Inhibition of Late Sodium Current (INa) to Prevent Coronary MICROvascular Dysfunction in Patients Presenting With ST-Elevation Myocardial Infarction and Multivessel Disease: INaMICRON Study

Summary

This is a Phase IIb, multicentric, prospective, randomized (1:1 ratio), open label, and no profit study, with the aim of evaluating the efficacy of late INa current inhibition to improve coronary microcirculation in patients presenting with acute myocardial infarction and multivessel disease. All consecutive patients presenting with acute MI undergoing primary PCI (pPCI) on a major coronary artery, and with at least one remaining angiographically significant (% diameter stenosis \> 50%) non-culprit stenosis will be enrolled. The primary objective of the study is to evaluate the potential effect of Ranolazine in preserving coronary microcirculation subtended to the culprit vessel as compared with control group. Coronary microcirculation will be assessed both at the time of the culprit lesion revascularization and within 6+/-2 weeks by measuring the Index of Microcirculatory Resistance (IMR) either invasively or derived by the angiography (angioIMR). In addition, the following secondary endpoints will be assessed: 1. The prevalence of residual CMD downstream to the culprit vessel in all patients (CMDculprit). CMDculprit will be defined as the finding of an IMR/angioIMR value \> 25, assessed after successful pPCI. 2\. The prevalence of CMD downstream to the non-culprit vessel in the two group of patients (CMDnon-culprit). CMDnon-culprit will be defined as the finding of an IMRnon-culprit or an angioIMRnon-culprit value \> 25. IMRnon-culprit or angioIMRnon-culprit will be assessed at the time of staged PCI of the non-culprit stenosis. 3\. The incidence of peri-procedural CMD after staged PCI of the non-culprit stenoses, defined as a 20% increase of IMR values assessed before and after elective PCI of the non-culprit vessel (CMDprocedural). 4\. The difference between the two groups of patients, in terms of incidence of periprocedural Myocardial Infarction (PMI), eventually occurring during the staged procedure. 5\. The effects of INa current inhibition on endothelial function assessed at follow up as compared with control group. 6\. The extent of the Infarct Size, as assessed by the CMR, as compared with control group. 7\. The incidence of MACE, defined as composite of death, myocardial infarction, periprocedural MI, or any unplanned percutaneous coronary revascularization at short (42+/-7 days) term follow-up. 8\. Angina symptoms and quality of life

Eligibility

Inclusion Criteria

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

Exclusion Criteria:

1. Hemodynamically unstable patients
2. Previous myocardial infarction
3. Previous coronary artery by-pass graft (CABG)
4. Female patients with a positive pregnancy test at enrollment or prior to administration of study medication.
5. 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
6. Known hypersensitivity to the active principle (Ranolazine) or any of the excipients
7. Chronic Kidney Disease Stage 4 or 5 (eGFR \< 30 mL/min/1.73 m 2)
8. Moderate to severe liver failure (Child Pugh B - C)
9. 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)
10. 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.

Conditions2

Interventions1

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