RecruitingPhase 2NCT05198791

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

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

Sponsor

NHS National Waiting Times Centre Board

Enrollment

400 participants

Start Date

Feb 4, 2022

Study Type

INTERVENTIONAL

Conditions

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

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria4

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.

Exclusion Criteria15

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.

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Interventions

DRUGStratified medicine - Microvascular dysfunction and eplerenone therapy, tablets

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.

OTHERStratification and standard care

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.