Microvascular AnginaCorCMRNCT04805814
Coronary Microvascular Angina Cardiac Magnetic Resonance Imaging (CorCMR) Trial
A study testing CMR results disclosed and CMR performed but results not disclosed in people with Microvascular Angina and Angina Pectoris, run by NHS National Waiting Times Centre Board at 3 sites in United Kingdom.
Trial summary
Anginal symptoms due to ischaemia with no obstructive coronary arteries (INOCA) is a common clinical problem, however, diagnosis and onward management is heterogeneous, and prognosis is affected. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Microvascular Angina, Angina Pectoris, Angina, Stable
- What is being tested?
- CMR results disclosed and CMR performed but results not disclosed
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 280 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- 9 Feb 2021to 1 Oct 2034
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years
- Symptoms of angina or angina-equivalent informed by the Rose Angina questionnaire.
- Coronary angiography ≤3 months with a plan for medical management.
Who cannot join
- Obstructive coronary artery disease i.e. a stenosis >70% in a single segment or 50 - 70% in 2 adjacent segments in an artery >2.5 mm, or FFR ≤0.80.
- Coronary revascularization by percutaneous coronary intervention or coronary artery bypass graft surgery following the index angiogram.
- Prior coronary artery bypass surgery
- A diagnosis that would explain the angina e.g. anaemia, aortic stenosis, hypertrophic cardiomyopathy,
- Contra-indication to contrast-enhanced CMR e.g. eGFR < 30mL/min/1.73m2.
- Contra-indication to intravenous adenosine, i.e. severe asthma; long QT syndrome; second- or third-degree AV block and sick sinus syndrome.
- Lack of informed consent.
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
University Hospital Ayr
Ayr, Scotland, KA6 6D
University Hospital Hairmyres
East Kilbride, Glasgow, G75 8RG
Golden Jubilee National Hospital
Glasgow, Scotland, G81 4DY
About this study
Official title: The Clinical Utility Of Cardiac Magnetic Resonance Imaging in Patients With Angina But No Obstructive Coronary Disease (CorCMR): A Diagnostic Study And Nested Randomised Trial
Anginal symptoms due to ischaemia with no obstructive coronary arteries (INOCA) is a common clinical problem, however, diagnosis and onward management is heterogeneous, and prognosis is affected. Recent advances in quantifying myocardial blood flow using stress perfusion cardiac magnetic resonance imaging (CMR) has potential for accurate detection coronary microvascular dysfunction.
The CorCMR diagnostic study involves stress perfusion CMR in patients with suspected INOCA to clarify the prevalence of subgroups of patients with underlying problems, such as microvascular disease or undisclosed obstructive coronary artery disease, that might explain their anginal symptoms.
A nested, prospective, randomised, controlled, double-blind trial will determine whether stratified medical therapy guided by the results of the stress perfusion CMR improves symptoms, well-being, cardiovascular risk and health and economic outcomes.
Read the detailed description
Background:
There are approximately 2 million men and women living with angina in the UK. In 2014, there were ~247,000 coronary angiograms performed, mostly for the investigation of known or suspected angina. However, obstructive CAD is detected in only 1 in 2 patients. The explanation for the cause(s) of the chest pain are often unclear. Microvascular or vasospastic angina may be one explanation.
Adjunctive tests of coronary artery function to diagnose these problems are rarely used during coronary angiography in the NHS, meaning that patient management may be empirical and heterogeneous. The lack of adoption of these novel tests in the NHS reflects key gaps in the clinical evidence. It is these gaps, coupled with the increasing adoption of anatomical coronary artery imaging with CT coronary angiography (CTCA), which stimulate this research. In recent large clinical trials, CT coronary angiography has been shown not to reduce the rate of invasive angiography. In fact, compared to standard care based on stress testing, CTCA is associated with less improvement in anginal symptoms and in quality of life (PUBMED ID: 28246175). Anatomical tests, such as CTCA and invasive angiography, do not provide information on myocardial blood flow. New evidence that addresses these gaps might inform therapy development and future trials.
Current gaps in evidence and guidelines point to a problem of unmet need in the NHS care pathway. Stress perfusion CMR has potential diagnostic value for microvascular disease, but whether it might discriminate clinical endotypes in a relatively unselected population of patients in daily practice, is uncertain. Further, access to stress perfusion CMR varies widely not least because evidence from randomised trials supporting clinical and economic benefits from a CMR-guided approach is lacking. CorCMR is a clinical strategy trial that is designed to address this evidence gap.
Hypothesis:
In patients with angina in whom obstructive disease in the epicardial coronary arteries has been ruled out by coronary angiography ± FFR, stress perfusion CMR will reclassify the diagnosis leading to changes in treatment (start or stop therapy), improvements in health and economic outcomes, as compared to decisions based standard care (CMR not disclosed).
Design:
We propose that an observational, diagnostic study involving stress CMR will provide information on the prevalence of microvascular disease in a population with anginal symptoms potentially attributable to myocardial ischaemia with no obstructive coronary arteries (INOCA). Each diagnosis is linked to a guideline-directed treatment plan.The potential value of this strategy can only be confirmed if it is associated with patient benefits, which is why we propose a nested, randomised, controlled, double-blind trial of routine disclosure of stress perfusion CMR vs. angiography-guided management
Methods:
Patients undergoing invasive coronary angiography for the investigation of known or suspected angina and who do not have either structural heart disease or a systemic health problem that would explain those symptoms will be invited to participate. Written informed consent is required for participation. Eligibility is further confirmed at the time of the coronary angiogram by exclusion of obstructive (stenosis >70% in a single segment or 50 - 70% in 2 adjacent segments in an artery >2.5 mm, or FFR ≤0.80) coronary artery disease (CAD). Angina symptoms will be confirmed by the completion of validated questionnaires and patients will be invited to attend for a stress perfusion CMR within 3 months of the original coronary angiogram.
On arrival for the CMR, patients will be randomised (1:1) to either the intervention (CMR guided, results disclosed) or blinded control group (CMR undertaken but results not disclosed, standard of care) group.
Trial participants will be blinded to treatment group. The clinicians responsible for on-going care will also be blinded. The design is therefore 'double-blind'. Following the CMR, patients and clinicians will be advised of the diagnosis (endotype) but not the randomised group. The endotype will be informed by the CMR in the intervention group but not in the control group (CMR results not disclosed, angiography-guided). Medical therapy and lifestyle measures are linked to the endotype and informed by contemporary practice guidelines. Therefore, optimal guideline-directed medical care according to the endotype is intended to be the same, regardless of the group allocation.
The sample size is 280 randomised participants. The minimum follow-up duration is 12 months from the last participant recruitment. Follow-up will continued in the longer term including, where feasible, electronic case record linkage.
The primary outcome of the diagnostic study is the reclassification of the initial diagnosis based on findings from the cardiac MRI scan. The primary outcome of the nested randomised trial is the within-subject change at 6 months from baseline for the domains of the Seattle Angina Questionnaire.
Secondary outcomes include other Patient Reported Outcome Measures (PROMS) to describe other aspects of health and wellbeing. These include EQ-5D-5L, Illness perception (Brief IPQ), Treatment satisfaction (TSQM), Duke Activity Status Index (DASI), the International Physical Activity Questionnaire (IPAQ-SF) short-form and a pain questionnaire.
There is preliminary evidence that small vessel disease can be a systemic problem affecting different organs. Whether small vessel disease in the heart might associate with small vessel disease in the brain or retina is unknown. In the CorMicA pilot study, studies of small vessels isolated from biopsies found evidence of endothelial dysfunction and increased responsiveness of the blood vessels to naturally-occurring, constriction-inducing peptides such as endothelin and thromboxane. For these reasons, we plan heart-brain-retina and peripheral vascular substudies.
- Conditions
- Microvascular Angina, Angina Pectoris, Angina, Stable, Non-Obstructive Coronary Atherosclerosis, Small Vessel Cerebrovascular Disease, Coronary Artery Disease
- Being tested
- CMR results disclosed, CMR performed but results not disclosed
- Medical subject headings
- Microvascular Angina, Angina Pectoris, Angina, Stable, Cerebral Small Vessel Diseases, Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CMR results disclosedDiagnostic test
The results of the CMR are disclosed, and used to guide management
CMR performed but results not disclosedDiagnostic test
The results of the CMR are not disclosed, and management is angiography-guided
| Study group | Role | What they receive |
|---|---|---|
| Intervention Group | Active comparator | All randomised participants will receive stratified medicine. The subjects will undergo stress perfusion CMR as an adjunct to invasive coronary angiography. The CMR results will be disclosed to the clinician to clarify endotypes and re-evaluate the clinical diagnosis. Linked guideline-directed medical therapy and lifestyle measures will be recommended based on the endotype. The patient and clinicians responsible for downstream care will not be informed of the randomised group but they will be informed of the endotype and linked treatment plan, in the same way as in the Standard Care control group. They will be blinded to the allocated study arm and CMR findings. Receives: Diagnostic Test: CMR results disclosed |
| Standard Care Group | Sham comparator | All randomised participants in this arm will receive standard angiography-guided care. The endotype will be determined based on the angiogram and all of the available clinical information. The participants in this group will also undergo stress perfusion CMR but the results will not be disclosed. Management of the patient is as per standard of care, with therapy linked to the diagnosis (endotype). The patient and clinicians responsible for downstream care will not be informed of the randomised group but they will be informed of the endotype and linked treatment plan in the same way as in the Intervention Group. They will be blinded to the allocated study arm and CMR findings. Receives: Diagnostic Test: CMR performed but results not disclosed |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reclassification of the initial diagnosis
The reclassification of the initial diagnosis based on invasive management following multi-parametric stress perfusion CMR. The diagnostic groups (endotypes) are:
- Anginal symptoms with a myocardial perfusion defect indicative of obstructive CAD;
- Anginal symptoms associated with a myocardial perfusion defect indicative of microvascular disease;
- Vasospastic angina;
- Incidental finding that is actionable e.g. aortic stenosis, cardiomyopathy, lung cancer; or
- No clinically significant finding or normal.
Measured: Day 1
Seattle Angina Questionnaire (SAQ) Summary Score
The 7-item version of the SAQ reflects the frequency of angina (SAQ Angina Frequency score) and the disease-specific effect of angina on patients' physical function (SAQ Physical Limitation score) and quality of life (Quality of Life score) over the previous 4 weeks; these scores are averaged to obtain the SAQ Summary score, which is an overall measure of patients' stable ischaemic heart disease-specific health status. SAQ scores range from 0 to 100, with higher scores indicating less frequent angina, improved function, and better quality of life.
Measured: 6 months
Secondary outcomes (27)
Compliance with the protocol
Assess feasibility of the clinical strategy by measuring compliance with the protocol and, specifically, rate of enrolment, % of patients who drop-out, % of patients who complete the diagnostic MRI protocol.
Measured: 0-36 months
Integrity of blinding in the Radiology Department and during follow-up
Assess the integrity and feasibility of blinding by administering patient and clinician questionnaires to determine if both groups have been successfully blinded
Measured: 0-36 months
Diagnostic utility
To assess % of patients with a change in diagnosis following disclosure of the cardiac MRI results, and relatedly, the level of certainty reported by the physicians for the diagnosis (diagnostic utility). This will be assessed by a questionnaire completed by the clinician before the MRI, and then again after the MRI results are disclosed.
Measured: 0-36 months
Clinical Utility
To assess impact of disclosure of the cardiac MRI results on clinical management (including treatment and investigations). This will be measured by asking clinicians to complete a questionnaire on ongoing clinical management following disclosure of the MRI result
Measured: 0-36 months
Abnormal myocardial perfusion
Assess the prevalence of abnormal blood flow in the heart muscle, as defined by a minimum of 2 adjacent cardiac segments each with ≥50% deficit in myocardial perfusion at peak stress revealed by (1) visual assessment of the dynamic stress perfusion CMR scan and (2) pixel mapping of myocardial blood flow (< 2.0 ml/min/g tissue).
Measured: Day 1
Myocardial blood flow
Assess the associations between myocardial blood flow (ml/min/g) and invasive measures of coronary function (where available) that might be implicated in the pathophysiology of abnormal coronary vascular function.
Measured: Day 1
Myocardial tissue characteristics
Assess the correlation between myocardial blood flow (ml/min/g) and myocardial tissue characteristics as revealed by MRI T1- and T2- relaxation times (ms) and extracellular volume fraction.
Measured: Day 1
Cardiovascular risk
Assess the correlation between cardiovascular risk factors, reflected by validated risk scores (e.g. ASSIGN, JBS3), and myocardial blood flow (ml/min/g) in medically managed patients.
Measured: Day 1
Within subject change in myocardial blood flow
Assess the within-subject change in cardiac MRI findings during 12-months. This will be done by measuring the within-subject change in peak, global, myocardial blood flow over 12 months.
Measured: 0-12 months
Between-group, within subject change in myocardial blood flow
Assess the between-group, within-subject change in cardiac MRI findings over 12 months. This outcome will provide insights into the effect of the study intervention on MRI findings. This will be done by measuring the within-subject, between group change in peak, global, myocardial blood flow over 12 months.
Measured: 0-12 months
Health Status: EQ5D-5L Questionnaire
The 5-item EuroQol Group EQ5D-5L is a validated questionnaire comprising mobility, self-care, usual activities, pain/discomfort and anxiety/depression to quantitatively assess patient's self-reported health status and will be administered at each study visit.
Measured: 0-36 months
Health Status: Seattle Angina Questionnaire
Seattle Angina Questionnaire (SAQ) Summary Score and component scores (Angina Limitation, Angina Stability, Angina Frequency, Treatment Satisfaction and Quality of Life) will be recorded at all study visits.
Measured: 0-36 months
Health Status: Illness Perception - Brief IPQ
Brief Illness Perception Questionnaire (Brief IPQ), a nine-item scale designed to rapidly assess the cognitive and emotional representations of illness taken at all study visits.
Measured: 0-36 months
Health Status: Treatment satisfaction - TSQM
The 14-item Treatment Satisfaction Questionnaire for Medication (TSQM) is a reliable and valid instrument to assess patients' satisfaction with medication, providing scores on four scales - side effects, effectiveness, convenience and global satisfaction and will administered at all study visits.
Measured: 0-36 months
Health Status: Duke Activity Status Index
The 12 point Duke Activity Status Index (DASI) is a validated questionnaire to assess functional capacity and will be administered at all study visits.
Measured: 0-36 months
Health Status: International Physical Activity Questionnaire- Short Form (IPAQ-SF)
The 4 point IPAQ-SF is a validated questionnaire to assess functional ability and activuty levels and will be administered at all study visits.
Measured: 0-36 months
Health Status: Montreal Cognitive Assessment (MOCA)
The MOCA is an internationally validated 30 point assessment of cognitive function, and will be administered on all study visits.
Measured: 0-36 months
Correlation between myocardial blood flow and health status
Assess the correlation between myocardial blood flow (ml/min/g) and health status, as measured by validated questionnaires.
Measured: 0-36 months
Long term prognosis
Assess the long-term prognostic significance of between myocardial perfusion (ml/min/g).
Measured: 0-20 years
Health Outcomes: Major Adverse Cardiovascular Events
MACE including death, re-hospitalisation for cardiovascular events including myocardial infarction, heart failure, stroke/ TIA, unstable angina and coronary revascularisation. Unscheduled hospital visits for chest pain that have not led to hospital admission will also be documented.
Measured: 0-20 years
Angina events
Anginal episodes based on completion of a chest symptoms log and adjudicated by a clinical event committee.
Measured: 0-3 years
Brain small vessel disease
Quantify small vessel disease score in the brain using the The STandards for ReportIng Vascular changes on nEuroimaging (STRIVE) guidelines.
Measured: 0-36 months
Correlation between small vessel disease in the brain and myocardial perfusion
Assess the correlation between MRI features of small vessel disease in the brain and myocardial perfusion.
Measured: 0-36 months
Health economics: Inpatients visits
Health resource utilisation will also be assessed by recording the number of inpatient visits in the follow-up period
Measured: 0-20 years
Health economics: Cardiac procedures
Health resource utilisation will also be assessed by recording the number of repeat cardiac procedures performed in the follow up period
Measured: 0-20 years
Health economics: Medication use
Health resource utilisation will also be assessed by recording the medication used in the follow up period
Measured: 0-20 years
Work limitation
Use the 8-item Work limitation Questionnaire to estimate productivity loss and time lost from work, where appropriate.
Measured: 0-36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2021
- Study start9 Feb 2021
- Primary completion1 Oct 2024
- Study completion1 Oct 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Microvascular AnginaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 280 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NHS National Waiting Times Centre Board
- Sponsor type
- University, hospital or other
- Collaborators
- University of Glasgow, British Heart Foundation, Chief Scientist Office of the Scottish Government
- Responsible party
- Principal investigator, Colin Berry, NHS National Waiting Times Centre Board
- Investigators
- Colin Berry, MBChB, PhD, Principal investigator, Univerisity of Glasgow
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04805814
- Sponsor's protocol ID
- 281128
- Acronym
- CorCMR
- Status last verified
- Jan 2025
- First submitted
- 9 Mar 2021
- Last updated
- 30 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymised data may be shared based on a research agreement
Publications
Bradley CP, Berry C. Microvascular arterial disease of the brain and the heart: a shared pathogenesis. QJM. 2023 Oct 23;116(10):829-834. doi: 10.1093/qjmed/hcad158.
PubMed 37467080Bradley CP, Orchard V, McKinley G, Heggie R, Wu O, Good R, Watkins S, Lindsay M, Eteiba H, McGowan J, McGeoch R, Corcoran D, Kellman P, McConnachie A, Berry C. The coronary microvascular angina cardiovascular magnetic resonance imaging trial: Rationale and design. Am Heart J. 2023 Nov;265:213-224. doi: 10.1016/j.ahj.2023.08.067. Epub 2023 Aug 30.
PubMed 37657593Bradley C, Berry C. Definition and epidemiology of coronary microvascular disease. J Nucl Cardiol. 2022 Aug;29(4):1763-1775. doi: 10.1007/s12350-022-02974-x. Epub 2022 May 9.
PubMed 35534718Sidik NP, Stanley B, Sykes R, Morrow AJ, Bradley CP, McDermott M, Ford TJ, Roditi G, Hargreaves A, Stobo D, Adams J, Byrne J, Mahrous A, Young R, Carrick D, McGeoch R, Corcoran D, Lang NN, Heggie R, Wu O, McEntegart MB, McConnachie A, Berry C. Invasive Endotyping in Patients With Angina and No Obstructive Coronary Artery Disease: A Randomized Controlled Trial. Circulation. 2024 Jan 2;149(1):7-23. doi: 10.1161/CIRCULATIONAHA.123.064751. Epub 2023 Oct 5.
PubMed 37795617Ludman P on behalf of the British Cardiovascular Intervention Society (BCIS). BCIS Audit Returns for Adult Interventional Procedures (Jan - Dec 2016). October 2017. https://www.bcis.org.uk/resources/audit-results/
Williams MC, Hunter A, Shah A, Assi V, Lewis S, Mangion K, Berry C, Boon NA, Clark E, Flather M, Forbes J, McLean S, Roditi G, van Beek EJ, Timmis AD, Newby DE; Scottish COmputed Tomography of the HEART (SCOT-HEART) Trial Investigators. Symptoms and quality of life in patients with suspected angina undergoing CT coronary angiography: a randomised controlled trial. Heart. 2017 Jul;103(13):995-1001. doi: 10.1136/heartjnl-2016-310129. Epub 2017 Feb 28.
PubMed 28246175Ford TJ, Stanley B, Good R, Rocchiccioli P, McEntegart M, Watkins S, Eteiba H, Shaukat A, Lindsay M, Robertson K, Hood S, McGeoch R, McDade R, Yii E, Sidik N, McCartney P, Corcoran D, Collison D, Rush C, McConnachie A, Touyz RM, Oldroyd KG, Berry C. Stratified Medical Therapy Using Invasive Coronary Function Testing in Angina: The CorMicA Trial. J Am Coll Cardiol. 2018 Dec 11;72(23 Pt A):2841-2855. doi: 10.1016/j.jacc.2018.09.006. Epub 2018 Sep 25.
PubMed 30266608Ford TJ, Stanley B, Sidik N, Good R, Rocchiccioli P, McEntegart M, Watkins S, Eteiba H, Shaukat A, Lindsay M, Robertson K, Hood S, McGeoch R, McDade R, Yii E, McCartney P, Corcoran D, Collison D, Rush C, Sattar N, McConnachie A, Touyz RM, Oldroyd KG, Berry C. 1-Year Outcomes of Angina Management Guided by Invasive Coronary Function Testing (CorMicA). JACC Cardiovasc Interv. 2020 Jan 13;13(1):33-45. doi: 10.1016/j.jcin.2019.11.001. Epub 2019 Nov 11.
PubMed 31709984Kunadian V, Chieffo A, Camici PG, Berry C, Escaned J, Maas AHEM, Prescott E, Karam N, Appelman Y, Fraccaro C, Buchanan GL, Manzo-Silberman S, Al-Lamee R, Regar E, Lansky A, Abbott JD, Badimon L, Duncker DJ, Mehran R, Capodanno D, Baumbach A. An EAPCI Expert Consensus Document on Ischaemia with Non-Obstructive Coronary Arteries in Collaboration with European Society of Cardiology Working Group on Coronary Pathophysiology & Microcirculation Endorsed by Coronary Vasomotor Disorders International Study Group. EuroIntervention. 2021 Jan 20;16(13):1049-1069. doi: 10.4244/EIJY20M07_01.
PubMed 32624456Ford TJ, Berry C. Angina: contemporary diagnosis and management. Heart. 2020 Mar;106(5):387-398. doi: 10.1136/heartjnl-2018-314661. Epub 2020 Feb 12. No abstract available.
PubMed 32054665Corcoran D, Ford T, Hsu LY, Orchard V, Oldroyd KG, Arai AE, Berry C, on behalf of the CorMicA Investigators. The diagnostic utility of multiparametric CMR in patients with angina and non-obstructive coronary artery disease. Eur Heart J. 2020;
Kotecha T, Martinez-Naharro A, Boldrini M, Knight D, Hawkins P, Kalra S, Patel D, Coghlan G, Moon J, Plein S, Lockie T, Rakhit R, Patel N, Xue H, Kellman P, Fontana M. Automated Pixel-Wise Quantitative Myocardial Perfusion Mapping by CMR to Detect Obstructive Coronary Artery Disease and Coronary Microvascular Dysfunction: Validation Against Invasive Coronary Physiology. JACC Cardiovasc Imaging. 2019 Oct;12(10):1958-1969. doi: 10.1016/j.jcmg.2018.12.022. Epub 2019 Feb 13.
PubMed 30772231Hsu LY, Jacobs M, Benovoy M, Ta AD, Conn HM, Winkler S, Greve AM, Chen MY, Shanbhag SM, Bandettini WP, Arai AE. Diagnostic Performance of Fully Automated Pixel-Wise Quantitative Myocardial Perfusion Imaging by Cardiovascular Magnetic Resonance. JACC Cardiovasc Imaging. 2018 May;11(5):697-707. doi: 10.1016/j.jcmg.2018.01.005. Epub 2018 Feb 14.
PubMed 29454767Knott KD, Seraphim A, Augusto JB, Xue H, Chacko L, Aung N, Petersen SE, Cooper JA, Manisty C, Bhuva AN, Kotecha T, Bourantas CV, Davies RH, Brown LAE, Plein S, Fontana M, Kellman P, Moon JC. The Prognostic Significance of Quantitative Myocardial Perfusion: An Artificial Intelligence-Based Approach Using Perfusion Mapping. Circulation. 2020 Apr 21;141(16):1282-1291. doi: 10.1161/CIRCULATIONAHA.119.044666. Epub 2020 Feb 14.
PubMed 32078380Berry C, Sidik N, Pereira AC, Ford TJ, Touyz RM, Kaski JC, Hainsworth AH. Small-Vessel Disease in the Heart and Brain: Current Knowledge, Unmet Therapeutic Need, and Future Directions. J Am Heart Assoc. 2019 Feb 5;8(3):e011104. doi: 10.1161/JAHA.118.011104. No abstract available.
PubMed 30712442
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Clinical Utility Of Cardiac Magnetic Resonance Imaging in Patients With Angina But No Obstructive Coronary Disease (CorCMR): A Diagnostic Study And Nested Randomised Trial
- ClinicalTrials.gov ID
- NCT04805814
- Acronym / sponsor ID
- CorCMR / 281128
- Conditions
- Microvascular Angina, Angina Pectoris, Angina, Stable, Non-Obstructive Coronary Atherosclerosis, Small Vessel Cerebrovascular Disease, Coronary Artery Disease
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 280 participants (estimated)
- Lead sponsor
- NHS National Waiting Times Centre BoardUniversity, hospital or other
- Collaborators
- University of Glasgow, British Heart Foundation, Chief Scientist Office of the Scottish Government
- Study start
- 9 Feb 2021 (actual)
- Primary completion
- 1 Oct 2024 (actual)
- Study completion
- 1 Oct 2034 (estimated)
- First posted
- 18 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Anginal symptoms due to ischaemia with no obstructive coronary arteries (INOCA) is a common clinical problem, however, diagnosis and onward management is heterogeneous, and prognosis is affected. Recent advances in quantifying myocardial blood flow using stress perfusion cardiac magnetic resonance imaging (CMR) has potential for accurate detection coronary microvascular dysfunction.
The CorCMR diagnostic study involves stress perfusion CMR in patients with suspected INOCA to clarify the prevalence of subgroups of patients with underlying problems, such as microvascular disease or undisclosed obstructive coronary artery disease, that might explain their anginal symptoms.
A nested, prospective, randomised, controlled, double-blind trial will determine whether stratified medical therapy guided by the results of the stress perfusion CMR improves symptoms, well-being, cardiovascular risk and health and economic outcomes.
Detailed description
Background:
There are approximately 2 million men and women living with angina in the UK. In 2014, there were ~247,000 coronary angiograms performed, mostly for the investigation of known or suspected angina. However, obstructive CAD is detected in only 1 in 2 patients. The explanation for the cause(s) of the chest pain are often unclear. Microvascular or vasospastic angina may be one explanation.
Adjunctive tests of coronary artery function to diagnose these problems are rarely used during coronary angiography in the NHS, meaning that patient management may be empirical and heterogeneous. The lack of adoption of these novel tests in the NHS reflects key gaps in the clinical evidence. It is these gaps, coupled with the increasing adoption of anatomical coronary artery imaging with CT coronary angiography (CTCA), which stimulate this research. In recent large clinical trials, CT coronary angiography has been shown not to reduce the rate of invasive angiography. In fact, compared to standard care based on stress testing, CTCA is associated with less improvement in anginal symptoms and in quality of life (PUBMED ID: 28246175). Anatomical tests, such as CTCA and invasive angiography, do not provide information on myocardial blood flow. New evidence that addresses these gaps might inform therapy development and future trials.
Current gaps in evidence and guidelines point to a problem of unmet need in the NHS care pathway. Stress perfusion CMR has potential diagnostic value for microvascular disease, but whether it might discriminate clinical endotypes in a relatively unselected population of patients in daily practice, is uncertain. Further, access to stress perfusion CMR varies widely not least because evidence from randomised trials supporting clinical and economic benefits from a CMR-guided approach is lacking. CorCMR is a clinical strategy trial that is designed to address this evidence gap.
Hypothesis:
In patients with angina in whom obstructive disease in the epicardial coronary arteries has been ruled out by coronary angiography ± FFR, stress perfusion CMR will reclassify the diagnosis leading to changes in treatment (start or stop therapy), improvements in health and economic outcomes, as compared to decisions based standard care (CMR not disclosed).
Design:
We propose that an observational, diagnostic study involving stress CMR will provide information on the prevalence of microvascular disease in a population with anginal symptoms potentially attributable to myocardial ischaemia with no obstructive coronary arteries (INOCA). Each diagnosis is linked to a guideline-directed treatment plan.The potential value of this strategy can only be confirmed if it is associated with patient benefits, which is why we propose a nested, randomised, controlled, double-blind trial of routine disclosure of stress perfusion CMR vs. angiography-guided management
Methods:
Patients undergoing invasive coronary angiography for the investigation of known or suspected angina and who do not have either structural heart disease or a systemic health problem that would explain those symptoms will be invited to participate. Written informed consent is required for participation. Eligibility is further confirmed at the time of the coronary angiogram by exclusion of obstructive (stenosis >70% in a single segment or 50 - 70% in 2 adjacent segments in an artery >2.5 mm, or FFR ≤0.80) coronary artery disease (CAD). Angina symptoms will be confirmed by the completion of validated questionnaires and patients will be invited to attend for a stress perfusion CMR within 3 months of the original coronary angiogram.
On arrival for the CMR, patients will be randomised (1:1) to either the intervention (CMR guided, results disclosed) or blinded control group (CMR undertaken but results not disclosed, standard of care) group.
Trial participants will be blinded to treatment group. The clinicians responsible for on-going care will also be blinded. The design is therefore 'double-blind'. Following the CMR, patients and clinicians will be advised of the diagnosis (endotype) but not the randomised group. The endotype will be informed by the CMR in the intervention group but not in the control group (CMR results not disclosed, angiography-guided). Medical therapy and lifestyle measures are linked to the endotype and informed by contemporary practice guidelines. Therefore, optimal guideline-directed medical care according to the endotype is intended to be the same, regardless of the group allocation.
The sample size is 280 randomised participants. The minimum follow-up duration is 12 months from the last participant recruitment. Follow-up will continued in the longer term including, where feasible, electronic case record linkage.
The primary outcome of the diagnostic study is the reclassification of the initial diagnosis based on findings from the cardiac MRI scan. The primary outcome of the nested randomised trial is the within-subject change at 6 months from baseline for the domains of the Seattle Angina Questionnaire.
Secondary outcomes include other Patient Reported Outcome Measures (PROMS) to describe other aspects of health and wellbeing. These include EQ-5D-5L, Illness perception (Brief IPQ), Treatment satisfaction (TSQM), Duke Activity Status Index (DASI), the International Physical Activity Questionnaire (IPAQ-SF) short-form and a pain questionnaire.
There is preliminary evidence that small vessel disease can be a systemic problem affecting different organs. Whether small vessel disease in the heart might associate with small vessel disease in the brain or retina is unknown. In the CorMicA pilot study, studies of small vessels isolated from biopsies found evidence of endothelial dysfunction and increased responsiveness of the blood vessels to naturally-occurring, constriction-inducing peptides such as endothelin and thromboxane. For these reasons, we plan heart-brain-retina and peripheral vascular substudies.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention Group | Active comparator | Diagnostic Test: CMR results disclosedAll randomised participants will receive stratified medicine. The subjects will undergo stress perfusion CMR as an adjunct to invasive coronary angiography. The CMR results will be disclosed to the clinician to clarify endotypes and re-evaluate the clinical diagnosis. Linked guideline-directed medical therapy and lifestyle measures will be recommended based on the endotype. The patient and clinicians responsible for downstream care will not be informed of the randomised group but they will be informed of the endotype and linked treatment plan, in the same way as in the Standard Care control group. They will be blinded to the allocated study arm and CMR findings. |
| Standard Care Group | Sham comparator | Diagnostic Test: CMR performed but results not disclosedAll randomised participants in this arm will receive standard angiography-guided care. The endotype will be determined based on the angiogram and all of the available clinical information. The participants in this group will also undergo stress perfusion CMR but the results will not be disclosed. Management of the patient is as per standard of care, with therapy linked to the diagnosis (endotype). The patient and clinicians responsible for downstream care will not be informed of the randomised group but they will be informed of the endotype and linked treatment plan in the same way as in the Intervention Group. They will be blinded to the allocated study arm and CMR findings. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age ≥18 years
- Symptoms of angina or angina-equivalent informed by the Rose Angina questionnaire.
- Coronary angiography ≤3 months with a plan for medical management.
Key exclusion criteria (7 listed)
- Obstructive coronary artery disease i.e. a stenosis >70% in a single segment or 50 - 70% in 2 adjacent segments in an artery >2.5 mm, or FFR ≤0.80.
- Coronary revascularization by percutaneous coronary intervention or coronary artery bypass graft surgery following the index angiogram.
- Prior coronary artery bypass surgery
- A diagnosis that would explain the angina e.g. anaemia, aortic stenosis, hypertrophic cardiomyopathy,
- Contra-indication to contrast-enhanced CMR e.g. eGFR < 30mL/min/1.73m2.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CMR results disclosedThe results of the CMR are disclosed, and used to guide management | Diagnostic test | Intervention Group |
| CMR performed but results not disclosedThe results of the CMR are not disclosed, and management is angiography-guided | Diagnostic test | Standard Care Group |
Primary outcome
Reclassification of the initial diagnosis
Time frame: Day 1
The reclassification of the initial diagnosis based on invasive management following multi-parametric stress perfusion CMR. The diagnostic groups (endotypes) are: 1. Anginal symptoms with a myocardial perfusion defect indicative of obstructive CAD; 2. Anginal symptoms associated with a myocardial perfusion defect indicative of microvascular disease; 3. Vasospastic angina; 4. Incidental finding that is actionable e.g. aortic stenosis, cardiomyopathy, lung cancer; or 5. No clinically significant finding or normal.
Seattle Angina Questionnaire (SAQ) Summary Score
Time frame: 6 months
The 7-item version of the SAQ reflects the frequency of angina (SAQ Angina Frequency score) and the disease-specific effect of angina on patients' physical function (SAQ Physical Limitation score) and quality of life (Quality of Life score) over the previous 4 weeks; these scores are averaged to obtain the SAQ Summary score, which is an overall measure of patients' stable ischaemic heart disease-specific health status. SAQ scores range from 0 to 100, with higher scores indicating less frequent angina, improved function, and better quality of life.
27 secondary outcomes
Compliance with the protocol
Time frame: 0-36 months
Integrity of blinding in the Radiology Department and during follow-up
Time frame: 0-36 months
Diagnostic utility
Time frame: 0-36 months
Clinical Utility
Time frame: 0-36 months
Abnormal myocardial perfusion
Time frame: Day 1
Myocardial blood flow
Time frame: Day 1
Myocardial tissue characteristics
Time frame: Day 1
Cardiovascular risk
Time frame: Day 1
Within subject change in myocardial blood flow
Time frame: 0-12 months
Between-group, within subject change in myocardial blood flow
Time frame: 0-12 months
Health Status: EQ5D-5L Questionnaire
Time frame: 0-36 months
Health Status: Seattle Angina Questionnaire
Time frame: 0-36 months
Health Status: Illness Perception - Brief IPQ
Time frame: 0-36 months
Health Status: Treatment satisfaction - TSQM
Time frame: 0-36 months
Health Status: Duke Activity Status Index
Time frame: 0-36 months
Health Status: International Physical Activity Questionnaire- Short Form (IPAQ-SF)
Time frame: 0-36 months
Health Status: Montreal Cognitive Assessment (MOCA)
Time frame: 0-36 months
Correlation between myocardial blood flow and health status
Time frame: 0-36 months
Long term prognosis
Time frame: 0-20 years
Health Outcomes: Major Adverse Cardiovascular Events
Time frame: 0-20 years
Angina events
Time frame: 0-3 years
Brain small vessel disease
Time frame: 0-36 months
Correlation between small vessel disease in the brain and myocardial perfusion
Time frame: 0-36 months
Health economics: Inpatients visits
Time frame: 0-20 years
Health economics: Cardiac procedures
Time frame: 0-20 years
Health economics: Medication use
Time frame: 0-20 years
Work limitation
Time frame: 0-36 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2025.
- Background: PubMed 37467080Bradley CP, Berry C. Microvascular arterial disease of the brain and the heart: a shared pathogenesis. QJM. 2023 Oct 23;116(10):829-834. doi: 10.1093/qjmed/hcad158.
- Background: PubMed 37657593Bradley CP, Orchard V, McKinley G, Heggie R, Wu O, Good R, Watkins S, Lindsay M, Eteiba H, McGowan J, McGeoch R, Corcoran D, Kellman P, McConnachie A, Berry C. The coronary microvascular angina cardiovascular magnetic resonance imaging trial: Rationale and design. Am Heart J. 2023 Nov;265:213-224. doi: 10.1016/j.ahj.2023.08.067. Epub 2023 Aug 30.
- Background: PubMed 35534718Bradley C, Berry C. Definition and epidemiology of coronary microvascular disease. J Nucl Cardiol. 2022 Aug;29(4):1763-1775. doi: 10.1007/s12350-022-02974-x. Epub 2022 May 9.
- Background: PubMed 37795617Sidik NP, Stanley B, Sykes R, Morrow AJ, Bradley CP, McDermott M, Ford TJ, Roditi G, Hargreaves A, Stobo D, Adams J, Byrne J, Mahrous A, Young R, Carrick D, McGeoch R, Corcoran D, Lang NN, Heggie R, Wu O, McEntegart MB, McConnachie A, Berry C. Invasive Endotyping in Patients With Angina and No Obstructive Coronary Artery Disease: A Randomized Controlled Trial. Circulation. 2024 Jan 2;149(1):7-23. doi: 10.1161/CIRCULATIONAHA.123.064751. Epub 2023 Oct 5.
- BackgroundLudman P on behalf of the British Cardiovascular Intervention Society (BCIS). BCIS Audit Returns for Adult Interventional Procedures (Jan - Dec 2016). October 2017. https://www.bcis.org.uk/resources/audit-results/
- Background: PubMed 28246175Williams MC, Hunter A, Shah A, Assi V, Lewis S, Mangion K, Berry C, Boon NA, Clark E, Flather M, Forbes J, McLean S, Roditi G, van Beek EJ, Timmis AD, Newby DE; Scottish COmputed Tomography of the HEART (SCOT-HEART) Trial Investigators. Symptoms and quality of life in patients with suspected angina undergoing CT coronary angiography: a randomised controlled trial. Heart. 2017 Jul;103(13):995-1001. doi: 10.1136/heartjnl-2016-310129. Epub 2017 Feb 28.
- Background: PubMed 30266608Ford TJ, Stanley B, Good R, Rocchiccioli P, McEntegart M, Watkins S, Eteiba H, Shaukat A, Lindsay M, Robertson K, Hood S, McGeoch R, McDade R, Yii E, Sidik N, McCartney P, Corcoran D, Collison D, Rush C, McConnachie A, Touyz RM, Oldroyd KG, Berry C. Stratified Medical Therapy Using Invasive Coronary Function Testing in Angina: The CorMicA Trial. J Am Coll Cardiol. 2018 Dec 11;72(23 Pt A):2841-2855. doi: 10.1016/j.jacc.2018.09.006. Epub 2018 Sep 25.
- Background: PubMed 31709984Ford TJ, Stanley B, Sidik N, Good R, Rocchiccioli P, McEntegart M, Watkins S, Eteiba H, Shaukat A, Lindsay M, Robertson K, Hood S, McGeoch R, McDade R, Yii E, McCartney P, Corcoran D, Collison D, Rush C, Sattar N, McConnachie A, Touyz RM, Oldroyd KG, Berry C. 1-Year Outcomes of Angina Management Guided by Invasive Coronary Function Testing (CorMicA). JACC Cardiovasc Interv. 2020 Jan 13;13(1):33-45. doi: 10.1016/j.jcin.2019.11.001. Epub 2019 Nov 11.
- Background: PubMed 32624456Kunadian V, Chieffo A, Camici PG, Berry C, Escaned J, Maas AHEM, Prescott E, Karam N, Appelman Y, Fraccaro C, Buchanan GL, Manzo-Silberman S, Al-Lamee R, Regar E, Lansky A, Abbott JD, Badimon L, Duncker DJ, Mehran R, Capodanno D, Baumbach A. An EAPCI Expert Consensus Document on Ischaemia with Non-Obstructive Coronary Arteries in Collaboration with European Society of Cardiology Working Group on Coronary Pathophysiology & Microcirculation Endorsed by Coronary Vasomotor Disorders International Study Group. EuroIntervention. 2021 Jan 20;16(13):1049-1069. doi: 10.4244/EIJY20M07_01.
- Background: PubMed 32054665Ford TJ, Berry C. Angina: contemporary diagnosis and management. Heart. 2020 Mar;106(5):387-398. doi: 10.1136/heartjnl-2018-314661. Epub 2020 Feb 12. No abstract available.
- BackgroundCorcoran D, Ford T, Hsu LY, Orchard V, Oldroyd KG, Arai AE, Berry C, on behalf of the CorMicA Investigators. The diagnostic utility of multiparametric CMR in patients with angina and non-obstructive coronary artery disease. Eur Heart J. 2020;
- Background: PubMed 30772231Kotecha T, Martinez-Naharro A, Boldrini M, Knight D, Hawkins P, Kalra S, Patel D, Coghlan G, Moon J, Plein S, Lockie T, Rakhit R, Patel N, Xue H, Kellman P, Fontana M. Automated Pixel-Wise Quantitative Myocardial Perfusion Mapping by CMR to Detect Obstructive Coronary Artery Disease and Coronary Microvascular Dysfunction: Validation Against Invasive Coronary Physiology. JACC Cardiovasc Imaging. 2019 Oct;12(10):1958-1969. doi: 10.1016/j.jcmg.2018.12.022. Epub 2019 Feb 13.
- Individual participant dataSharing planned: Yes. Anonymised data may be shared based on a research agreement
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Colin Berry, MBChB, PhD principal investigator
Univerisity of Glasgow
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CMR results disclosed and CMR performed but results not disclosed in people with Microvascular Angina and Angina Pectoris, run by NHS National Waiting Times Centre Board at 3 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 3 inclusion and 7 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: under way, not looking for participants, as of the sponsor's last update on 30 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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. Some participants in this study may receive a placebo. 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?
This study is still under way. Results are not available in the source record yet.
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?
Reclassification of the initial diagnosis (time frame: Day 1). The study lists 2 primary outcomes in all. 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 NCT04805814, which also lists 19 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 30 Jan 2025.