Coronary Microvascular Angina Cardiac Magnetic Resonance Imaging (CorCMR) Trial

NCT04805814 | Active Not Recruiting DMC

• 1 other identifier: 281128
• Study Type: interventional
• Target: 280
• Locations: 1 country
• Sites: 3

Brief 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. 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.

Conditions

Microvascular Angina; Angina Pectoris; Angina, Stable; Non-Obstructive Coronary Atherosclerosis; Small Vessel Cerebrovascular Disease; Coronary Artery Disease

Outcome Measures

Primary Outcomes (2)

• 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: 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.

  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.

  6 months

Secondary Outcomes (27)

• Compliance with the protocol

  0-36 months

• Integrity of blinding in the Radiology Department and during follow-up

  0-36 months

• Diagnostic utility

  0-36 months

• Clinical Utility

  0-36 months

• Abnormal myocardial perfusion

  Day 1

Other Outcomes (2)

• Small vessel substudy

  0-12 months

• Retinal imaging substudy

  0-12 months

Study Arms (2)

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.

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.

Diagnostic Test: CMR performed but results not disclosed

Interventions

CMR results disclosed DIAGNOSTIC_TEST

The results of the CMR are disclosed, and used to guide management

Intervention Group

CMR performed but results not disclosed DIAGNOSTIC_TEST

The results of the CMR are not disclosed, and management is angiography-guided

Standard Care Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• NHS National Waiting Times Centre Board: lead
• University of Glasgow: collaborator
• British Heart Foundation: collaborator
• Chief Scientist Office of the Scottish Government: collaborator

Study Sites (3)

University Hospital Hairmyres

East Kilbride, Glasgow, G75 8RG, United Kingdom

Location

University Hospital Ayr

Ayr, Scotland, KA6 6D, United Kingdom

Location

Golden Jubilee National Hospital

Glasgow, Scotland, G81 4DY, United Kingdom

Location

Related Publications (18)

• 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.

  PMID: 37467080 BACKGROUND

• Bradley 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.

  PMID: 37657593 BACKGROUND

• Bradley 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.

  PMID: 35534718 BACKGROUND

• Sidik 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.

  PMID: 37795617 BACKGROUND

• Ludman 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

• 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.

  PMID: 28246175 BACKGROUND

• Ford 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.

  PMID: 30266608 BACKGROUND

• Ford 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.

  PMID: 31709984 BACKGROUND

• Kunadian 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.

  PMID: 32624456 BACKGROUND

• Ford 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.

  PMID: 32054665 BACKGROUND

• Corcoran 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

• 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.

  PMID: 30772231 BACKGROUND

• Hsu 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.

  PMID: 29454767 BACKGROUND

• Knott 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.

  PMID: 32078380 BACKGROUND

• Berry 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.

  PMID: 30712442 BACKGROUND

• Ford TJ, Rocchiccioli P, Good R, McEntegart M, Eteiba H, Watkins S, Shaukat A, Lindsay M, Robertson K, Hood S, Yii E, Sidik N, Harvey A, Montezano AC, Beattie E, Haddow L, Oldroyd KG, Touyz RM, Berry C. Systemic microvascular dysfunction in microvascular and vasospastic angina. Eur Heart J. 2018 Dec 7;39(46):4086-4097. doi: 10.1093/eurheartj/ehy529.

  PMID: 30165438 BACKGROUND

• Bradley CP, McKinley G, Orchard V, Tiller C, Stanley B, Ang D, Morrow AJ, Sykes R, Gildea P, Petty M, Brogan R, Carrick D, Collison D, Eteiba H, Ghattas A, Good R, Joshi F, Lindsay M, McCartney P, McGowan J, McGeoch R, Robertson K, Rocchiccioli P, Shaukat A, Watkins S, Kellman P, McConnachie A, Berry C. Endotyping-informed therapy for patients with chest pain and no obstructive coronary artery disease: a randomized trial. Nat Med. 2026 Jan;32(1):332-341. doi: 10.1038/s41591-025-04044-4. Epub 2025 Nov 10.

  PMID: 41214345 DERIVED

• Bradley CP, Orchard V, Sykes RA, McKinley G, McConnachie A, Donnelly P, Watt J, Kellman P, Quinn T, Fullerton N, Berry C. Heart-brain microvascular MRI study: protocol for a multicentre, observational, cohort study in the UK assessing associations between small vessel disease of the heart and brain. BMJ Open. 2024 Dec 20;14(12):e088372. doi: 10.1136/bmjopen-2024-088372.

  PMID: 39806582 DERIVED

MeSH Terms

Conditions

Microvascular Angina; Angina Pectoris; Angina, Stable; Cerebral Small Vessel Diseases; Coronary Artery Disease

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Coronary Disease; Arteriosclerosis; Arterial Occlusive Diseases

Study Officials

• Colin Berry, MBChB, PhD

  Univerisity of Glasgow

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Investigator

Study Record Dates

• First Submitted: March 9, 2021
• First Posted: March 18, 2021
• Study Start: February 9, 2021
• Primary Completion: October 1, 2024
• Study Completion (Estimated): October 1, 2034
• Last Updated: January 30, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: After the study has completed
• Access Criteria: Bone fide collaboration request

Locations

GB (3)