Ranolazine to prevent coronary microvascular damage after STEMI in people with multivessel coronary disease

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

This trial will try ranolazine in adults who have a STEMI and remaining significant blockages to see if it protects the small blood vessels in the heart after emergency angioplasty.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Federico II University (Academic / other)
• Locations: 3 sites (Catanzaro, Italy and 2 other locations)
• Trial ID: NCT07380919 on ClinicalTrials.gov

What this trial studies

This is a Phase IIb/III multicenter, randomized (1:1), open-label, no-profit trial comparing ranolazine versus usual care in patients presenting with STEMI and at least one angiographically significant non-culprit stenosis. Consecutive adults undergoing successful primary PCI with a residual non-culprit lesion >50% will be enrolled and randomized to receive ranolazine or control. The primary endpoint is the relative change in Index of Microcirculatory Resistance (IMR) or angiography-derived angioIMR measured at baseline (after culprit revascularization) and again at the time of staged non-culprit PCI (either 5±2 days or within 6±2 weeks). Secondary objectives include rates and extent of coronary microvascular dysfunction and measures of recurrent ischemia.

Who should consider this trial

Good fit: Adults aged 18 to <80 who present with STEMI, undergo successful primary PCI (TIMI 3, residual stenosis <30%), have at least one remaining angiographically significant (>50%) non-culprit lesion treatable with PCI, and can provide informed consent are ideal candidates.

Not a fit: Patients who are hemodynamically unstable, have a history of prior myocardial infarction or CABG, are pregnant, or do not have multivessel disease are unlikely to be eligible or to derive benefit from this protocol.

Why it matters

Potential benefit: If successful, ranolazine could help preserve coronary microvascular function after STEMI, potentially reducing recurrent ischemia and improving recovery of the affected heart muscle.

How similar studies have performed: Ranolazine has been tested previously in acute coronary syndromes without reducing major adverse cardiovascular events but did lower recurrent ischemia, while using IMR/angioIMR as the primary microvascular endpoint is a more novel application.

Eligibility criteria

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.

Where this trial is running

Catanzaro, Italy and 2 other locations

• Department of Medical and Surgical Sciences and "Renato Dulbecco" University Hospital, "Magna Graecia" University — Catanzaro, Italy, Italy (Recruiting)
• Department of Cardiology, Santa Maria Goretti Hospital, Latina, Italy — Latina, Italy, Italy (Not_yet_recruiting)
• Federico II University Hospital - Division of Cardiology — Naples, Italy (Recruiting)

Study contacts

• Study coordinator: Luigi Di Serafino, Professor

Conditions STEMI; Coronary Microvascular Dysfunction; Ranolazine; Multivessel Coronary Artery Disease