Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease-2 (CE-MARC2)

May 1, 2018 updated by: Professor JP Greenwood, University of Leeds

Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease - 2 (CE-MARC2)

CE-MARC 2 is a randomised controlled trial to determine diagnosis and patient management in patients presenting to outpatient clinics with suspected stable angina. Cardiac Magnetic Resonance Imaging (at 3Tesla) will be evaluated prospectively against current best clinical practice (defined by international guidelines). The study hypothesis is that 3Tesla CMR-guided management of patients with suspected stable angina is superior to current clinical practice based on 1) the principles of the National Institutes for Clinical Excellence (NICE) CG95 guidelines (2010); 2) SPECT AHA appropriateness criteria, in terms of avoiding study-defined unnecessary invasive coronary angiography.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The study is a randomized controlled trial of non-invasive imaging to determine diagnosis and management of patients presenting with suspected stable angina. Despite the widespread availability of non-invasive imaging and guideline-enshrined use of optimal medical therapy (OMT), patients with suspected coronary heart disease (CHD) often end up having invasive coronary angiography early in their disease course. Currently >50% of elective invasive coronary angiograms performed in the UK and US do not lead on to a revascularisation procedure (data from 2008-09 UK Hospital Episode Statistics; American College of Cardiology National Cardiovascular Data Registry (Patel MR, et al., N Engl J Med 2010;362:886-95)). The UK NICE guidelines for the management of chest pain of recent onset (CG95; 2010) could increase this proportion even further. This is inefficient for patients and also of healthcare resources.

More widespread use of non-invasive functional imaging could reduce the rates of unnecessary angiography. We have shown in the CE-MARC study (Lancet 2012) that cardiovascular magnetic resonance (CMR) at 1.5Tesla has a higher diagnostic accuracy for the detection of CHD than single-photon emission computed tomography (SPECT). CE-MARC 2 will be a three-way randomised controlled trial of patient management in 1200 patients with known or suspected CHD, comparing 3Tesla CMR to SPECT-guided care or NICE guidelines-based management. The primary endpoint will be the reduction of unnecessary invasive angiography (defined by invasive FFR) at 12 months - identified by our expert patients as an important 'patient focused' clinical outcome measure. The secondary objectives will include: 1) assessment of safety of a CMR-guided management strategy 2) cost effectiveness analysis of these strategies.

Study Type

Interventional

Enrollment (Actual)

1202

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Bristol, United Kingdom
        • University Hospitals Bristol NHS FT
      • Glasgow, United Kingdom, G81 4HX
        • Golden Jubilee National Hospital
      • London, United Kingdom
        • St Georges Healthcare NHS Trust
      • Oxford, United Kingdom
        • Oxford University Hospitals NHS Trust
    • Leicestershire
      • Leicester, Leicestershire, United Kingdom, LE3 9QP
        • Glenfield Hospital
    • West Yorkshire
      • Leeds, West Yorkshire, United Kingdom, LS1 3EX
        • Leeds Teaching Hospitals NHS Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patient ≥30yrs
  • Patient has suspected stable angina (CHD) that requires further investigation
  • Has a defined risk of 10-90% (according to NICE guidelines CG95; 2010)
  • Suitable for revascularisation if required
  • Given informed written consent

Exclusion Criteria:

  • Non-anginal chest pain
  • Clinically unstable
  • Previous MI or biomarker positive ACS
  • Previous revascularisation with coronary artery bypass surgery or PCI
  • Contraindication to CMR imaging (pacemaker, intra-orbital debris, intra-auricular implants, intracranial clips, severe claustrophobia)
  • Contraindication to adenosine infusion (regular adenosine antagonist medication, significant reversible airways disease, second or third degree atrio-ventricular heart block, sino-atrial disease)
  • Known adverse reaction to Adenosine or Gadolinium contrast agent
  • Obesity (where body girth exceeds scanner diameter)
  • Pregnancy or breast feeding
  • Inability to give informed consent
  • Known chronic renal failure (eGFR <30mL/min/1.73m2)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: DIAGNOSTIC
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 3T CMR-guided management
Patient to be managed according to the results of 3T CMR imaging
Other: 3T CMR
3Tesla Cardiac Magnetic Resonance Imaging
Other: X-Ray coronary angiography
X-Ray coronary angiography
Active Comparator: SPECT-guided management
Patients to be managed according to the results of SPECT
Other: X-Ray coronary angiography
X-Ray coronary angiography
Other: SPECT
SPECT: Single Photon Emission Computed Tomography
Active Comparator: NICE-guidelines based management

Patients will be receive NICE-guidelines based management and will receive the imaging strategy specified by NICE according to their pre-test likelihood of having CHD.

10-29% - CT calcium score +/- CT coronary angiography; 30-60% - SPECT; 61-90% - X-Ray coronary angiography
Other: X-Ray coronary angiography
X-Ray coronary angiography
Other: SPECT
SPECT: Single Photon Emission Computed Tomography
Other: CT calcium score
CT calcium score
Other: CT coronary angiography
CT coronary angiography

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Unnecessary Invasive Coronary Angiography
Time Frame: 12 months
  • A negative FFR and positive non-invasive test (either 3T CMR or SPECT/CCT)
  • A negative FFR in a high pre-test risk (61-90%) patient that proceeds directly to invasive angiography in the NICE guidelines-based strategy arm
  • A negative FFR and a negative non-invasive test (either 3T CMR or SPECT/CCT) (i.e. a True Negative strategy result in which the imaging result was 'not believed' by the treating cardiologist)
  • An inconclusive non-invasive test result (either 3T CMR or SPECT/CCT) in which angiography had to be performed to make the diagnosis
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Major Adverse Cardiovascular Event (MACE)
Time Frame: at 12 months

MACE is defined as one of the following:

  • Death due to cardiovascular cause (including type 3 MI) †
  • Myocardial infarction†
  • Unplanned revascularisation
  • Hospital admission for cardiovascular cause [ACS Troponin -ve, spontaneous myocardial infarction (Type 1)†, Myocardial infarction secondary to ischaemic imbalance (Type 2) †, Myocardial Infarction related to stent thrombosis (Type 4b) †, Arrhythmia, Stroke, Heart failure]. † As defined by the third universal definition of myocardial infarction.
at 12 months
Positive Angiogram (by FFR) Rate for Each Strategy.
Time Frame: 12 months
The Positive Angiogram rate will be determined from the proportion of patients in the relevant population who undergo an angiogram within 12 months of randomisation which yields a positive finding by FFR (or QCA where no FFR reading is undertaken)
12 months
Cost Effectiveness Analysis
Time Frame: 3 years
To assess the long term cost-effectiveness of the alternate diagnostic testing strategies, information from the trial will be used to update the economic model developed as part of the original CE-MARC trial. The model will use information from the trial, including on resource use, costs, HRQoL and other clinical outcomes (e.g. on unnecessary tests and MACE events), together with epidemiological, clinical and economic data from other sources to calculate costs and quality-adjusted life-years (QALYs) for patients. The economic analysis will use methods consistent with those recommended by the National Institute for Health and Clinical Excellence (NICE). Given the potential difference between diagnostic strategies in terms of mortality, the modelling will adopt a lifetime time horizon to capture any difference.
3 years
Health-related Quality-of-life Measures (SAQ-UK; SF12; EQ-5D)
Time Frame: 3 years

Health-related quality-of-life (HRQoL) will be measured at baseline (in clinic), 6 months, 12 months, 2yrs and 3yrs (by post), using the following validated questionnaires:

  • Seattle Angina Questionnaire (SAQ) - UK version
  • SF12v2
  • EuroQol (EQ-5D)
3 years
Complications
Time Frame: 3 years
Complications - investigational or procedural related only. All complications from all study procedures/investigations will be recorded and reported if they result in an extended length of stay or specific treatment.
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Leeds

Collaborators

British Heart Foundation
University of Leicester
University of Glasgow

Investigators

  • Principal Investigator: John P Greenwood, PhD, University of Leeds

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2012

Primary Completion (Actual)

March 1, 2016

Study Completion (Actual)

March 1, 2018

Study Registration Dates

First Submitted

August 10, 2012

First Submitted That Met QC Criteria

August 13, 2012

First Posted (Estimate)

August 14, 2012

Study Record Updates

Last Update Posted (Actual)

November 23, 2018

Last Update Submitted That Met QC Criteria

May 1, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SP/12/1/29062

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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