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Coronary Heart DiseaseCE-MARC2NCT01664858

Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease-2

A study testing 3T CMR, SPECT and CT calcium score in people with Coronary Heart Disease, run by University of Leeds at 6 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 30 years and older
Conditions the study is for
Coronary Heart Disease
What is being tested?
3T CMR, SPECT and CT calcium score
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,202 participants
Where
6 sitesUnited Kingdom
Study dates
Nov 2012to Mar 2018
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 30 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)
Show all 11Show fewer
  • 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)

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United Kingdom6 sites
  • University Hospitals Bristol NHS FT

    Bristol

  • Golden Jubilee National Hospital

    Glasgow, G81 4HX

  • Leeds Teaching Hospitals NHS Trust

    Leeds, West Yorkshire, LS1 3EX

  • Glenfield Hospital

    Leicester, Leicestershire, LE3 9QP

  • St Georges Healthcare NHS Trust

    London

  • Oxford University Hospitals NHS Trust

    Oxford

Other trials in United Kingdom

About this study

Official title: 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.

Read the 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.

Being tested
3T CMR, SPECT, CT calcium score, CT coronary angiography, X-Ray coronary angiography
Keywords
Coronary Heart Disease, Ischaemic Heart Disease, Angina, Cardiac Magnetic Resonance Imaging
Medical subject headings
Coronary Disease, Coronary Artery Disease, Angina Pectoris

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 3T CMROther

    3Tesla Cardiac Magnetic Resonance Imaging

  • SPECTOther

    SPECT: Single Photon Emission Computed Tomography

  • CT calcium scoreOther

    CT calcium score

  • CT coronary angiographyOther

    CT coronary angiography

  • X-Ray coronary angiographyOther

    X-Ray coronary angiography

Study groups in NCT01664858
Study groupRoleWhat they receive
3T CMR-guided managementActive comparatorPatient to be managed according to the results of 3T CMR imaging
Receives: Other: 3T CMR; Other: X-Ray coronary angiography
SPECT-guided managementActive comparatorPatients to be managed according to the results of SPECT
Receives: Other: SPECT; Other: X-Ray coronary angiography
NICE-guidelines based managementActive comparatorPatients 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
Receives: Other: SPECT; Other: CT calcium score; Other: CT coronary angiography; Other: X-Ray coronary angiography

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Unnecessary Invasive Coronary Angiography

    • 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

    Measured: 12 months

Secondary outcomes (5)
  1. Major Adverse Cardiovascular Event (MACE)

    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.

    Measured: at 12 months

  2. Positive Angiogram (by FFR) Rate for Each Strategy.

    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)

    Measured: 12 months

  3. Cost Effectiveness Analysis

    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.

    Measured: 3 years

  4. Health-related Quality-of-life Measures (SAQ-UK; SF12; EQ-5D)

    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)

    Measured: 3 years

  5. Complications

    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.

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Aug 2012 (estimated)
  2. Study startNov 2012
  3. Primary completionMar 2016
  4. Study completionMar 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Diagnosis
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1,202 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01664858
Sponsor's protocol ID
SP/12/1/29062
Acronym
CE-MARC2
Status last verified
May 2018
First submitted
10 Aug 2012
Last updated
23 Nov 2018
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Ripley DP, Brown JM, Everett CC, Bijsterveld P, Walker S, Sculpher M, McCann GP, Berry C, Plein S, Greenwood JP. Rationale and design of the Clinical Evaluation of Magnetic Resonance Imaging in Coronary heart disease 2 trial (CE-MARC 2): a prospective, multicenter, randomized trial of diagnostic strategies in suspected coronary heart disease. Am Heart J. 2015 Jan;169(1):17-24.e1. doi: 10.1016/j.ahj.2014.10.008. Epub 2014 Oct 22.

    PubMed 25497243
  • Greenwood JP, Ripley DP, Berry C, McCann GP, Plein S, Bucciarelli-Ducci C, Dall'Armellina E, Prasad A, Bijsterveld P, Foley JR, Mangion K, Sculpher M, Walker S, Everett CC, Cairns DA, Sharples LD, Brown JM; CE-MARC 2 Investigators. Effect of Care Guided by Cardiovascular Magnetic Resonance, Myocardial Perfusion Scintigraphy, or NICE Guidelines on Subsequent Unnecessary Angiography Rates: The CE-MARC 2 Randomized Clinical Trial. JAMA. 2016 Sep 13;316(10):1051-60. doi: 10.1001/jama.2016.12680.

    PubMed 27570866
  • Everett CC, Berry C, McCann GP, Fernandez C, Reynolds C, Bucciarelli-Ducci C, Dall'Armellina E, Prasad A, Foley JR, Mangion K, Bijsterveld P, Brown J, Stocken D, Walker S, Sculpher M, Plein S, Greenwood JP. Randomised trial of stable chest pain investigation: 3-year clinical and quality of life results from CE-MARC 2. Open Heart. 2023 May;10(1):e002221. doi: 10.1136/openhrt-2022-002221.

    PubMed 37130657
  • Corcoran D, Young R, Adlam D, McConnachie A, Mangion K, Ripley D, Cairns D, Brown J, Bucciarelli-Ducci C, Baumbach A, Kharbanda R, Oldroyd KG, McCann GP, Greenwood JP, Berry C. Coronary microvascular dysfunction in patients with stable coronary artery disease: The CE-MARC 2 coronary physiology sub-study. Int J Cardiol. 2018 Sep 1;266:7-14. doi: 10.1016/j.ijcard.2018.04.061. Epub 2018 Apr 19.

    PubMed 29716756

Questions about this trial

What is this clinical trial studying?

A study testing 3T CMR, SPECT and CT calcium score in people with Coronary Heart Disease, run by University of Leeds at 6 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Unnecessary Invasive Coronary Angiography (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01664858, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Nov 2018.

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