Stratified Medicine of Eplerenone in Acute Myocardial Infarction or Injury and no Obstructive Coronary Arteries.

NCT05198791 | Recruiting Phase 2 DMC

• 1 other identifier: 21/CARD/29
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Myocardial Injury; Myocardial Infarction, Acute; Myocardial Infarction With Nonobstructive Coronary Arteries

Keywords

Stratified Medicine; Mineralocorticoid receptor antagonists; MINOCA; Myocardial injury; Myocardial infarction; Myocardial Infarction with Nonobstructive Coronary Arteries

Outcome Measures

Primary Outcomes (1)

• Within patient change in NTproBNP

  NTproBNP will be measured at enrolment, thirty days and six months

  Enrolment, thirty days and six months

Secondary Outcomes (17)

• Major Adverse Cardiovascular and Cerebrovascular Events

  From enrolment to six months (trial) and twenty years (registry and trial)

• Major Adverse Cardiac Events

  From enrolment to six months (trial) and twenty years (registry and trial)

• Adverse ischaemic cardiac events

  From enrolment to six months (trial) and tweny years (registry and trial)

• Left ventricular remodelling at 6 months (MRI)

  Within fourteen days of enrolment and at six months

• Left ventricular systolic function

  Within fourteen days and at six months

Other Outcomes (1)

• Hospital episodes of care for chest pain

  Enrolment to six months (trial) and twenty years (registry and trial)

Study Arms (2)

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.

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.

Other: Stratification and standard care

Interventions

Stratified medicine - Microvascular dysfunction and eplerenone therapy, tablets DRUG

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.

Also known as: Eplerenone

Eplerenone

Stratification and standard care OTHER

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.

Standard of care

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years.
• 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.

You may not qualify if:

• 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 :
• 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.

Sponsors & Collaborators

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

Study Sites (2)

University Hospital Hairmyres

East Kilbride, Lanarkshire, G75 8RG, United Kingdom

RECRUITING

Golden Jubilee National Hospital

Glasgow, United Kingdom

RECRUITING

Related Publications (8)

• 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.

  PMID: 41428430 BACKGROUND

• Berry C, Sykes RA, Tan D. MINOCA: a call for randomized trials. Eur Heart J. 2026 Jan 29:ehaf1075. doi: 10.1093/eurheartj/ehaf1075. Online ahead of print. No abstract available.

  PMID: 41605253 BACKGROUND

• Byrne 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.

  PMID: 37622654 BACKGROUND

• Sykes 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.

  PMID: 34188694 BACKGROUND

• Pelliccia 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.

  PMID: 34087335 BACKGROUND

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

  PMID: 32819476 BACKGROUND

• Bairey 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.

  PMID: 32087007 BACKGROUND

• Ford TJ, Stanley B, Good R, Rocchiccioli P, McEntegart M, Watkins S, Eteiba H, Shaukat A, Lindsay M, Robertson K, Hood S, McGeoch R, McDade R, Yii E, Sidik N, McCartney P, Corcoran D, Collison D, Rush C, McConnachie A, Touyz RM, Oldroyd KG, Berry C. Stratified Medical Therapy Using Invasive Coronary Function Testing in Angina: The CorMicA Trial. J Am Coll Cardiol. 2018 Dec 11;72(23 Pt A):2841-2855. doi: 10.1016/j.jacc.2018.09.006. Epub 2018 Sep 25.

  PMID: 30266608 BACKGROUND

MeSH Terms

Conditions

Myocardial Infarction; MINOCA

Interventions

Tablets; Eplerenone; Standard of Care

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations; Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Colin Berry, PhD

  University of Glasgow

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Colin Berry, PhD

CONTACT

01413303325; colin.berry@glasgow.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants will be masked on their assignment to either the control group vs. registry. Assessors for the primary outcome (laboratory measurement) will be blinded to treatment group assigment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Prospective, randomised, open-label, blinded, end-point (mechanistic, PROBE design).

Study Record Dates

• First Submitted: December 20, 2021
• First Posted: January 20, 2022
• Study Start: February 4, 2022
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: At the end of the study
• Access Criteria: Bon fide research request and sponsor approval.

Locations

GB (2)