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

Tracking Information
First Submitted Date ICMJE	August 10, 2012
First Posted Date ICMJE	August 14, 2012
Last Update Posted Date	March 30, 2015
Study Start Date ICMJE	November 2012
Estimated Primary Completion Date	March 2016 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: August 13, 2012)	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
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01664858 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: October 7, 2014)	Major adverse cardiovascular event (MACE) [ Time Frame: at 12 months and at 3 years ]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.; 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); 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.; 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); 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.
Original Secondary Outcome Measures ICMJE; (submitted: August 13, 2012)	Major adverse cardiovascular event (MACE) [ Time Frame: at 12 months and at 3 years ]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 ]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 ]Cost effectiveness analysis; Health-related quality-of-life measures (SAQ-UK; SF12; EQ-5D) [ Time Frame: 3 years ]Health-related quality-of-life measures (SAQ-UK; SF12; EQ-5D); Complications [ Time Frame: 3 years ]Complications - investigational or procedural related only
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease-2
Official Title ICMJE	Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease - 2 (CE-MARC2)
Brief 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 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.
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 ICMJE	Interventional
Study Phase	Phase 4
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic
Condition ICMJE	Coronary Heart Disease
Intervention ICMJE	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
Study Arms	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
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.; 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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Unknown status
Estimated Enrollment ICMJE; (submitted: August 13, 2012)	1200
Original Estimated Enrollment ICMJE	Same as current
Estimated Study Completion Date	March 2018
Estimated Primary Completion Date	March 2016 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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)
Sex/Gender	Sexes Eligible for Study: All
Ages	30 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United Kingdom
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01664858
Other Study ID Numbers ICMJE	SP/12/1/29062
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Professor JP Greenwood, University of Leeds
Study Sponsor ICMJE	University of Leeds
Collaborators ICMJE	University of Leicester; University of Glasgow; British Heart Foundation
Investigators ICMJE	Principal Investigator: John P Greenwood, PhD University of Leeds
PRS Account	University of Leeds
Verification Date	March 2015
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP