Conservative Non-Invasive Versus Routine Invasive Management in Coronary Artery Bypass Surgery Patients With Non ST Elevation Elevation Acute Coronary Syndrome (CABG-ACS)
|ClinicalTrials.gov Identifier: NCT01895751|
Recruitment Status : Completed
First Posted : July 10, 2013
Last Update Posted : July 20, 2016
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 or disease||Intervention/treatment||Phase|
|Non ST Elevation Myocardial Infarction Unstable Angina||Procedure: Invasive management||Phase 4|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||60 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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.|
|Study Start Date :||April 2012|
|Primary Completion Date :||July 2016|
|Study Completion Date :||July 2016|
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.
- 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 ]
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.
- Quality of life [ Time Frame: Baseline through longer term follow-up (average follow-up 12 months ]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 ]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 ]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 ]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).
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01895751
|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|
|Principal Investigator:||Colin Berry, MD PhD||University of Glasgow|