Microvascular AnginaiCorMicANCT04674449
iCorMicA - Stratified Medicine in Angina
A study testing Disclosure of IDP results and IDP performed but results not disclosed in people with Microvascular Angina and Angina, Stable, run by NHS Greater Glasgow and Clyde at 39 sites in 4 countries.
Trial summary
The iCorMicA study is a multicentre, prospective, randomised, double-blind, sham-controlled, parallel-group, end-point trial and registry. The investigators seek to determine whether stratified medical therapy guided by an adjunctive interventional diagnostic procedure (IDP) during the invasive management of patients… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Microvascular Angina, Angina, Stable, Ischemia With No Obstructive Coronary Arteries (INOCA)
- What is being tested?
- Disclosure of IDP results and IDP performed but results not disclosed
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,500 participants
- Where
- 39 sitesin 4 countries
- Study dates
- 30 Dec 2020to 31 Dec 2030
- 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.
- A clinical plan for invasive coronary angiography.
- Symptoms of angina (typical or atypical) according to the Rose- and/or Seattle Angina questionnaires.
- Able to comply with study procedures.
- Able to provide informed consent.
Who cannot join
- A non-coronary primary indication for invasive angiography (e.g. valve disease, heart failure).
- History of coronary artery bypass surgery.
- Presence of obstructive disease evident in a main coronary artery (diameter >2.5 mm), i.e. a coronary stenosis >50% and/or a fractional flow reserve (FFR) ≤0.80*.
- Logistical reason*. *These patients will enter a follow-up registry.
Trial locations and contacts
39 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
Daniel Ang, MBChB contact
39 sites in 4 countries
United Kingdom35 sites, 29 recruiting
- Completed
Aberdeen Royal Hospital
Aberdeen
- Recruiting
William Harvey Hospital
Ashford
Rajiv Rampat, rajiv.rampat@nhs.net
- Completed
Basildon University Hospital - Essex Cardiothoracic Centre
Basildon
- Recruiting
Bedford Hospital NHS Trust
Bedford
Sudipta Chattopadhyay, sudipta.chattopadhyay@bedsft.nhs.uk
- Recruiting
Royal Victoria Hospital
Belfast
Colum Owens, colum.owens@belfasttrust.hscni.net
- Recruiting
Birmingham Heartlands Hospital
Birmingham
Shamin Rahman, shamim.rahman@nhs.net
- Recruiting
Royal Blackburn Teaching Hospital
Blackburn
Kanarath Balachandran, kanarath.balachandran@elht.nhs.uk
- Recruiting
Victoria Hospital
Blackpool
Gavin Galaskpo, dr.galasko@nhs.net
- Recruiting
Glan Clwyd Hospital
Bodelwyddan
Eduardas Subkovas, eduardas.subkovas@wales.nhs.uk
- Completed
Royal Bournemouth Hospital
Bournemouth
- Active, not recruiting
Royal Papworth Hospital NHS Foundation Trust
Cambridge
- Recruiting
University Hospital of Wales
Cardiff
Rito Mitra, Rito Mitra (CTM UHB - Cardiology) <Rito.Mitra@wales.nhs.uk>
- Recruiting
St Peter's Hospital NHS Foundation Trust
Chertsey
Sumeet Sharma, sumeetsharma@nhs.net
- Recruiting
Golden Jubilee National Hospital
Clydebank, Scotland, G814DY
Damien Collison, MBChB, 441419515000, Damien.Collison@gjnh.scot.nhs.uk
Daniel Ang, MBChB, 441419515000, Daniel.Ang@glasgow.ac.uk
- Recruiting
University Hospitals Coventry & Warwickshire NHS Trust
Coventry
Ashwin Radhakrishnan, ashwin.radhakrishnan@uhcw.nhs.uk
- Recruiting
University Hospital Hairmyres
East Kilbride
David Carrick, david.carrick@lanarkshire.scot.nhs.uk
- Not yet recruiting
NHS Greater Glasgow and Clyde
Glasgow
Diann Taggart, +44 141 314 4407, diann.taggart@ggc.scot.nhs.uk
- Recruiting
Raigmore Hospital
Inverness
Iskander Zaid, zaid.iskandar2@nhs.scot
- Recruiting
Leeds Teaching Hospital NHS Trust
Leeds
John Greenwood, j.greenwood@leeds.ac.uk
- Recruiting
Liverpool Heart and Chest Hospital
Liverpool
Joel Giblet, joel.giblett@lhch.nhs.uk
- Recruiting
Royal Free Hospital
London, NW3
Tim Lockie, tim.lockie@nhs.net
- Active, not recruiting
Barts Health NHS Trust - St. Bartholomew's Hospital
London
- Recruiting
King's College Hospital
London
Kevin O'Gallagher, kevin.o'gallagher@kcl.ac.uk
- Recruiting
Northwick Park Hospital
London
Ahmed El-Ghamaz, ahmedelghamaz@nhs.net
- Recruiting
The Newcastle upon Tyne Hospitals NHS Foundation Trust
Newcastle upon Tyne
Ian Purcell, ian.purcell@nhs.net
- Recruiting
Royal Gwent Hospital
Newport
David Turpie, david.turpie@wales.nhs.uk
- Recruiting
Nottingham University Hospitals NHS TRUST
Nottingham
Sachin Jadhav, sachin.jadhav@nhs.net
- Recruiting
Queen Alexandra Hospital
Portsmouth
Brijesh Anantharam, brijesh.anantharam@porthosp.nhs.uk
- Recruiting
Northern General Hospital
Sheffield
Paul Morris, paul.morris@sheffield.ac.uk
- Recruiting
University Hospital Southampton
Southampton
Nick Curzen, nick.curzen@uhs.nhs.uk
- Recruiting
South Tyneside and Sunderland NHS Foundation Trust
Sunderland
Yogesh Raja, yogesh.raja@nhs.net
- Recruiting
Morriston Hospital
Swansea
Anirban Choudhury, anirban.choudhury@wales.nhs.uk
- Recruiting
Pinderfields General Hospital
Wakefield
Ahmed Sabra, a.sabra@nhs.net
- Completed
Watford general Hospital
Watford
- Recruiting
New Cross Hospital
Wolverhampton
James Cotton, jamescotton@nhs.net
Ireland2 sites
- Completed
Mater Private Hsopital
Cork
- Completed
Mater Private Hospital
Dublin
Netherlands1 site, 1 recruiting
- Recruiting
Radboud University Medical Centre
Nijmegen
Peter Damman Dr, peter.damman@radboudumc.nl
Behruz Yosofi, behruz.yosofi@radboudumc.nl
Poland1 site, 1 recruiting
- Recruiting
5th Military Hospital
Krakow
Bartlomeij Guzik, behruz.yosofi@radboudumc.nl
About this study
Official title: International Study of Coronary Microvascular Angina (iCorMicA): a Randomised, Controlled, Multicentre Trial and Registry
The iCorMicA study is a multicentre, prospective, randomised, double-blind, sham-controlled, parallel-group, end-point trial and registry. The investigators seek to determine whether stratified medical therapy guided by an adjunctive interventional diagnostic procedure (IDP) during the invasive management of patients with known or suspected angina but no obstructive coronary artery disease improves symptoms, wellbeing, cardiovascular risk and clinical outcomes.
Read the detailed description
Ischaemic heart disease (IHD) includes coronary artery disease (or 'coronary heart disease 'CHD') and ischaemic with no obstructive coronary arteries (INOCA). Coronary angiography is standard care for the evaluation of symptomatic patients and known or suspected coronary artery disease. A considerable proportion e.g. >1 in 3, of patients undergoing invasive coronary angiography for known or suspected angina do not have obstructive epicardial coronary artery disease.
The CorMicA pilot study involved prospective enrolment of patients referred for clinically indicated coronary angiography during a 12-month period (2016-2017) in the West of Scotland). 391 patients were enrolled, 185 (47%) had no obstructive coronary disease and 151 were randomised in a clinical trial of stratified medicine based on invasive tests of coronary vascular function. A high proportion (~4 in 5) of these patients had a diagnosis of INOCA due to a disorder of coronary vasomotion including microvascular- and/or vasospastic angina. The trial provided preliminary evidence that stratified medicine, as an adjunct to standard angiography-guided management, has potential to improve symptoms and quality of life. The mechanisms involved changes in diagnosis, treatment and lifestyle measures.
The CorMicA investigators were the first group to introduce stratified medicine for the management of ischaemic heart disease. Limitations of the CorMicA study included the setting (mainly single centre), partial blinding, short-term follow-up (primary outcome at 6 months) and the sample size. Acetylcholine reactivity testing was used to assess the susceptibility to coronary spasm (microvascular and/or macrovascular). Although acetylcholine is a naturally occurring substance, current formulations are not licensed for parenteral administration. Further, clinicians should have training and experience before implementing acetylcholine coronary reactivity testing. These considerations present a barrier to adoption in daily practice, which becomes all the more relevant given INOCA is generally under-recognised. A diagnostic coronary guidewire is already widely used in standard care and, unlike reactivity testing using acetylcholine, a guidewire has transferable potential to support stratified medicine during routine practice. This is especially the case for ad-hoc follow-on testing when obstructive coronary artery disease is excluded.
The vasoactive responses to acetylcholine reflect endothelial and vascular smooth muscle cell effects, which may overlap with the vasoactive responses to adenosine (non-endothelial dependent). Calcium channel blocker therapy is indicated for the functional endotypes associated with impaired vasodilatation and/or vasoconstriction. This raises the possibility that acetylcholine testing may not be routinely required as an adjunctive test to coronary angiography and instead could be reserved for selected cases, or in specialist centres. Instead, the diagnostic guidewire approach may be sufficient as a routine, first line test for the evaluation of INOCA during daily practice.
Anatomical imaging using coronary angiography is the standard of care and clinicians may determine any diagnosis based on all of the available information and their clinical judgement. This approach avoids the need for additional tests. With this approach, the patient's symptoms in response to empirical therapy can be assessed during follow-up and the treatment can be revised as clinically appropriate. In daily practice, adoption of adjunctive tests of coronary function is very low and, in the absence of large, multicentre trials, coronary angiography with or without adjunctive tests of coronary vascular function may be considered reasonable, reflecting equipoise.
iCorMicA is a multicentre, prospective, randomised, double-blind, sham-controlled, parallel-group, end-point (patient reported outcome measures (PROMS), health outcomes, health economics) trial and registry. The investigators aim to determine whether stratified medical therapy, guided by a guidewire-based interventional diagnostic procedure (IDP) at the time of invasive coronary angiography (i.e. functional angiography), improves outcomes in patients with known or suspected angina but no obstructive coronary artery disease. Symptoms of angina or angina-equivalent are determined according to the Rose and/or Seattle Angina questionnaires. The IDP utilises principles of thermodilution to measure coronary vascular function (IMR, CFR, RRR), which aid clinicians in establishing a diagnosis of microvascular angina, vasospastic angina, mixed (both), or none, as per Coronary Vasomotion Disorders International Study Group (COVADIS) criteria. The feasibility, safety, efficacy and effect on healthcare resource utilisation of stratified medicine will be tested in multiple hospitals in different countries in Europe.
Participants with no obstructive epicardial coronary artery disease (coronary stenosis <50% and/or FFR >0.80) are eligible for randomisation (1:1) to either the intervention (IDP-guided, results disclosed) or blinded control (IDP undertaken but results not disclosed, standard of care) group. Medical therapy will be informed according to the clinical diagnosis (endotype). Patients in the intervention group with abnormal coronary vascular function may undergo repeated evaluations to assess the response to intracoronary therapy e.g. calcium channel blocker, enabling a personalised treatment plan. Patients who are ineligible for randomisation (e.g. obstructive coronary artery disease) may be entered into a prospective clinical registry, with individuals from each site invited to undergo similar follow-up assessments as the randomised participants.
Trial participants will be blinded to treatment group. The clinicians responsible for on-going care will also be blinded. Following invasive management, patients and clinicians will be advised of the diagnosis (endotype) but not the randomised group. The endotype will be informed by the IDP in the intervention group but not in the control group (sham procedure). 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 1500 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 measure is the Summary Score of the Seattle Angina Questionnaire at 12 months. 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.
Additional objectives include the wider evaluation of the safety and diagnostic utility of the IDP in a multicentre, multinational setting, and the effects of stratified medicine on the rates of major adverse cardiovascular events by randomised group. The registry will represent a parallel control group. Scientific analyses of circulating biomarkers will be performed to better understand the pathophysiology of INOCA.
- Conditions
- Microvascular Angina, Angina, Stable, Ischemia With No Obstructive Coronary Arteries (INOCA), Coronary Microvascular Dysfunction (CMD), Ischaemic Heart Disease, Non-Obstructive Coronary Atherosclerosis
- Being tested
- Disclosure of IDP results, IDP performed but results not disclosed
- Keywords
- angina, microvascular angina, ischaemia with no obstructive coronary artery disease (INOCA), stratified medicine, clinical trial, outcomes research, prognosis, health economics
- Medical subject headings
- Microvascular Angina, Angina, Stable, Coronary Artery Disease, Angina Pectoris, Variant, Ischemia, Angina Pectoris
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Disclosure of IDP resultsDiagnostic test
Also called Stratified medicine
The results of the adjunctive IDP performed at time of invasive coronary angiography are made available to the catheter laboratory clinician, to aid in the diagnostic process.
IDP performed but results not disclosedOther
Also called Standard, angiography-guided management
The results of the IDP performed at the time of invasive coronary angiography are concealed from the catheter laboratory clinician who will be blinded. The patient is managed according to standard of care.
| Study group | Role | What they receive |
|---|---|---|
| Intervention Group - Stratified Medicine | Active comparator | All randomised participants will receive stratified medicine. The subjects will undergo functional coronary angiography involving guidewire-based coronary function tests (interventional diagnostic procedure, IDP) as an adjunct to invasive coronary angiography. The IDP results will be disclosed to the catheter laboratory 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 IDP findings. Receives: Diagnostic Test: Disclosure of IDP results |
| 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 receive the IDP at time of the angiogram. The results of the IDP will be concealed from the catheter laboratory clinician who will be blinded. The cardiac physiologist / clinical scientist will remain unblinded for the purpose of data recording and quality assurance. The sham procedure is intended to be the same as in the Intervention Group. 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 IDP findings. Receives: Other: IDP performed but results not disclosed |
What is being measured
The primary outcome is the main question the study is designed to answer.
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: 12 months
Secondary outcomes (8)
Feasibility of stratified medicine
Rates of enrolment, drop-out, completion of diagnostic protocol, integrity of blinding in the catheter laboratory and blinding at 1 year, loss to follow-up.
Measured: 0-60 months
Safety of the interventional diagnostic procedure (IDP)
As reflected by SAEs related to the procedure, and those arising during longer term follow-up.
Measured: 0-60 months
Diagnostic utility of the interventional diagnostic procedure (IDP)
To assess impact of disclosure of the coronary function test results on the diagnosis and certainty of the diagnosis. A missed diagnosis of microvascular angina is defined as a physician diagnosis of non-cardiac chest pain in the presence of objective abnormalities of coronary artery function.
Measured: 0-60 months
Clinical utility
To assess the impact of disclosure of coronary function test results on clinical management (including treatment medication, investigations and healthcare resource utilisation).
Measured: 0-60 months
Health status
To assess quality of life, symptoms and health status using validated, patient-administered questionnaires. The EQ5D, SAQ, angina diary, EQ-5D-5L, Brief IPQ, TSQM, DASI, IPAQ-SF, FSQ and MOCA questionnaires will be completed.
Measured: 0-60 months
Cardiovascular risk
To assess attainment of guideline targets for measured cardiovascular risk factors, and adherence.
Measured: 0-60 months
Health outcomes
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 months - 10 years
Health economics
Health resource utilisation will also be assessed by identifying inpatient visits, procedures and medication use.
Measured: 0 months - 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2020
- Study start30 Dec 2020
- Primary completion30 Jun 2026 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)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
- 1,500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NHS Greater Glasgow and Clyde
- Sponsor type
- University, hospital or other
- Collaborators
- University of Glasgow, Abbott Medical Devices
- Responsible party
- Sponsor
- Investigators
- Colin Berry, MBChB, PhD, Study chair, University of Glasgow
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04674449
- Sponsor's protocol ID
- GN19CA435
- Acronym
- iCorMicA
- Status last verified
- Apr 2026
- First submitted
- 24 Jun 2020
- Last updated
- 9 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
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.
PubMed 32626906Bairey Merz CN, Pepine CJ, Walsh MN, Fleg JL. Ischemia and No Obstructive Coronary Artery Disease (INOCA): Developing Evidence-Based Therapies and Research Agenda for the Next Decade. Circulation. 2017 Mar 14;135(11):1075-1092. doi: 10.1161/CIRCULATIONAHA.116.024534.
PubMed 28289007Ford 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 30266608Jespersen L, Hvelplund A, Abildstrom SZ, Pedersen F, Galatius S, Madsen JK, Jorgensen E, Kelbaek H, Prescott E. Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. Eur Heart J. 2012 Mar;33(6):734-44. doi: 10.1093/eurheartj/ehr331. Epub 2011 Sep 11.
PubMed 21911339Sara JD, Widmer RJ, Matsuzawa Y, Lennon RJ, Lerman LO, Lerman A. Prevalence of Coronary Microvascular Dysfunction Among Patients With Chest Pain and Nonobstructive Coronary Artery Disease. JACC Cardiovasc Interv. 2015 Sep;8(11):1445-1453. doi: 10.1016/j.jcin.2015.06.017.
PubMed 26404197Ford 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.
PubMed 31833416Ford 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 31709984Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C, Prescott E, Storey RF, Deaton C, Cuisset T, Agewall S, Dickstein K, Edvardsen T, Escaned J, Gersh BJ, Svitil P, Gilard M, Hasdai D, Hatala R, Mahfoud F, Masip J, Muneretto C, Valgimigli M, Achenbach S, Bax JJ; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020 Jan 14;41(3):407-477. doi: 10.1093/eurheartj/ehz425. No abstract available.
PubMed 31504439Ong P, Camici PG, Beltrame JF, Crea F, Shimokawa H, Sechtem U, Kaski JC, Bairey Merz CN; Coronary Vasomotion Disorders International Study Group (COVADIS). International standardization of diagnostic criteria for microvascular angina. Int J Cardiol. 2018 Jan 1;250:16-20. doi: 10.1016/j.ijcard.2017.08.068. Epub 2017 Sep 8.
PubMed 29031990Ang D, Young R, Taggart D, Carrick D, Chattopadhyay S, Raja Y, Balachandran K, Elghamaz A, Greenwood J, Hoole S, Cotton J, Choudhury A, O'Kane P, Jadhav S, Purcell I, Mitra R, Sabra A, Giblett J, Byrne R, O'Gallagher K, Subkovas E, Rampat R, Anantharam B, Radhakrishnan A, Owens C, Damman P, Guzik B, Collison D, Howarth F, Lennon L, Tolentino PM, Vicere A, Martin K, Kamdar A, Sykes R, Hanna R, Tan D, Heggie R, Wu O, Welsh P, Ford T, Lang CC, Kunadian V, McConnachie A, Berry C. International study of coronary microvascular angina (iCorMicA): A registry-based diagnostic study and nested randomized trial. Am Heart J. 2026 Jul 6;301:107527. doi: 10.1016/j.ahj.2026.107527. Online ahead of print.
PubMed 42409349Ang DTY, Collison DG, McGeoch RJ, Carrick D, Sykes RA, Bradley C, Kamdar AL, Jong A, Brogan RA, MacDougall DA, McCartney PJ, Rocchiccioli JP, Apps AP, Murphy CA, Robertson KE, Shaukat A, Ghattas A, Joshi FR, Sood A, Good RIS, O'Rourke B, Eteiba H, Lindsay MM, McConnachie A, Berry C. Novel Contrast-Derived Indices of Coronary Microvascular Function: Potential Clinical and Cost Benefits. Circ Cardiovasc Interv. 2025 Jun;18(6):e015058. doi: 10.1161/CIRCINTERVENTIONS.124.015058. Epub 2025 May 1.
PubMed 40308206
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- International Study of Coronary Microvascular Angina (iCorMicA): a Randomised, Controlled, Multicentre Trial and Registry
- ClinicalTrials.gov ID
- NCT04674449
- Acronym / sponsor ID
- iCorMicA / GN19CA435
- Conditions
- Microvascular Angina, Angina, Stable, Ischemia With No Obstructive Coronary Arteries (INOCA), Coronary Microvascular Dysfunction (CMD), Ischaemic Heart Disease, Non-Obstructive Coronary Atherosclerosis
- Keywords
- angina, microvascular angina, ischaemia with no obstructive coronary artery disease (INOCA), stratified medicine, clinical trial, outcomes research, prognosis, health economics
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,500 participants (estimated)
- Lead sponsor
- NHS Greater Glasgow and ClydeUniversity, hospital or other
- Collaborators
- University of Glasgow, Abbott Medical Devices
- Study start
- 30 Dec 2020 (actual)
- Primary completion
- 30 Jun 2026 (estimated)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 19 Dec 2020 (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.
The iCorMicA study is a multicentre, prospective, randomised, double-blind, sham-controlled, parallel-group, end-point trial and registry. The investigators seek to determine whether stratified medical therapy guided by an adjunctive interventional diagnostic procedure (IDP) during the invasive management of patients with known or suspected angina but no obstructive coronary artery disease improves symptoms, wellbeing, cardiovascular risk and clinical outcomes.
Detailed description
Ischaemic heart disease (IHD) includes coronary artery disease (or 'coronary heart disease 'CHD') and ischaemic with no obstructive coronary arteries (INOCA). Coronary angiography is standard care for the evaluation of symptomatic patients and known or suspected coronary artery disease. A considerable proportion e.g. >1 in 3, of patients undergoing invasive coronary angiography for known or suspected angina do not have obstructive epicardial coronary artery disease.
The CorMicA pilot study involved prospective enrolment of patients referred for clinically indicated coronary angiography during a 12-month period (2016-2017) in the West of Scotland). 391 patients were enrolled, 185 (47%) had no obstructive coronary disease and 151 were randomised in a clinical trial of stratified medicine based on invasive tests of coronary vascular function. A high proportion (~4 in 5) of these patients had a diagnosis of INOCA due to a disorder of coronary vasomotion including microvascular- and/or vasospastic angina. The trial provided preliminary evidence that stratified medicine, as an adjunct to standard angiography-guided management, has potential to improve symptoms and quality of life. The mechanisms involved changes in diagnosis, treatment and lifestyle measures.
The CorMicA investigators were the first group to introduce stratified medicine for the management of ischaemic heart disease. Limitations of the CorMicA study included the setting (mainly single centre), partial blinding, short-term follow-up (primary outcome at 6 months) and the sample size. Acetylcholine reactivity testing was used to assess the susceptibility to coronary spasm (microvascular and/or macrovascular). Although acetylcholine is a naturally occurring substance, current formulations are not licensed for parenteral administration. Further, clinicians should have training and experience before implementing acetylcholine coronary reactivity testing. These considerations present a barrier to adoption in daily practice, which becomes all the more relevant given INOCA is generally under-recognised. A diagnostic coronary guidewire is already widely used in standard care and, unlike reactivity testing using acetylcholine, a guidewire has transferable potential to support stratified medicine during routine practice. This is especially the case for ad-hoc follow-on testing when obstructive coronary artery disease is excluded.
The vasoactive responses to acetylcholine reflect endothelial and vascular smooth muscle cell effects, which may overlap with the vasoactive responses to adenosine (non-endothelial dependent). Calcium channel blocker therapy is indicated for the functional endotypes associated with impaired vasodilatation and/or vasoconstriction. This raises the possibility that acetylcholine testing may not be routinely required as an adjunctive test to coronary angiography and instead could be reserved for selected cases, or in specialist centres. Instead, the diagnostic guidewire approach may be sufficient as a routine, first line test for the evaluation of INOCA during daily practice.
Anatomical imaging using coronary angiography is the standard of care and clinicians may determine any diagnosis based on all of the available information and their clinical judgement. This approach avoids the need for additional tests. With this approach, the patient's symptoms in response to empirical therapy can be assessed during follow-up and the treatment can be revised as clinically appropriate. In daily practice, adoption of adjunctive tests of coronary function is very low and, in the absence of large, multicentre trials, coronary angiography with or without adjunctive tests of coronary vascular function may be considered reasonable, reflecting equipoise.
iCorMicA is a multicentre, prospective, randomised, double-blind, sham-controlled, parallel-group, end-point (patient reported outcome measures (PROMS), health outcomes, health economics) trial and registry. The investigators aim to determine whether stratified medical therapy, guided by a guidewire-based interventional diagnostic procedure (IDP) at the time of invasive coronary angiography (i.e. functional angiography), improves outcomes in patients with known or suspected angina but no obstructive coronary artery disease. Symptoms of angina or angina-equivalent are determined according to the Rose and/or Seattle Angina questionnaires. The IDP utilises principles of thermodilution to measure coronary vascular function (IMR, CFR, RRR), which aid clinicians in establishing a diagnosis of microvascular angina, vasospastic angina, mixed (both), or none, as per Coronary Vasomotion Disorders International Study Group (COVADIS) criteria. The feasibility, safety, efficacy and effect on healthcare resource utilisation of stratified medicine will be tested in multiple hospitals in different countries in Europe.
Participants with no obstructive epicardial coronary artery disease (coronary stenosis <50% and/or FFR >0.80) are eligible for randomisation (1:1) to either the intervention (IDP-guided, results disclosed) or blinded control (IDP undertaken but results not disclosed, standard of care) group. Medical therapy will be informed according to the clinical diagnosis (endotype). Patients in the intervention group with abnormal coronary vascular function may undergo repeated evaluations to assess the response to intracoronary therapy e.g. calcium channel blocker, enabling a personalised treatment plan. Patients who are ineligible for randomisation (e.g. obstructive coronary artery disease) may be entered into a prospective clinical registry, with individuals from each site invited to undergo similar follow-up assessments as the randomised participants.
Trial participants will be blinded to treatment group. The clinicians responsible for on-going care will also be blinded. Following invasive management, patients and clinicians will be advised of the diagnosis (endotype) but not the randomised group. The endotype will be informed by the IDP in the intervention group but not in the control group (sham procedure). 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 1500 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 measure is the Summary Score of the Seattle Angina Questionnaire at 12 months. 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.
Additional objectives include the wider evaluation of the safety and diagnostic utility of the IDP in a multicentre, multinational setting, and the effects of stratified medicine on the rates of major adverse cardiovascular events by randomised group. The registry will represent a parallel control group. Scientific analyses of circulating biomarkers will be performed to better understand the pathophysiology of INOCA.
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 - Stratified Medicine | Active comparator | Diagnostic Test: Disclosure of IDP resultsAll randomised participants will receive stratified medicine. The subjects will undergo functional coronary angiography involving guidewire-based coronary function tests (interventional diagnostic procedure, IDP) as an adjunct to invasive coronary angiography. The IDP results will be disclosed to the catheter laboratory 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 IDP findings. |
| Standard Care Group | Sham comparator | Other: IDP 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 receive the IDP at time of the angiogram. The results of the IDP will be concealed from the catheter laboratory clinician who will be blinded. The cardiac physiologist / clinical scientist will remain unblinded for the purpose of data recording and quality assurance. The sham procedure is intended to be the same as in the Intervention Group. 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 IDP findings. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age ≥18 years.
- A clinical plan for invasive coronary angiography.
- Symptoms of angina (typical or atypical) according to the Rose- and/or Seattle Angina questionnaires.
- Able to comply with study procedures.
- Able to provide informed consent.
Key exclusion criteria (4 listed)
- A non-coronary primary indication for invasive angiography (e.g. valve disease, heart failure).
- History of coronary artery bypass surgery.
- Presence of obstructive disease evident in a main coronary artery (diameter >2.5 mm), i.e. a coronary stenosis >50% and/or a fractional flow reserve (FFR) ≤0.80*.
- Logistical reason*. *These patients will enter a follow-up registry.
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 |
|---|---|---|
| Disclosure of IDP resultsAlso: Stratified medicineThe results of the adjunctive IDP performed at time of invasive coronary angiography are made available to the catheter laboratory clinician, to aid in the diagnostic process. | Diagnostic test | Intervention Group - Stratified Medicine |
| IDP performed but results not disclosedAlso: Standard, angiography-guided managementThe results of the IDP performed at the time of invasive coronary angiography are concealed from the catheter laboratory clinician who will be blinded. The patient is managed according to standard of care. | Other | Standard Care Group |
Primary outcome
Seattle Angina Questionnaire (SAQ) Summary Score
Time frame: 12 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.
8 secondary outcomes
Feasibility of stratified medicine
Time frame: 0-60 months
Safety of the interventional diagnostic procedure (IDP)
Time frame: 0-60 months
Diagnostic utility of the interventional diagnostic procedure (IDP)
Time frame: 0-60 months
Clinical utility
Time frame: 0-60 months
Health status
Time frame: 0-60 months
Cardiovascular risk
Time frame: 0-60 months
Health outcomes
Time frame: 0 months - 10 years
Health economics
Time frame: 0 months - 10 years
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 9 Apr 2026.
- Background: PubMed 32626906Kunadian 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.
- Background: PubMed 28289007Bairey Merz CN, Pepine CJ, Walsh MN, Fleg JL. Ischemia and No Obstructive Coronary Artery Disease (INOCA): Developing Evidence-Based Therapies and Research Agenda for the Next Decade. Circulation. 2017 Mar 14;135(11):1075-1092. doi: 10.1161/CIRCULATIONAHA.116.024534.
- 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 21911339Jespersen L, Hvelplund A, Abildstrom SZ, Pedersen F, Galatius S, Madsen JK, Jorgensen E, Kelbaek H, Prescott E. Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. Eur Heart J. 2012 Mar;33(6):734-44. doi: 10.1093/eurheartj/ehr331. Epub 2011 Sep 11.
- Background: PubMed 26404197Sara JD, Widmer RJ, Matsuzawa Y, Lennon RJ, Lerman LO, Lerman A. Prevalence of Coronary Microvascular Dysfunction Among Patients With Chest Pain and Nonobstructive Coronary Artery Disease. JACC Cardiovasc Interv. 2015 Sep;8(11):1445-1453. doi: 10.1016/j.jcin.2015.06.017.
- Background: PubMed 31833416Ford 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.
- 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 31504439Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C, Prescott E, Storey RF, Deaton C, Cuisset T, Agewall S, Dickstein K, Edvardsen T, Escaned J, Gersh BJ, Svitil P, Gilard M, Hasdai D, Hatala R, Mahfoud F, Masip J, Muneretto C, Valgimigli M, Achenbach S, Bax JJ; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020 Jan 14;41(3):407-477. doi: 10.1093/eurheartj/ehz425. No abstract available.
- Background: PubMed 29031990Ong P, Camici PG, Beltrame JF, Crea F, Shimokawa H, Sechtem U, Kaski JC, Bairey Merz CN; Coronary Vasomotion Disorders International Study Group (COVADIS). International standardization of diagnostic criteria for microvascular angina. Int J Cardiol. 2018 Jan 1;250:16-20. doi: 10.1016/j.ijcard.2017.08.068. Epub 2017 Sep 8.
- Derived from this study: PubMed 42409349Ang D, Young R, Taggart D, Carrick D, Chattopadhyay S, Raja Y, Balachandran K, Elghamaz A, Greenwood J, Hoole S, Cotton J, Choudhury A, O'Kane P, Jadhav S, Purcell I, Mitra R, Sabra A, Giblett J, Byrne R, O'Gallagher K, Subkovas E, Rampat R, Anantharam B, Radhakrishnan A, Owens C, Damman P, Guzik B, Collison D, Howarth F, Lennon L, Tolentino PM, Vicere A, Martin K, Kamdar A, Sykes R, Hanna R, Tan D, Heggie R, Wu O, Welsh P, Ford T, Lang CC, Kunadian V, McConnachie A, Berry C. International study of coronary microvascular angina (iCorMicA): A registry-based diagnostic study and nested randomized trial. Am Heart J. 2026 Jul 6;301:107527. doi: 10.1016/j.ahj.2026.107527. Online ahead of print.
- Derived from this study: PubMed 40308206Ang DTY, Collison DG, McGeoch RJ, Carrick D, Sykes RA, Bradley C, Kamdar AL, Jong A, Brogan RA, MacDougall DA, McCartney PJ, Rocchiccioli JP, Apps AP, Murphy CA, Robertson KE, Shaukat A, Ghattas A, Joshi FR, Sood A, Good RIS, O'Rourke B, Eteiba H, Lindsay MM, McConnachie A, Berry C. Novel Contrast-Derived Indices of Coronary Microvascular Function: Potential Clinical and Cost Benefits. Circ Cardiovasc Interv. 2025 Jun;18(6):e015058. doi: 10.1161/CIRCINTERVENTIONS.124.015058. Epub 2025 May 1.
- Individual participant dataSharing planned: Yes
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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.
Daniel Ang, MBChB contact
Colin Berry, MBChB, PhD study chair
University of Glasgow
39 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Disclosure of IDP results and IDP performed but results not disclosed in people with Microvascular Angina and Angina, Stable, run by NHS Greater Glasgow and Clyde at 39 sites in 4 countries.
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 5 inclusion and 4 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: looking for participants now, as of the sponsor's last update on 9 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 39 sites in United Kingdom, Ireland, Netherlands, Poland. 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?
Contact Colin Berry, MBChB, PhD (+44 141 330 3325, colin.berry@glasgow.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Seattle Angina Questionnaire (SAQ) Summary Score (time frame: 12 months). 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 NCT04674449, which also lists 11 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 9 Apr 2026; AzTrials last refreshed its copy on 7 Nov 2026.