Evaluation of Ranolazine for the Prevention of Coronary Microvascular Dysfunction in ST-Elevation Myocardial Infarction with Multivessel Disease

Trial ID: 2025-520801-12-00
Protocol: INAMICRON
Sponsor: Universita' Degli Studi Di Napoli Federico II

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Diseases & Conditions

Acute myocardial infarction

Objectives

The primary objective of this study is to evaluate the efficacy of late sodium current inhibition to preserve coronary microcirculation following ST-elevation myocardial infarction in patients with multivessel disease. 5

The secondary objectives include:

Reduction in the prevalence of coronary microvascular dysfunction following successful percutaneous coronary intervention.
Reduction in infarct size as assessed by cardiac magnetic resonance.
Reduction in the prevalence and incidence of coronary microvascular dysfunction in the non-culprit vessel before and after staged percutaneous coronary intervention.
Reduction in the incidence of periprocedural myocardial infarction.
Reduction in the incidence of endothelial dysfunction.
Reduction in the early incidence of major adverse cardiovascular events.
Improvement in angina symptoms and quality of life.

Participants

The sponsor did not provide information regarding the total number of participants. The study population consists of patients experiencing an acute myocardial infarction characterized by ST-elevation myocardial infarction (STEMI) and multivessel disease. Participants include both males and females within the age range of 18 to 79 years. Inclusion requires a history of successful primary percutaneous coronary intervention (pPCI) with TIMI flow grade 3 and residual coronary stenosis of less than 30%. Additionally, the presence of at least one remaining angiographically significant non-culprit stenosis greater than 50% diameter stenosis that is treatable via PCI is required. Women of child-bearing potential must demonstrate post-menopausal status or provide a negative pregnancy test.

Plans and Procedures

This multicenter, randomized, controlled, and open-label Phase IIb clinical trial evaluates the efficacy of late sodium current (INa) inhibition to preserve coronary microcirculation in patients with ST-elevation myocardial infarction and multivessel disease. Participants are assigned to receive oral ranolazine at doses of 1000 mg or 1500 mg. The methodology includes a baseline assessment following successful percutaneous coronary intervention (pPCI) to evaluate index myocardial infarction parameters. The primary endpoint involves measuring the index myocardial resistance (IMR) and/or angioIMR at baseline and during staged revascularization of non-culprit stenoses, occurring either 5 days or within 6 weeks after pPCI. Secondary endpoints include the assessment of coronary microvascular dysfunction, infarct size via cardiac magnetic resonance, endothelial function, and the incidence of major adverse cardiovascular events (MACE). Study involvement extends through follow-up assessments of angina symptoms and quality of life using validated questionnaires. The trial is estimated to occur between October 2025 and October 2027.

Treatment

The experimental intervention involves the administration of ranolazine. This substance is administered via the oral route at doses of either 1000 mg or 1500 mg.

Efficacy

The efficacy of late sodium current inhibition will be evaluated through several parameters. The primary endpoint is the relative difference in index of microcirculatory resistance (IMR) and/or angioIMR, assessed at baseline following successful coronary revascularization and during staged revascularization of the non-culprit stenosis at either 5±2 days or within 6±2 weeks after percutaneous coronary intervention (pPCI).

Secondary endpoints include:

The prevalence of coronary microvascular dysfunction (CMD) downstream to the culprit vessel, defined as an IMR or angioIMR value greater than 25.
The extent of infarct size, measured in grams and percentage via cardiac magnetic resonance (CMR).
The prevalence of CMD downstream to the non-culprit vessel.
The incidence of peri-procedural CMD after staged pPCI of non-culprit stenoses, identified by a 20% increase in IMR or angioIMR values.
The incidence of periprocedural myocardial infarction (PMI) occurring during the staged procedure, according to the Universal Definition of Myocardial Infarction.
Endothelial function, evaluated using the EndoPAT to measure the Endoscore and reactive hyperemia index (RHI).
The incidence of major adverse cardiovascular events (MACE), comprising death, myocardial infarction, or target-vessel revascularization, at a short-term follow-up of 42±7 days.
Angina symptoms and quality of life, assessed using the SAQ7 and EuroQoL questionnaires.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Age ≥ 18 years and < 80 years on day of signing informed consent
Ability to provide written informed consent in a time window 0 to 1 day after successful pPCI.
ST-Elevation Myocardial Infarction at the time of the index hospitalization.
Successful pPCI (Thrombolysis In Myocardial Infarction [TIMI] flow 3 and residual coronary stenosis <30%).
Presence of at least one remaining angiographically significant (% diameter stenosis > 50%) non-culprit stenosis treatable with PCI.
Evidence of post-menopausal status or negative urinary or serum pregnancy test for child-bearing potential patients (definitions reported in section 10.9)..
Agreement for child-bearing potential patients who are sexually active to use contraception (definitions reported in section 10.10)..

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Exclusion Criteria

Hemodynamically unstable patients
Previous myocardial infarction
Previous coronary artery by-pass graft (CABG)
Female patients with a positive pregnancy test at enrollment or prior to administration of study medication
Female patients who are pregnant or breastfeeding or reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of Ranolazine
Known hypersensitivity to the active principle (Ranolazine) or any of the excipients
Chronic Kidney Disease Stage 4 or 5 (eGFR < 30 mL/min/1.73 m 2)
Moderate to severe liver failure (Child Pugh B – C)
Simultaneous intake of the following classes of drugs: strong CYP3A4 inhibitors (i.e. clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole); HIV protease inhibitors (i.e. saquinavir, indinavir, ritonavir); class Ia antiarrhythmic drugs (i.e. ajmaline, disopyramide, procainamide, quinidine ) and class III antiarrhythmic drugs except amiodarone (i.e. dofetilide, sotalol)
Previous participation in a clinical trial in which an investigational drug was administered within 30 days of screening or within the 5 half-lives of the study drug, whichever is longer.