minutes, while on optimal medical therapy (at least 2 anti-anginal treatments) with documented characteristic ECG changes indicative of ischaemia and requiring an additional intervention. An additional intervention was defined as reperfusion therapy for MI, cardiac catheterization, insertion of intra-aortic balloon pump or revascularization procedure (PCI or CABG surgery) within 48 hours of the onset of this episode. This definition is in line with the Timing of Intervention in Acute Coronary Syndromes (TIMACS) trial (NEJM 2009;360:2165-75).


Estimated Enrollment: 60
Study Start Date: April 2012
Estimated Study Completion Date: June 2019
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Conservative therapy

Conservative therapy group involves optimal medical therapy according to local hospital protocols with selective invasive management as clinically appropriate. Patients assigned to the conservative group may be referred for invasive management if the patient meets one of the following pre-specified criteria:

Recurrent or refractory (class III or IV) angina with documented ischaemic ECG changes while on "optimal" medical therapy.

New ST segment elevation in two contiguous leads without Q waves or T wave inversion greater than 3 mm or development of hemodynamic instability Deterioration in heart failure status (defined as Killip class 3 or 4).

Active Comparator: Invasive management
Invasive management is timed as appropriate according to local NHS protocols. Usually, invasive management is expected to be performed in line with contemporary guidelines.
Procedure: Invasive management
Invasive management includes coronary and graft angiography (diagnostic imaging test) and coronary and/or graft revascularization with percutaneous coronary intervention (PCI) and/or coronary artery bypass graft (CABG), as clinically appropriate.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Unstable angina or non-ST elevation myocardial infarction
  2. Stabilised symptoms without recurrent chest pain or IV therapy for 12 hrs when ambulant.

Exclusion Criteria:

  1. Refractory ischaemia (i.e. recurrent angina with minimal exertion or at rest (i.e. Canadian Cardiovascular Society class III or IV) not controlled by medical therapy)
  2. Cardiogenic shock
  3. Inability to give informed consent
  4. Unsuitable for invasive management.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01895751

Locations
United Kingdom
Royal Blackburn Hospital
Blackburn, East Lancashire, United Kingdom, BB2 3HH
Royal Alexandra Hospital, Corsebar Road, Paislay
Glasgow, Scotland, United Kingdom, PA2 9PN
Western Infirmary, Dumbarton Road
Glasgow, United Kingdom, G11 6NT
Glasgow Royal Infirmary, 84 Castle St
Glasgow, United Kingdom, G4 0SF
Golden Jubilee National Hospital, Clydebank, Dunbartonshire
Glasgow, United Kingdom, G81 4DY
Sponsors and Collaborators
NHS National Waiting Times Centre Board
University of Glasgow
Investigators
Principal Investigator: Colin Berry, MD PhD University of Glasgow
  More Information

Additional Information:
Publications:

Responsible Party: Colin Berry, Professor Colin Berry, NHS National Waiting Times Centre Board
ClinicalTrials.gov Identifier: NCT01895751     History of Changes
Other Study ID Numbers: GN-11-CA456
Study First Received: May 24, 2013
Last Updated: July 14, 2013
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by NHS National Waiting Times Centre Board:
Non-ST elevation myocardial infarction (NSTEMI)
Non-ST elevation acute coronary syndrome (NSTE-ACS)
Unstable Angina
Medical therapy
Coronary angiogram
Percutaneous coronary intervention
Coronary artery bypass surgery
Coronary revascularization
Health economics

Additional relevant MeSH terms:
Infarction
Syndrome
Myocardial Infarction
Acute Coronary Syndrome
Angina, Unstable
Ischemia
Pathologic Processes
Necrosis
Disease
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Angina Pectoris
Chest Pain
Pain
Signs and Symptoms

ClinicalTrials.gov processed this record on September 18, 2014