Myocardial Infarction, AcutePhase 2StratMedMINOCANCT05198791
Stratified Medicine of Eplerenone in Acute Myocardial Infarction or Injury and no Obstructive Coronary Arteries.
A Phase 2 study testing Stratified medicine - Microvascular dysfunction and eplerenone therapy, tablets in people with Myocardial Infarction, Acute and Myocardial Infarction With Nonobstructive Coronary Arteries, run by NHS National Waiting Times Centre Board at 2 sites in United Kingdom.
Trial summary
Patients with heart attack or heart injury are tested (angiogram) for blockages in their arteries. Patients may develop heart problems caused by damage to small (microvascular) blood vessels. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myocardial Infarction, Acute, Myocardial Infarction With Nonobstructive Coronary Arteries, Myocardial Injury
- What is being tested?
- Stratified medicine - Microvascular dysfunction and eplerenone therapy, tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 400 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 4 Feb 2022to 31 Jul 2026
- Phase
- Phase 2
- 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.
- Acute myocardial infarction or myocardial injury and no obstructive coronary arteries.
- Cardiovascular risk factor (≥1): age >70 years, atrial fibrillation, diabetes, current smoker, eGFR 30 - 60 mL/ minute/1.73 m2, prior MI, treated hypertension or COVID-19 (confirmed or suspected)
- Coronary angiography.
Who cannot join
- Obstructive coronary artery disease
- Left ventricular ejection fraction ≤40% with evidence of heart failure, following myocardial infarction.
- Estimated glomerular filtration rate <30 mL/ minute/1.73 m2
- Severe liver impairment
- Women who are pregnant, breast-feeding or of child-bearing potential (WoCBP) without a negative pregnancy test and who are unwilling or unable to follow the reproductive restrictions defined in the eligibility criteria and use highly effective contraception as defined in Appendix 2 for the duration of the study treatment and 30 days after last dose of study drug.
- Patients taking one of the following medicines :
Show all 15Show fewer
- Pre-existing treatment with an MRA :
- Anti-fungal drugs (ketoconazole or itraconazole).
- Antiviral medication (nelfinavir or ritonavir).
- Antibiotics (clarithromycin or telithromycin).
- Nefazodone used to treat depression.
- The combination of an angiotensin converting enzyme (ACE) inhibitor and an angiotensin receptor blocker (ARB)) together.
- Contra-indication to cardiovascular magnetic resonance imaging e.g. severe claustrophobia, metallic foreign body.
- Contra-indication to intravenous adenosine, i.e. severe asthma; long QT syndrome; second- or third-degree atrio-ventricular block and sick sinus syndrome.
- Lack of informed consent.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom2 sites, 2 recruiting
- Recruiting
University Hospital Hairmyres
East Kilbride, Lanarkshire, G75 8RG
David Carrick, MBChB PhD, 01355 585 000, david.carrick@lanarkshire.scot.nhs.uk
- Recruiting
Golden Jubilee National Hospital
Glasgow
Colin Berry, PhD, 01419515000, colin.berry@glasgow.ac.uk
Robert A Sykes, MBChB
About this study
Official title: The Effect of Mineralocorticoid Receptor Antagonist Therapy in Patients With Acute Myocardial Infection or Injury and no Obstructive Coronary Arteries: a Registry-based, Stratified-medicine, Randomized, Controlled Trial
Patients with heart attack or heart injury are tested (angiogram) for blockages in their arteries. Patients may develop heart problems caused by damage to small (microvascular) blood vessels. Eplerenone, a mineralocorticoid receptor-selective antagonist, reduces blood vessel injury and is used to treat high blood pressure and heart failure.
Aim: to test the use of eplerenone in patients with heart attack/heart injury an no obstructive coronary arteries and small vessel problems (coronary microvascular dysfunction).
Read more
Patients admitted to hospitals in the West of Scotland (2.5 million) and referred for invasive management to the Golden Jubilee and Hairmyres hospitals because of a suspected heart attack heart will be invited to participate into a registry-based clinical trial. Screening, enrolment and verbal, informed consent will be obtained during the angiogram then written consent on the ward. Small vessel disease will be assessed using a 'diagnostic' guidewire during the standard angiogram. People with small vessel problems will be invited to participate in a clinical trial of usual care or eplerenone. Coronary microvascular dysfunction is defined as an index of microvascular resistance ≥25. Coronary flow reserve (CFR abnormal <2.0), microvascular resistance reserve ratio (MRR, abnormal <2.5), and resistance reserve ratio (RRR abnormal <2.0), measured simultaneously with IMR, are predefined parameters of interest.
Patients will be allocated into one of the 3 groups:
- Group 1: Patients without coronary microvascular dysfunction. No eplerenone
- Group 2: Patient with coronary microvascular dysfunction. Usual care, no eplerenone.
- Group 3: Small vessels abnormal. Eplerenone tablets.
The primary outcome for the trial will be reduced heart injury (biomarkers) in patients with microvascular disease. We will also test heart function (MRI scan) at enrolment and at six months. All patients (Groups 1, 2 and 3) will have an angiogram. Standard blood tests will be collected during the hospital stay, and then again at 1 and 6 months. Other outcomes include questionnaires (health status). We will gather information on longer-term health outcomes (hospitalisation, death) using confidential electronic record linkage. We will ask for permission to store blood samples for future research.
The research will improve scientific knowledge about eplerenone therapy in this patient group. The study will create a repository of clinical samples and images which will provide vital data for studies of endotypes of myocardial infarction or injury with no obstructive coronary arteries.
Read the detailed description
Background: Myocardial infarction with non-obstructive coronary arteries (MINOCA) involves vascular dysfunction, prognosis is impaired and specific treatments are lacking. Mineralocorticoid antagonist (MRA) therapy attenuates left ventricular remodelling in patients with acute MI without heart failure e.g. REMINDER trial.
Stratified medicine is defined by the Medical Research Council Framework (2015) as the identification of key sub-groups of patients within a heterogeneous population; these being distinguishable groups with differing mechanisms of disease, or particular responses to treatments. Stratification can be used to improve mechanistic understanding of disease processes and enable: the identification of new targets for treatments; the development of biomarkers for disease risk, diagnosis, progression and response to treatment; and treatments to be tested and applied in the most appropriate patient groups.
Objective: To implement stratified medicine in MINOCA and nonischemic myocardial injury.
Primary Hypothesis of the registry-based diagnostic study: In patients with suspected MINOCA, elevated coronary microvascular resistance defined by index of microvascular resistance ≥25 mmHg·s, is common and quantifiable, identifying a clinically relevant endotype suitable for stratified care.
Primary hypothesis (Trial): In patients with an initial working diagnosis of MINOCA, early risk stratification by coronary microvascular dysfunction (index of microvascular resistance (IMR) ≥25) coupled with cardio-protective MRA therapy using eplerenone limits myocardial damage reflected by changes in N-terminal (NT)-pro hormone BNP (NT-proBNP).
Secondary hypotheses for predefined mechanistic, clinical and exploratory outcomes in the registry and nested, randomised trial will also be explored.
Overall aim: To undertake a developmental clinical study, clarify evidence-gaps and provide training in academic cardiology.
Design A prospective, registry-based, diagnostic study and nested, randomized, open-label, blinded-endpoint (PROBE) basket trial .
The registry involves a prospective diagnostic study with the aims of endotyping patients through a standardized protocol of invasive and non-invasive diagnostic evaluations. The nested randomized trial evaluates stratified therapy with eplerenone in patients with invasive evidence of coronary microvascular dysfunction, defined as IMR (≥25), and no demonstrable alternative non-ischemic etiology.
Procedures Step-1: Screening in during coronary angiography of patients with acute myocardial infarction including suspected MINOCA without heart failure or left ventricular ejection fraction ≤40%; Step-2: Guidewire-based measurement of microvascular resistance (culprit artery or if unknown, the left anterior descending coronary artery. Registry population, n=300); Step-3: Stratify subgroup with -increased vascular risk (IMR≥25) (Trial, n=150 eligible for MRA, informed consent); Step-4: Randomise this higher-risk group: eplerenone 25-50 mg daily for 6 months or standard care. Coronary physiology parameters including coronary flow reserve (CFR abnormal <2.0), microvascular resistance reserve ratio (MRR, abnormal <2.5), the resistance reserve ratio (RRR abnormal <2.0) and left ventricular end-diastolic pressure will be prospectively measured during the index invasive procedure. A diagnostic algorithm will be followed in line with the 2023 Acute Coronary Syndrome guidelines of the European Society of Cardiology (PMID: 37622654). Cardiovascular magnetic resonance (CMR) imaging (MRI) will be undertaken as soon as possible after diagnosis. For participants who are straified for participation in the randomized trial, CMR imaging with adenosine stress/rest myocardial perfusion imaging will be undertaken at 6-months. They will also be invited to participate in a brain MRI substudy ('heart-brain') including to assess for systemic features of small vesel disease.
Outcomes: Primary: within-subject change in NT-proBNP by group; Secondary: left ventricular ejection fraction; left ventricular volumes; patient reported outcome measures (PROMS).
Value: Evidence-synthesis on stratified medicine for MINOCA.
In order to assess the natural history of clinical endotypes, and effects of the trial intervention, electronic health record linkage of vital status, episodes of healthcare and medication use will be assessed during follow-up of up to 20-years. The study design has benefitted from patient and public involvement (PPI). The study is overseen by a Trial Steering Committee including an indendent Chair, a lived experience representative, a sponsor representative and the lead investigators.
- Conditions
- Myocardial Infarction, Acute, Myocardial Infarction With Nonobstructive Coronary Arteries, Myocardial Injury
- Being tested
- Stratified medicine - Microvascular dysfunction and eplerenone therapy, tablets, Stratification and standard care
- Keywords
- Stratified Medicine, Mineralocorticoid receptor antagonists, MINOCA, Myocardial injury, Myocardial infarction, Myocardial Infarction with Nonobstructive Coronary Arteries
- Medical subject headings
- Myocardial Infarction, MINOCA
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stratified medicine - Microvascular dysfunction and eplerenone therapy, tabletsDrug
Also called Eplerenone
Stratified medicine including interventional diagnostic procedure (IDP) and linked treatment with eplerenone. Patients with an increased IMR (strata with microvascular dysfunction, IMR ≥25) will be eligible for randomization to this arm. Patients randomized to receive eplerenone will be commenced on 25 mg once daily, and uptitrated to 50 mg once daily after two weeks. Treatment will be continued for a period of six months.
Stratification and standard careOther
Interventional diagnostic procedure (IDP) without linked treatment i.e., standard care. Patients with an increased IMR (strata with microvascular dysfunction, IMR ≥25) will be eligible for randomization to this arm. In the standard care group, the IDP is performed but the results are not disclosed. The IDP is therefore a sham procedure. Patients randomized to receive eplerenone will be commenced on 25 mg once daily, and uptitrated to 50 mg once daily after two weeks. Treatment will be continued for a period of six months.
| Study group | Role | What they receive |
|---|---|---|
| Eplerenone | Experimental | Patients with suspected MINOCA and an index of microvascular resistance (IMR) greater than or equal to 25 will be randomised to receive eplerenone (starting dose 25 mg, uptitrated to 50 mg after two weeks) for six months or standard of care and research protocol study visits. Patients who are screened, give informed consent but are not randomized will enter a followup registry. Receives: Drug: Stratified medicine - Microvascular dysfunction and eplerenone therapy, tablets |
| Standard of care | Sham comparator | Patients with suspected MINOCA and an index of microvascular resistance (IMR) greater than or equal to 25 will be randomised to receive eplerenone (starting dose 25 mg, uptitrated to 50 mg after two weeks) for six months or standard of care and research protocol study visits. Patients who are screened, give informed consent but are not randomized will enter a followup registry. Receives: Other: Stratification and standard care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Within patient change in NTproBNP
NTproBNP will be measured at enrolment, thirty days and six months
Measured: Enrolment, thirty days and six months
Secondary outcomes (17)
Major Adverse Cardiovascular and Cerebrovascular Events
Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) defined as cardiovascular death, resuscitated cardiac arrest, and hospitalisation for non-fatal myocardial infarction, angina, heart failure, atrial fibrillation/atrial flutter, stroke or transient ischaemic attack. These are spontaneous adverse cardiovascular events.
Measured: From enrolment to six months (trial) and twenty years (registry and trial)
Major Adverse Cardiac Events
Major Adverse Cardiac Events (Cardiac MACE) including cardiac death, non-fatal myocardial infarction or hospitalization for heart failure.
Measured: From enrolment to six months (trial) and twenty years (registry and trial)
Adverse ischaemic cardiac events
Adverse ischaemic cardiac events (AICE) defined as cardiac death, resuscitated cardiac arrest, hospitalisation for myocardial infarction, or hospital episode of unscheduled care for angina with or without admission.
Measured: From enrolment to six months (trial) and tweny years (registry and trial)
Left ventricular remodelling at 6 months (MRI)
Cardiac MRI performed within fourteen days of enrolment and at six months
Measured: Within fourteen days of enrolment and at six months
Left ventricular systolic function
Left ventricular systolic function reflected by left ventricular ejection fraction (%) measured by cardiac magnetic resonance imaging (MRI).
Measured: Within fourteen days and at six months
Myocardial blood flow at 6 months (MRI)
Cardiac MRI with adenosine stress perfusion to measure myocardial blood flow (ml/min/g tissue) at rest and during adenosine-induced hypereremia and myocardial perfusion reserve.
Measured: Performed at six months
Myocardial extracellular volume fraction
Myocardial extracellular volume fraction (ECV) quantified by cardiovascular magnetic resonance imaging
Measured: Within fourteen days and at six months
Health-related quality of life, patient-assessed
European Quality of Life 5-domain 5-Level (EQ-5D-5L) questionnaire, a patient reported outcome measure. Patient assessed score - Scale 0 (worst), 100 (best)
Measured: Enrolment, thirty days and six months
Health economics
Institute for Medical Technology Assessment Productivity Cost Questionnaire (iPCQ)
Measured: Enrolment, thirty days and six months
Illness perception
Brief Illness Perception Questionnaire (B-IPQ). Higher scores indicate a higher perceived threat with regard to the illness.
Measured: Enrolment, thirty days and six months
Anxiety and depression
Patient Health Questionnaire-4 (PHQ-4). A higher score reflects greater anxiety and depression
Measured: Enrolment, thirty days and six months
Functional capacity
Duke Activity Status Index (DASI). A higher total score indicates better functional and aerobic capacity.
Measured: Enrolment, thirty days and six months
Physical activity
International Physical Activity Questionnaire Short Form (IPAQ-SF), estimated in Metabolic Equivalent of Tasks (METS)
Measured: Enrolment, thirty days and six months
Cognitive function
Montreal Cognitive Assessment (MoCA). A score of 26 or higher is considered is normal. A score below 26 may indicate mild cognitive impairment.
Measured: Enrolment, thirty days and six months
Fibrosis
Circulating (plasma) concentration of procollagen type-I C-terminal pro-peptide (PICP) and collagen type-1 C-terminal telopeptide (CITP) reflect synthesis and degradation of type-I collagen and PICP/CITP ratio reflects collagen turnover.
Measured: Enrolment, thirty days and six months
Haemostasis pathway activation
Circulating (plasma) concentration of factor VIII and other biomarkers of haemostasis pathway activation e.g. D-dimers, fibrinogen
Measured: Enrolment, thirty days and six months
Biomarkers of vascular inflammation
Vascular cell adhesion molecule (VCAM) is a biological marker of vascular inflammation. VCAM will be measured at enrolment, thirty days and six months
Measured: Enrolment, thirty days and six months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2022
- Study start4 Feb 2022
- Primary completion31 Jul 2026 (estimated)
- Study completion31 Jul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Myocardial Infarction, AcuteStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective, randomised, open-label, blinded, end-point (mechanistic, PROBE design).
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NHS National Waiting Times Centre Board
- Sponsor type
- University, hospital or other
- Collaborators
- British Heart Foundation, Abbott
- Responsible party
- Principal investigator, Colin Berry, NHS National Waiting Times Centre Board
- Investigators
- Colin Berry, PhD, Principal investigator, University of Glasgow
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05198791
- Sponsor's protocol ID
- 21/CARD/29
- Acronym
- StratMedMINOCA
- Status last verified
- Mar 2026
- First submitted
- 20 Dec 2021
- Last updated
- 16 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be shared based on a bon fide research request and sponsor approval.
Publications
Morrone D, Stefanini G, De Carlo M, Giannini C, Toth G, Prunea D, Zivelonghi C, Benedetti A, De Bruyne B, Wilgenhof A, Kanovsky J, Kala P, Holmvang L, Hasbak M, Hildick-Smith D, Cockburn J, Amabile N, Veugeois A, Hovasse T, Neylon A, Honton B, Farah B, Gori T, Knorr M, Wolf A, Schmit T, Hausleiter J, K KS, Abdel-Waha M, Feistritzer HJ, Woitek F, Linke A, Leick J, Afzal S, Alexopoulos D, Varlamos C, Tsioufis K, Dimitriadis K, Testa L, Squillace M, Conrotto F, D'Ascenzo F, Campo G, Cocco M, Di Mario C, Caniato F, Ribichini FL, Prati D, Tarantini G, Cardaioli F, Burzotta F, Paraggio L, Bedogni F, Arzuffi L, Chieffo A, Ghizzoni G, Davidavicius G, Budrys P, Van Mieghem N, Daemen J, Brinkmann R, Bante H, Lesiak M, Iwanczyk S, Pregowski J, Skowronski J, Madeira S, Raposo L, Estevez-Loureiro R, Sisinni A, Escaned J, Jeronimo A, Moreno R, Jimenez-Valero S, Vriesendorp P, Pustjens T, Van Geuns R, Damman P, Van de Hoef T, Van der Harst P, Mamas MA, Duckett S, Mikhail G, Lucarelli C, Berry C, De Caterina R. Myocardial infarction with nonobstructive coronary arteries - the European PERspective (SNIPER) survey. J Cardiovasc Med (Hagerstown). 2025 Dec 1;26(12):731-740. doi: 10.2459/JCM.0000000000001808. Epub 2025 Dec 5.
PubMed 41428430Berry C, Sykes RA, Tan D. MINOCA: a call for randomized trials. Eur Heart J. 2026 Mar 24;47(12):1467-1469. doi: 10.1093/eurheartj/ehaf1075. No abstract available.
PubMed 41605253Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, Chieffo A, Claeys MJ, Dan GA, Dweck MR, Galbraith M, Gilard M, Hinterbuchner L, Jankowska EA, Juni P, Kimura T, Kunadian V, Leosdottir M, Lorusso R, Pedretti RFE, Rigopoulos AG, Rubini Gimenez M, Thiele H, Vranckx P, Wassmann S, Wenger NK, Ibanez B; ESC Scientific Document Group. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023 Oct 12;44(38):3720-3826. doi: 10.1093/eurheartj/ehad191. No abstract available.
PubMed 37622654Sykes R, Doherty D, Mangion K, Morrow A, Berry C. What an Interventionalist Needs to Know About MI with Non-obstructive Coronary Arteries. Interv Cardiol. 2021 Jun 10;16:e10. doi: 10.15420/icr.2021.10. eCollection 2021 Apr.
PubMed 34188694Pelliccia F, Pepine CJ, Berry C, Camici PG. The role of a comprehensive two-step diagnostic evaluation to unravel the pathophysiology of MINOCA: A review. Int J Cardiol. 2021 Aug 1;336:1-7. doi: 10.1016/j.ijcard.2021.05.045. Epub 2021 Jun 1.
PubMed 34087335Ford 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.
PubMed 32819476Bairey Merz CN, Pepine CJ, Shimokawa H, Berry C. Treatment of coronary microvascular dysfunction. Cardiovasc Res. 2020 Mar 1;116(4):856-870. doi: 10.1093/cvr/cvaa006.
PubMed 32087007Ford 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 30266608
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Mineralocorticoid Receptor Antagonist Therapy in Patients With Acute Myocardial Infection or Injury and no Obstructive Coronary Arteries: a Registry-based, Stratified-medicine, Randomized, Controlled Trial
- ClinicalTrials.gov ID
- NCT05198791
- Acronym / sponsor ID
- StratMedMINOCA / 21/CARD/29
- Conditions
- Myocardial Infarction, Acute, Myocardial Infarction With Nonobstructive Coronary Arteries, Myocardial Injury
- Keywords
- Stratified Medicine, Mineralocorticoid receptor antagonists, MINOCA, Myocardial injury, Myocardial infarction, Myocardial Infarction with Nonobstructive Coronary Arteries
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- NHS National Waiting Times Centre BoardUniversity, hospital or other
- Collaborators
- British Heart Foundation, Abbott
- Study start
- 4 Feb 2022 (actual)
- Primary completion
- 31 Jul 2026 (estimated)
- Study completion
- 31 Jul 2026 (estimated)
- First posted
- 20 Jan 2022 (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.
Patients with heart attack or heart injury are tested (angiogram) for blockages in their arteries. Patients may develop heart problems caused by damage to small (microvascular) blood vessels. Eplerenone, a mineralocorticoid receptor-selective antagonist, reduces blood vessel injury and is used to treat high blood pressure and heart failure.
Aim: to test the use of eplerenone in patients with heart attack/heart injury an no obstructive coronary arteries and small vessel problems (coronary microvascular dysfunction).
Patients admitted to hospitals in the West of Scotland (2.5 million) and referred for invasive management to the Golden Jubilee and Hairmyres hospitals because of a suspected heart attack heart will be invited to participate into a registry-based clinical trial. Screening, enrolment and verbal, informed consent will be obtained during the angiogram then written consent on the ward. Small vessel disease will be assessed using a 'diagnostic' guidewire during the standard angiogram. People with small vessel problems will be invited to participate in a clinical trial of usual care or eplerenone. Coronary microvascular dysfunction is defined as an index of microvascular resistance ≥25. Coronary flow reserve (CFR abnormal <2.0), microvascular resistance reserve ratio (MRR, abnormal <2.5), and resistance reserve ratio (RRR abnormal <2.0), measured simultaneously with IMR, are predefined parameters of interest.
Patients will be allocated into one of the 3 groups:
- Group 1: Patients without coronary microvascular dysfunction. No eplerenone
- Group 2: Patient with coronary microvascular dysfunction. Usual care, no eplerenone.
- Group 3: Small vessels abnormal. Eplerenone tablets.
The primary outcome for the trial will be reduced heart injury (biomarkers) in patients with microvascular disease. We will also test heart function (MRI scan) at enrolment and at six months. All patients (Groups 1, 2 and 3) will have an angiogram. Standard blood tests will be collected during the hospital stay, and then again at 1 and 6 months. Other outcomes include questionnaires (health status). We will gather information on longer-term health outcomes (hospitalisation, death) using confidential electronic record linkage. We will ask for permission to store blood samples for future research.
The research will improve scientific knowledge about eplerenone therapy in this patient group. The study will create a repository of clinical samples and images which will provide vital data for studies of endotypes of myocardial infarction or injury with no obstructive coronary arteries.
Detailed description
Background: Myocardial infarction with non-obstructive coronary arteries (MINOCA) involves vascular dysfunction, prognosis is impaired and specific treatments are lacking. Mineralocorticoid antagonist (MRA) therapy attenuates left ventricular remodelling in patients with acute MI without heart failure e.g. REMINDER trial.
Stratified medicine is defined by the Medical Research Council Framework (2015) as the identification of key sub-groups of patients within a heterogeneous population; these being distinguishable groups with differing mechanisms of disease, or particular responses to treatments. Stratification can be used to improve mechanistic understanding of disease processes and enable: the identification of new targets for treatments; the development of biomarkers for disease risk, diagnosis, progression and response to treatment; and treatments to be tested and applied in the most appropriate patient groups.
Objective: To implement stratified medicine in MINOCA and nonischemic myocardial injury.
Primary Hypothesis of the registry-based diagnostic study: In patients with suspected MINOCA, elevated coronary microvascular resistance defined by index of microvascular resistance ≥25 mmHg·s, is common and quantifiable, identifying a clinically relevant endotype suitable for stratified care.
Primary hypothesis (Trial): In patients with an initial working diagnosis of MINOCA, early risk stratification by coronary microvascular dysfunction (index of microvascular resistance (IMR) ≥25) coupled with cardio-protective MRA therapy using eplerenone limits myocardial damage reflected by changes in N-terminal (NT)-pro hormone BNP (NT-proBNP).
Secondary hypotheses for predefined mechanistic, clinical and exploratory outcomes in the registry and nested, randomised trial will also be explored.
Overall aim: To undertake a developmental clinical study, clarify evidence-gaps and provide training in academic cardiology.
Design A prospective, registry-based, diagnostic study and nested, randomized, open-label, blinded-endpoint (PROBE) basket trial .
The registry involves a prospective diagnostic study with the aims of endotyping patients through a standardized protocol of invasive and non-invasive diagnostic evaluations. The nested randomized trial evaluates stratified therapy with eplerenone in patients with invasive evidence of coronary microvascular dysfunction, defined as IMR (≥25), and no demonstrable alternative non-ischemic etiology.
Procedures Step-1: Screening in during coronary angiography of patients with acute myocardial infarction including suspected MINOCA without heart failure or left ventricular ejection fraction ≤40%; Step-2: Guidewire-based measurement of microvascular resistance (culprit artery or if unknown, the left anterior descending coronary artery. Registry population, n=300); Step-3: Stratify subgroup with -increased vascular risk (IMR≥25) (Trial, n=150 eligible for MRA, informed consent); Step-4: Randomise this higher-risk group: eplerenone 25-50 mg daily for 6 months or standard care. Coronary physiology parameters including coronary flow reserve (CFR abnormal <2.0), microvascular resistance reserve ratio (MRR, abnormal <2.5), the resistance reserve ratio (RRR abnormal <2.0) and left ventricular end-diastolic pressure will be prospectively measured during the index invasive procedure. A diagnostic algorithm will be followed in line with the 2023 Acute Coronary Syndrome guidelines of the European Society of Cardiology (PMID: 37622654). Cardiovascular magnetic resonance (CMR) imaging (MRI) will be undertaken as soon as possible after diagnosis. For participants who are straified for participation in the randomized trial, CMR imaging with adenosine stress/rest myocardial perfusion imaging will be undertaken at 6-months. They will also be invited to participate in a brain MRI substudy ('heart-brain') including to assess for systemic features of small vesel disease.
Outcomes: Primary: within-subject change in NT-proBNP by group; Secondary: left ventricular ejection fraction; left ventricular volumes; patient reported outcome measures (PROMS).
Value: Evidence-synthesis on stratified medicine for MINOCA.
In order to assess the natural history of clinical endotypes, and effects of the trial intervention, electronic health record linkage of vital status, episodes of healthcare and medication use will be assessed during follow-up of up to 20-years. The study design has benefitted from patient and public involvement (PPI). The study is overseen by a Trial Steering Committee including an indendent Chair, a lived experience representative, a sponsor representative and the lead investigators.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Prospective, randomised, open-label, blinded, end-point (mechanistic, PROBE design).
| Arm | Type | Receives |
|---|---|---|
| Eplerenone | Experimental | Drug: Stratified medicine - Microvascular dysfunction and eplerenone therapy, tabletsPatients with suspected MINOCA and an index of microvascular resistance (IMR) greater than or equal to 25 will be randomised to receive eplerenone (starting dose 25 mg, uptitrated to 50 mg after two weeks) for six months or standard of care and research protocol study visits. Patients who are screened, give informed consent but are not randomized will enter a followup registry. |
| Standard of care | Sham comparator | Other: Stratification and standard carePatients with suspected MINOCA and an index of microvascular resistance (IMR) greater than or equal to 25 will be randomised to receive eplerenone (starting dose 25 mg, uptitrated to 50 mg after two weeks) for six months or standard of care and research protocol study visits. Patients who are screened, give informed consent but are not randomized will enter a followup registry. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age ≥18 years.
- Acute myocardial infarction or myocardial injury and no obstructive coronary arteries.
- Cardiovascular risk factor (≥1): age >70 years, atrial fibrillation, diabetes, current smoker, eGFR 30 - 60 mL/ minute/1.73 m2, prior MI, treated hypertension or COVID-19 (confirmed or suspected)
- Coronary angiography.
Key exclusion criteria (15 listed)
- Obstructive coronary artery disease
- Left ventricular ejection fraction ≤40% with evidence of heart failure, following myocardial infarction.
- Estimated glomerular filtration rate <30 mL/ minute/1.73 m2
- Severe liver impairment
- Women who are pregnant, breast-feeding or of child-bearing potential (WoCBP) without a negative pregnancy test and who are unwilling or unable to follow the reproductive restrictions defined in the eligibility criteria and use highly effective contraception as defined in Appendix 2 for the duration of the study treatment and 30 days after last dose of study drug.
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 |
|---|---|---|
| Stratified medicine - Microvascular dysfunction and eplerenone therapy, tabletsAlso: EplerenoneStratified medicine including interventional diagnostic procedure (IDP) and linked treatment with eplerenone. Patients with an increased IMR (strata with microvascular dysfunction, IMR ≥25) will be eligible for randomization to this arm. Patients randomized to receive eplerenone will be commenced on 25 mg once daily, and uptitrated to 50 mg once daily after two weeks. Treatment will be continued for a period of six months. | Drug | Eplerenone |
| Stratification and standard careInterventional diagnostic procedure (IDP) without linked treatment i.e., standard care. Patients with an increased IMR (strata with microvascular dysfunction, IMR ≥25) will be eligible for randomization to this arm. In the standard care group, the IDP is performed but the results are not disclosed. The IDP is therefore a sham procedure. Patients randomized to receive eplerenone will be commenced on 25 mg once daily, and uptitrated to 50 mg once daily after two weeks. Treatment will be continued for a period of six months. | Other | Standard of care |
Primary outcome
Within patient change in NTproBNP
Time frame: Enrolment, thirty days and six months
NTproBNP will be measured at enrolment, thirty days and six months
17 secondary outcomes
Major Adverse Cardiovascular and Cerebrovascular Events
Time frame: From enrolment to six months (trial) and twenty years (registry and trial)
Major Adverse Cardiac Events
Time frame: From enrolment to six months (trial) and twenty years (registry and trial)
Adverse ischaemic cardiac events
Time frame: From enrolment to six months (trial) and tweny years (registry and trial)
Left ventricular remodelling at 6 months (MRI)
Time frame: Within fourteen days of enrolment and at six months
Left ventricular systolic function
Time frame: Within fourteen days and at six months
Myocardial blood flow at 6 months (MRI)
Time frame: Performed at six months
Myocardial extracellular volume fraction
Time frame: Within fourteen days and at six months
Health-related quality of life, patient-assessed
Time frame: Enrolment, thirty days and six months
Health economics
Time frame: Enrolment, thirty days and six months
Illness perception
Time frame: Enrolment, thirty days and six months
Anxiety and depression
Time frame: Enrolment, thirty days and six months
Functional capacity
Time frame: Enrolment, thirty days and six months
Physical activity
Time frame: Enrolment, thirty days and six months
Cognitive function
Time frame: Enrolment, thirty days and six months
Fibrosis
Time frame: Enrolment, thirty days and six months
Haemostasis pathway activation
Time frame: Enrolment, thirty days and six months
Biomarkers of vascular inflammation
Time frame: Enrolment, thirty days and six 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 16 Mar 2026.
- Background: PubMed 41428430Morrone D, Stefanini G, De Carlo M, Giannini C, Toth G, Prunea D, Zivelonghi C, Benedetti A, De Bruyne B, Wilgenhof A, Kanovsky J, Kala P, Holmvang L, Hasbak M, Hildick-Smith D, Cockburn J, Amabile N, Veugeois A, Hovasse T, Neylon A, Honton B, Farah B, Gori T, Knorr M, Wolf A, Schmit T, Hausleiter J, K KS, Abdel-Waha M, Feistritzer HJ, Woitek F, Linke A, Leick J, Afzal S, Alexopoulos D, Varlamos C, Tsioufis K, Dimitriadis K, Testa L, Squillace M, Conrotto F, D'Ascenzo F, Campo G, Cocco M, Di Mario C, Caniato F, Ribichini FL, Prati D, Tarantini G, Cardaioli F, Burzotta F, Paraggio L, Bedogni F, Arzuffi L, Chieffo A, Ghizzoni G, Davidavicius G, Budrys P, Van Mieghem N, Daemen J, Brinkmann R, Bante H, Lesiak M, Iwanczyk S, Pregowski J, Skowronski J, Madeira S, Raposo L, Estevez-Loureiro R, Sisinni A, Escaned J, Jeronimo A, Moreno R, Jimenez-Valero S, Vriesendorp P, Pustjens T, Van Geuns R, Damman P, Van de Hoef T, Van der Harst P, Mamas MA, Duckett S, Mikhail G, Lucarelli C, Berry C, De Caterina R. Myocardial infarction with nonobstructive coronary arteries - the European PERspective (SNIPER) survey. J Cardiovasc Med (Hagerstown). 2025 Dec 1;26(12):731-740. doi: 10.2459/JCM.0000000000001808. Epub 2025 Dec 5.
- Background: PubMed 41605253Berry C, Sykes RA, Tan D. MINOCA: a call for randomized trials. Eur Heart J. 2026 Mar 24;47(12):1467-1469. doi: 10.1093/eurheartj/ehaf1075. No abstract available.
- Background: PubMed 37622654Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, Chieffo A, Claeys MJ, Dan GA, Dweck MR, Galbraith M, Gilard M, Hinterbuchner L, Jankowska EA, Juni P, Kimura T, Kunadian V, Leosdottir M, Lorusso R, Pedretti RFE, Rigopoulos AG, Rubini Gimenez M, Thiele H, Vranckx P, Wassmann S, Wenger NK, Ibanez B; ESC Scientific Document Group. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023 Oct 12;44(38):3720-3826. doi: 10.1093/eurheartj/ehad191. No abstract available.
- Background: PubMed 34188694Sykes R, Doherty D, Mangion K, Morrow A, Berry C. What an Interventionalist Needs to Know About MI with Non-obstructive Coronary Arteries. Interv Cardiol. 2021 Jun 10;16:e10. doi: 10.15420/icr.2021.10. eCollection 2021 Apr.
- Background: PubMed 34087335Pelliccia F, Pepine CJ, Berry C, Camici PG. The role of a comprehensive two-step diagnostic evaluation to unravel the pathophysiology of MINOCA: A review. Int J Cardiol. 2021 Aug 1;336:1-7. doi: 10.1016/j.ijcard.2021.05.045. Epub 2021 Jun 1.
- Background: PubMed 32819476Ford 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.
- Background: PubMed 32087007Bairey Merz CN, Pepine CJ, Shimokawa H, Berry C. Treatment of coronary microvascular dysfunction. Cardiovasc Res. 2020 Mar 1;116(4):856-870. doi: 10.1093/cvr/cvaa006.
- 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.
- Individual participant dataSharing planned: Yes. Data will be shared based on a bon fide research request and sponsor approval.
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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.
Colin Berry, PhD principal investigator
University of Glasgow
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Stratified medicine - Microvascular dysfunction and eplerenone therapy, tablets in people with Myocardial Infarction, Acute and Myocardial Infarction With Nonobstructive Coronary Arteries, run by NHS National Waiting Times Centre Board at 2 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 4 inclusion and 15 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 16 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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, PhD (01413303325, 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?
Within patient change in NTproBNP (time frame: Enrolment, thirty days and six 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 NCT05198791, which also lists 8 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 16 Mar 2026.