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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University of Leeds
Sponsor:
Collaborators:
University of Leicester
University of Glasgow
British Heart Foundation
Information provided by (Responsible Party):
Professor JP Greenwood, University of Leeds
ClinicalTrials.gov Identifier:
NCT01664858
First received: August 10, 2012
Last updated: August 6, 2014
Last verified: August 2014

August 10, 2012
August 6, 2014
November 2012
September 2016   (final data collection date for primary outcome measure)
Unnecessary invasive coronary angiography [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • 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
Same as current
Complete list of historical versions of study NCT01664858 on ClinicalTrials.gov Archive Site
  • Major adverse cardiovascular event (MACE) [ Time Frame: at 12 months and at 3 years ] [ Designated as safety issue: Yes ]

    MACE is defined as one of the following:

    • Death due to Cardiovascular causes,
    • Myocardial infarction,
    • Unscheduled revascularisation,
    • Hospital admission for cardiovascular cause
    • Myocardial Infarction (STEMI)
    • ACS Troponin +ve (i.e. NSTEMI)
    • ACS Troponin -ve
    • Arrhythmia
    • Stroke
    • Heart failure
  • False Negative and True Positive rates for each strategy. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    False Negative (i.e. negative non-invasive test and positive FFR (≤0.80) and True Positive (i.e. positive non-invasive test and positive FFR (≤0.80)) rates for each strategy.
  • Cost effectiveness analysis [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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.
  • Health-related quality-of-life measures (SAQ-UK; SF12; EQ-5D) [ Time Frame: 3 years ] [ Designated as safety issue: No ]

    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)
  • Complications [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    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.
  • Major adverse cardiovascular event (MACE) [ Time Frame: at 12 months and at 3 years ] [ Designated as safety issue: Yes ]

    MACE is defined as one of the following:

    • Death due to Cardiovascular causes,
    • Myocardial infarction,
    • Unscheduled revascularisation,
    • Hospital admission for cardiovascular cause
    • Myocardial Infarction (STEMI)
    • ACS Troponin +ve (i.e. NSTEMI)
    • ACS Troponin -ve
    • Arrhythmia
    • Stroke
    • Heart failure
  • False Negative and True Positive rates for each strategy. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    False Negative (i.e. negative non-invasive test and positive FFR (≤0.80) and True Positive (i.e. positive non-invasive test and positive FFR (≤0.80)) rates for each strategy.
  • Cost effectiveness analysis [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Cost effectiveness analysis
  • Health-related quality-of-life measures (SAQ-UK; SF12; EQ-5D) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Health-related quality-of-life measures (SAQ-UK; SF12; EQ-5D)
  • Complications [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    Complications - investigational or procedural related only
Not Provided
Not Provided
 
Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease-2
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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Coronary Heart Disease
  • Other: 3T CMR
    3Tesla Cardiac Magnetic Resonance Imaging
  • Other: SPECT
    SPECT: Single Photon Emission Computed Tomography
  • Other: CT calcium score
    CT calcium score
  • Other: CT coronary angiography
    CT coronary angiography
  • Other: X-Ray coronary angiography
    X-Ray coronary angiography
  • Active Comparator: 3T CMR-guided management
    Patient to be managed according to the results of 3T CMR imaging
    Interventions:
    • Other: 3T CMR
    • Other: X-Ray coronary angiography
  • Active Comparator: SPECT-guided management
    Patients to be managed according to the results of SPECT
    Interventions:
    • Other: SPECT
    • Other: X-Ray coronary angiography
  • 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

    Interventions:
    • Other: SPECT
    • Other: CT calcium score
    • Other: CT coronary angiography
    • Other: X-Ray coronary angiography
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
1200
September 2018
September 2016   (final data collection date for primary outcome measure)

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)
Both
30 Years and older
No
Contact: Petra Bijsterveld, MA, RGN +44(0)1133925481 p.bijsterveld@leeds.ac.uk
United Kingdom
 
NCT01664858
SP/12/1/29062
Yes
Professor JP Greenwood, University of Leeds
University of Leeds
  • University of Leicester
  • University of Glasgow
  • British Heart Foundation
Principal Investigator: John P Greenwood, PhD University of Leeds
University of Leeds
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP