Clinical trial NCT01664858: Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease-2
Official title: Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease - 2 (CE-MARC2)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Coronary Heart Disease
Keywords: Coronary Heart Disease
Ischaemic Heart Disease
Angina
Cardiac Magnetic Resonance Imaging
Lead sponsor: University of Leeds
Sponsor class: OTHER
Collaborators: name: University of Leicester
name: University of Glasgow
name: British Heart Foundation
First posted: 2012-08-14
Enrollment: 1202
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Number of Participants With Unnecessary Invasive Coronary Angiography
timeFrame: 12 months
Secondary outcomes:
measure: Major Adverse Cardiovascular Event (MACE)
timeFrame: at 12 months
measure: Positive Angiogram (by FFR) Rate for Each Strategy.
timeFrame: 12 months
measure: Cost Effectiveness Analysis
timeFrame: 3 years
measure: Health-related Quality-of-life Measures (SAQ-UK; SF12; EQ-5D)
timeFrame: 3 years
measure: Complications
timeFrame: 3 years
Other outcomes:
Locations:
city: Leicester
country: United Kingdom
facility: Glenfield Hospital
state: Leicestershire
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
state: West Yorkshire
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol NHS FT
city: Glasgow
country: United Kingdom
facility: Golden Jubilee National Hospital
city: London
country: United Kingdom
facility: St Georges Healthcare NHS Trust
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Trust
Study officials:
affiliation: University of Leeds
name: John P Greenwood, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
citation: 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.