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

Coronary Heart Disease Clinical Trial

— CE-MARC2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01664858
• Other study ID #: SP/12/1/29062
• Status: Completed
• Phase: N/A
• Start date: November 2012
• Est. completion date: March 2018

Study information

• Verified date: May 2018
• Source: University of Leeds
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1202
• Est. completion date: March 2018
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Coronary Heart Disease
• Heart Diseases
• Myocardial Ischemia

Intervention

Other:
• 3T CMR
3Tesla Cardiac Magnetic Resonance Imaging
• SPECT
SPECT: Single Photon Emission Computed Tomography
• CT calcium score
CT calcium score
• CT coronary angiography
CT coronary angiography
• X-Ray coronary angiography
X-Ray coronary angiography

Locations

Country	Name	City	State
United Kingdom	University Hospitals Bristol NHS FT	Bristol
United Kingdom	Golden Jubilee National Hospital	Glasgow
United Kingdom	Leeds Teaching Hospitals NHS Trust	Leeds	West Yorkshire
United Kingdom	Glenfield Hospital	Leicester	Leicestershire
United Kingdom	St Georges Healthcare NHS Trust	London
United Kingdom	Oxford University Hospitals NHS Trust	Oxford

Sponsors (4)

Lead Sponsor	Collaborator
University of Leeds	British Heart Foundation, University of Glasgow, University of Leicester

Country where clinical trial is conducted

United Kingdom, 

References & Publications (2)

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 b — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	12 months
Secondary	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.	at 12 months
Secondary	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)	12 months
Secondary	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.	3 years
Secondary	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)	3 years
Secondary	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.	3 years

External Links

•   Leeds CMR clinical research group website