CORonary MICrovascular Angina (CorMicA)

NCT03193294 | Completed

• 1 other identifier: 16CARD25
• Study Type: interventional
• Target: 151
• Locations: 1 country
• Sites: 2

Brief Summary

Angina is form of chest pain that is due to a lack of blood to the heart muscle. Angina is commonly triggered by stress and exertion, and is a common health problem worldwide. The diagnosis and treatment of angina is usually focused on detection of blockages in heart arteries, and relief of this problem with drugs, stents or bypass surgery. However, about one third of all invasive angiograms that are performed in patients with angina do not reveal any blockages. Many of such patients may have symptoms due to narrowings in the very small micro vessels (too small to be seen on an angiogram). The purpose of this research is to undertake a 'proof-of-concept' clinical trial to gather information as to whether routine tests of small vessel function in the heart might help identify patients with a stable coronary syndrome due to a disorder of coronary function (vasospastic or microvascular angina), and appropriately rule out this problem in patients with normal test results. The diagnostic strategy enables stratification of patient sub-groups to optimized therapy (personalised medicine). Evidence of patient benefits in this study would support the plan for a larger study that would be designed to impact on healthcare costs and patient reported outcome measures (PROMS).

Conditions

Angina, Stable; Coronary Vasospasm; Coronary Circulation; Coronary Syndrome; Microvascular Angina; Coronary Disease

Outcome Measures

Primary Outcomes (1)

• Health status (Seattle Angina Score)

  Health status and symptoms will be assessed at baseline and again at 6 months using the Seattle Angina Questionnaire. The primary outcome is the within-subject change in SAQ score at 6 months from baseline.

  6 months

Secondary Outcomes (16)

• Feasibility of the stratified medicine approach defined by protocol compliance as measured by deviations from the protocol.

  Through study completion, 3 years

• Procedure-related serious adverse events

  Day 1 (index coronary angiogram procedure)

• Prevalence of endotypes

  Day 1

• Diagnostic utility of the diagnostic intervention

  Day 1

• Clinical utility of the stratified approach

  Day 1

Study Arms (2)

Intervention group (coronary function test results disclosed)

ACTIVE COMPARATOR

In the intervention group, coronary function tests are measured and disclosed to the attending clinician permitting re-evaluation of the initial diagnosis and treatment as compared with initial angiography-guided decisions. The intervention involves measurement of CFR, IMR and RRR in a target, major coronary artery followed by coronary reactivity testing using incremental doses of acetylcholine (10-4M, 10-5M, 10-6M) to assess endothelial function, bolus infusion of ACh (10-4M) for vasospasm provocation testing, followed by administration of a bolus dose (300 micrograms) of glyceryl trinitrate. Endotypes are identified based on established criteria for abnormalities in coronary vasodilator function, vasospasm and microvascular resistance. The endotypes (diagnostic strata) are: obstructive CAD, coronary artery spasm, microvascular angina, endothelial dysfunction (no angina), normal (non-cardiac). A diagnosis may be ruled-in or ruled-out based on the test results.

Diagnostic Test: Stratified medicine involving a diagnostic intervention

Usual care group (coronary function results not disclosed)

SHAM COMPARATOR

Coronary function tests are measured but not disclosed to the attending clinician or the participant. The same coronary function tests are undertaken as in the intervention group. Masking is achieved by obscuring the catheter laboratory monitors from the attending clinician and participant. The effectiveness of masking is prospectively monitored.

Diagnostic Test: Stratified medicine involving a diagnostic intervention

Interventions

Stratified medicine involving a diagnostic intervention DIAGNOSTIC_TEST

Adjunctive tests of coronary artery function at the time of invasive coronary angiography. Diagnostic groups: stable coronary syndromes in patients with no-obstructive coronary artery disease including the following sub-groups (coronary artery vasospasm, microvascular spasm, impaired vasorelaxation due to (1) endothelial dysfunction and/or (2) non-endothelial dysfunction, or unaffected (normal test results). Medical management is linked to contemporary clinical guidelines for the management of patients with stable coronary artery disease (European Society of Cardiology (2013)).

Intervention group (coronary function test results disclosed); Usual care group (coronary function results not disclosed)

Eligibility Criteria

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

You may qualify if:

• A clinically-indicated plan for invasive coronary angiography. Symptoms of angina or angina-equivalent (according to the Rose- and Seattle Angina questionnaires).

You may not qualify if:

• A non-coronary indication for invasive angiography e.g. valve disease During the angiogram: obstructive disease evident in a main coronary artery (diameter \>2.5 mm), i.e. a coronary stenosis\>50% or a fractional flow reserve (FFR) ≤0.80 Lack of informed consent.

Sponsors & Collaborators

• NHS National Waiting Times Centre Board: lead
• British Heart Foundation: collaborator

Study Sites (2)

Golden Jubilee National Hospital

Clydebank, Dunbartonshire, G814DY, United Kingdom

Location

Hairmyres Hospital

East Kilbride, Lanarkshire, G75 8RG, United Kingdom

Location

Related Publications (23)

• Ford TJ, Ong P, Sechtem U, Beltrame J, Camici PG, Crea F, Kaski JC, Bairey Merz CN, Pepine CJ, Shimokawa H, Berry C; COVADIS Study Group. Assessment of Vascular Dysfunction in Patients Without Obstructive Coronary Artery Disease: Why, How, and When. JACC Cardiovasc Interv. 2020 Aug 24;13(16):1847-1864. doi: 10.1016/j.jcin.2020.05.052.

  PMID: 32819476 BACKGROUND

• Ford TJ, Corcoran D, Sidik N, Oldroyd KG, Rocchiccioli P, McEntegart M, Berry C. MINOCA: Requirement for Definitive Diagnostic Work-Up. Heart Lung Circ. 2019 Feb;28(2):e4-e6. doi: 10.1016/j.hlc.2018.04.001. No abstract available.

  PMID: 30654950 BACKGROUND

• Collison D, Copt S, Mizukami T, Collet C, McLaren R, Didagelos M, Aetesam-Ur-Rahman M, McCartney P, Ford TJ, Lindsay M, Shaukat A, Rocchiccioli P, Brogan R, Watkins S, McEntegart M, Good R, Robertson K, O'Boyle P, Davie A, Khan A, Hood S, Eteiba H, Berry C, Oldroyd KG. Angina After Percutaneous Coronary Intervention: Patient and Procedural Predictors. Circ Cardiovasc Interv. 2023 Apr;16(4):e012511. doi: 10.1161/CIRCINTERVENTIONS.122.012511. Epub 2023 Mar 28.

  PMID: 36974680 BACKGROUND

• Rush CJ, Berry C, Oldroyd KG, Rocchiccioli JP, Lindsay MM, Touyz RM, Murphy CL, Ford TJ, Sidik N, McEntegart MB, Lang NN, Jhund PS, Campbell RT, McMurray JJV, Petrie MC. Prevalence of Coronary Artery Disease and Coronary Microvascular Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction. JAMA Cardiol. 2021 Oct 1;6(10):1130-1143. doi: 10.1001/jamacardio.2021.1825.

  PMID: 34160566 BACKGROUND

• Kunadian V, Chieffo A, Camici PG, Berry C, Escaned J, Maas AHEM, Prescott E, Karam N, Appelman Y, Fraccaro C, Louise Buchanan G, 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. Eur Heart J. 2020 Oct 1;41(37):3504-3520. doi: 10.1093/eurheartj/ehaa503.

  PMID: 32626906 BACKGROUND

• Vrints C, Andreotti F, Koskinas KC, Rossello X, Adamo M, Ainslie J, Banning AP, Budaj A, Buechel RR, Chiariello GA, Chieffo A, Christodorescu RM, Deaton C, Doenst T, Jones HW, Kunadian V, Mehilli J, Milojevic M, Piek JJ, Pugliese F, Rubboli A, Semb AG, Senior R, Ten Berg JM, Van Belle E, Van Craenenbroeck EM, Vidal-Perez R, Winther S; ESC Scientific Document Group. 2024 ESC Guidelines for the management of chronic coronary syndromes. Eur Heart J. 2024 Sep 29;45(36):3415-3537. doi: 10.1093/eurheartj/ehae177. No abstract available.

  PMID: 39210710 BACKGROUND

• Cannon RO 3rd, Leon MB, Watson RM, Rosing DR, Epstein SE. Chest pain and "normal" coronary arteries--role of small coronary arteries. Am J Cardiol. 1985 Jan 25;55(3):50B-60B. doi: 10.1016/0002-9149(85)90613-7.

  PMID: 3969858 BACKGROUND

• Cannon RO 3rd, Bonow RO, Bacharach SL, Green MV, Rosing DR, Leon MB, Watson RM, Epstein SE. Left ventricular dysfunction in patients with angina pectoris, normal epicardial coronary arteries, and abnormal vasodilator reserve. Circulation. 1985 Feb;71(2):218-26. doi: 10.1161/01.cir.71.2.218.

  PMID: 3965167 BACKGROUND

• Sax FL, Cannon RO 3rd, Hanson C, Epstein SE. Impaired forearm vasodilator reserve in patients with microvascular angina. Evidence of a generalized disorder of vascular function? N Engl J Med. 1987 Nov 26;317(22):1366-70. doi: 10.1056/NEJM198711263172202.

  PMID: 3683470 BACKGROUND

• Kaski JC, Elliott PM, Salomone O, Dickinson K, Gordon D, Hann C, Holt DW. Concentration of circulating plasma endothelin in patients with angina and normal coronary angiograms. Br Heart J. 1995 Dec;74(6):620-4. doi: 10.1136/hrt.74.6.620.

  PMID: 8541166 BACKGROUND

• Elliott PM, Krzyzowska-Dickinson K, Calvino R, Hann C, Kaski JC. Effect of oral aminophylline in patients with angina and normal coronary arteriograms (cardiac syndrome X). Heart. 1997 Jun;77(6):523-6. doi: 10.1136/hrt.77.6.523.

  PMID: 9227295 BACKGROUND

• Beltrame JF, Crea F, Kaski JC, Ogawa H, Ong P, Sechtem U, Shimokawa H, Bairey Merz CN; Coronary Vasomotion Disorders International Study Group (COVADIS). The Who, What, Why, When, How and Where of Vasospastic Angina. Circ J. 2016;80(2):289-98. doi: 10.1253/circj.CJ-15-1202. Epub 2015 Dec 18.

  PMID: 26686994 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, Corcoran D, Berry C. Coronary artery disease: physiology and prognosis. Eur Heart J. 2017 Jul 1;38(25):1990-1992. doi: 10.1093/eurheartj/ehx226. No abstract available.

  PMID: 28549103 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

• Sidik NP, McEntegart M, Roditi G, Ford TJ, McDermott M, Morrow A, Byrne J, Adams J, Hargreaves A, Oldroyd KG, Stobo D, Wu O, Messow CM, McConnachie A, Berry C. Rationale and design of the British Heart Foundation (BHF) Coronary Microvascular Function and CT Coronary Angiogram (CorCTCA) study. Am Heart J. 2020 Mar;221:48-59. doi: 10.1016/j.ahj.2019.11.015. Epub 2019 Dec 2.

  PMID: 31911341 BACKGROUND

• Ford TJ, Yii E, Sidik N, Good R, Rocchiccioli P, McEntegart M, Watkins S, Eteiba H, Shaukat A, Lindsay M, Robertson K, Hood S, McGeoch R, McDade R, McCartney P, Corcoran D, Collison D, Rush C, Stanley B, McConnachie A, Sattar N, Touyz RM, Oldroyd KG, Berry C. Ischemia and No Obstructive Coronary Artery Disease: Prevalence and Correlates of Coronary Vasomotion Disorders. Circ Cardiovasc Interv. 2019 Dec;12(12):e008126. doi: 10.1161/CIRCINTERVENTIONS.119.008126. Epub 2019 Dec 13.

  PMID: 31833416 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

• Ford TJ, Berry C. How to Diagnose and Manage Angina Without Obstructive Coronary Artery Disease: Lessons from the British Heart Foundation CorMicA Trial. Interv Cardiol. 2019 May 21;14(2):76-82. doi: 10.15420/icr.2019.04.R1. eCollection 2019 May.

  PMID: 31178933 BACKGROUND

• Corcoran D, Ford TJ, Hsu LY, Chiribiri A, Orchard V, Mangion K, McEntegart M, Rocchiccioli P, Watkins S, Good R, Brooksbank K, Padmanabhan S, Sattar N, McConnachie A, Oldroyd KG, Touyz RM, Arai A, Berry C. Rationale and design of the Coronary Microvascular Angina Cardiac Magnetic Resonance Imaging (CorCMR) diagnostic study: the CorMicA CMR sub-study. Open Heart. 2018 Dec 30;5(2):e000924. doi: 10.1136/openhrt-2018-000924. eCollection 2018.

  PMID: 30687508 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

• Ford TJ, Corcoran D, Padmanabhan S, Aman A, Rocchiccioli P, Good R, McEntegart M, Maguire JJ, Watkins S, Eteiba H, Shaukat A, Lindsay M, Robertson K, Hood S, McGeoch R, McDade R, Yii E, Sattar N, Hsu LY, Arai AE, Oldroyd KG, Touyz RM, Davenport AP, Berry C. Genetic dysregulation of endothelin-1 is implicated in coronary microvascular dysfunction. Eur Heart J. 2020 Sep 7;41(34):3239-3252. doi: 10.1093/eurheartj/ehz915.

  PMID: 31972008 DERIVED

• 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 DERIVED

Related Links

• Cardiology and Imaging Group, University of Glasgow
• British Heart Foundation

MeSH Terms

Conditions

Angina, Stable; Coronary Vasospasm; Angina, Unstable; Microvascular Angina; Coronary Disease

Condition Hierarchy (Ancestors)

Angina Pectoris; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Katriona Brooksbank, PhD

  University of Glasgow

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Participants are randomised to a 'Disclosed group' (Intervention group) or a 'Not disclosed group' (Standard Care). In the standard care group, coronary function parameters are measured but the results are not disclosed to the attending clinician or the participant.
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Cardiology and Imaging

Model Details: Randomized, double-blind, parallel group, prospective

Study Record Dates

• First Submitted: June 13, 2017
• First Posted: June 20, 2017
• Study Start: November 7, 2016
• Primary Completion: July 31, 2019
• Study Completion: November 6, 2019
• Last Updated: October 29, 2024

Record last verified: 2024-10

Locations

GB (2)