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

March 9, 2026 updated by: Luigi Di Serafino, Federico II University

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 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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Ranolazine has already been studied in the setting of the acute coronary syndromes, without any significant advantage in terms of MACE occurrence as compared with control group. However, it was not associated with any significant adverse event, thereby the use of ranolazine is not forbidden in ACS patients, especially in the setting of patients with MVD. Of note, the individual component of recurrent ischemia was significantly reduced by ranolazine, as compared with control group and ranolazine reduced recurrent ischemic events, regardless of whether patients did or did not receive PCI within 30 days of a non-ST-segment ACS.

The aim of the present multicenter, randomized, controlled and open-label study is to evaluate the efficacy of late INa current inhibition to preserve coronary microcirculation after the acute myocardial infarction in patients presenting with STEMI and multivessel disease. Thereby, primary endpoint will be the relative difference in terms of IMR and/or angioIMR will be evaluated. IMR and/or angioIMR will be assessed both at the baseline (after successful coronary revascularization) and at the time of staged revascularization of the non-culprit stenosis (either at 5+/-2 days or within 6+/-2 weeks after pPCI).

In addition, as secondary objectives, It will be assessed whether the late INa current inhibition, as compared with the control group, might be effective at:

  1. Reducing the prevalence of CMD after successful pPCI
  2. Reducing the extension of the infarct size, as assessed at the cardiac magnetic resonance
  3. Reducing the prevalence of CMD downstream to the non-culprit vessel before staged PCI
  4. Reducing the incidence of CMD downstream to the non-culprit vessel after staged PCI
  5. Reducing the incidence of periprocedural MI eventually occurring after staged procedures
  6. Reducing the incidence of endothelial dysfunction
  7. Reducing the early incidence of major cardiovascular events (MACE)
  8. Improving residual angina symptoms and quality of life

Thereby, the following secondary endpoints will be evaluated:

  1. The prevalence of residual CMD downstream to the culprit vessel in the two group of patients. Residual CMD will be defined as the finding of an IMRculprit or angioIMRculprit value > 25
  2. The extent of the Infarct Size, as assessed by the CMR, in terms of grams (g) and percentage as compared with control group.
  3. 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 angioIMRnon-culprit value > 25
  4. The incidence of peri-procedural CMD after staged PCI of the non-culprit stenoses, defined as a 20% increase of IMRnon-culprit or angioIMRnon-culprit values assessed before and after elective PCI of the non-culprit vessel.
  5. The difference between the two groups of patients, in terms of incidence of periprocedural Myocardial Infarction (PMI), eventually occurring during the staged procedure. PMI require to satisfy all the criteria of the fourth Universal Definition of Myocardial Infarction
  6. The effects of INa current inhibition on endothelial function will be assessed at follow up as compared with control group. Endothelial function will be evaluated with the EndoPAT, measuring both the Endoscore and RHI
  7. The incidence of MACE, defined as composite of death, myocardial infarction, or target-vessel revascularization at short (42+/-7 days) term follow-up.
  8. Angina symptoms and quality of life will be assessed with SAQ7 and EuroQoL questionnaires and results compared between the two groups. Study Design This will be a prospective, multicenter, randomized (1:1 ratio), open-label, trial to evaluate the relative difference in terms of IMR and/or angioIMR measured both at baseline (after successful pPCI) and at follow-up (during staged PCI procedure).

Patients enrolled in the experimental group will receive ranolazine by oral administration, on top of regular therapy, starting with a dosage of 500mg bid and increased at 750mg bid starting from 7 days after pPCI up to 6 +/-2 weeks. Conversely, patients enrolled in the Control group will be managed, as per standard practice, with regular therapy only.

All comer patients undergoing successful pPCI for ST-segment elevation myocardial infarction (STEMI) will be screened for eligibility for study participation within six hours. STEMI will be defined by symptom onset within 24 hours and ST-segment elevation of ≥ 1 mm in 2 or more contiguous leads, true posterior MI, or new left bundle branch block. Patients who fulfil all inclusion criteria and do not meet any of the exclusion criteria will be eligible for trial inclusion soon after successful pPCI. Patients will be informed on the nature of the trial and of any potential harm or risk that the study may cause and will be assured of confidentiality. Patients will receive a copy of the signed and dated written informed consent form.

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
      • Napoli, Italy
        • Recruiting
        • Federico II University Hospital - Division of Cardiology
        • Contact:
        • Contact:
    • Italy
      • Catanzaro, Italy, Italy, 88100
        • Recruiting
        • Department of Medical and Surgical Sciences and "Renato Dulbecco" University Hospital, "Magna Graecia" University
        • Contact:
          • Salvatore De Rosa, Full Professor
          • Phone Number: 0961/3697123
          • Email: saderosa@unicz.it
      • Latina, Italy, Italy
        • Not yet recruiting
        • Department of Cardiology, Santa Maria Goretti Hospital, Latina, Italy
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental Group
Patients enrolled in the experimental group will receive ranolazine by oral administration, on top of regular therapy, starting with a dosage of 500mg bid and increased at 750mg bid starting from 7 days after pPCI up to 6 +/-2 weeks.
Drug: Ranolazine
Patients enrolled in the experimental group will receive ranolazine by oral administration, on top of regular therapy, starting with a dosage of 500mg bid and increased at 750mg bid starting from 7 days after pPCI up to 6 +/-2 weeks.
No Intervention: Control Group
Patients enrolled in the Control group will be managed, as per standard practice, with regular therapy only.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Preservation of the coronary microcirculation
Time Frame: Up to 8 weeks
he relative difference in terms of IMR and/or angioIMR will be evaluated. IMR and/or angioIMR will be assessed both at the baseline (after successful coronary revascularization) and at the time of staged revascularization of the non-culprit stenosis (either at 5+/-2 days or within 6+/-2 weeks after pPCI).
Up to 8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in terms of CMD prevalence between the two groups
Time Frame: Up to 8 weeks
The prevalence of residual CMD downstream to the culprit vessel in the two group of patients. Residual CMD will be defined as the finding of an IMRculprit or angioIMRculprit value > 25
Up to 8 weeks
Infarct Size Extension
Time Frame: Up to 8 weeks
The extent of the Infarct Size, as assessed by the CMR, in terms of grams (g) and percentage as compared with control group
Up to 8 weeks
CMD prevalence downstream to the non-culprit vessel before staged PCI
Time Frame: Up to 8 weeks
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 angioIMRnon-culprit value > 25
Up to 8 weeks
CMD prevalence after staged PCI
Time Frame: Up to 8 weeks
The incidence of peri-procedural CMD after staged PCI of the non-culprit stenoses, defined as a 20% increase of IMRnon-culprit or angioIMRnon-culprit values assessed before and after elective PCI of the non-culprit vessel.
Up to 8 weeks
Incidence of periprocedural MI eventually occurring after staged procedures
Time Frame: Up to 8 weeks
The difference between the two groups of patients, in terms of incidence of periprocedural Myocardial Infarction (PMI), eventually occurring during the staged procedure. PMI require to satisfy all the criteria of the fourth Universal Definition of Myocardial Infarction
Up to 8 weeks
Incidence of MACE
Time Frame: Up to 8 weeks
The incidence of MACE, defined as composite of death, myocardial infarction, or target-vessel revascularization at short (42+/-7 days) term follow-up.
Up to 8 weeks
Residual angina symptoms
Time Frame: Up to 8 weeks
Angina symptoms will be assessed with The SAQ-7 (Seattle Angina Questionnaire-7) summary score which is a 0-100 validated measure of coronary artery disease (CAD) patient health status, averaging Physical Limitation, Angina Frequency, and Quality of Life domains. Higher scores (0-100) indicate better health status, less frequent angina, and improved quality of life and results compared between the two groups.
Up to 8 weeks
Patients' Quality of Life
Time Frame: Up to 8 weeks
Quality of life will be assessed with the EQ5D5L including a vertical visual analogue scale (EQ VAS) that allows patients to self-rate their current, overall health-related quality of life from 0 ("worst imaginable health") to 100 ("best imaginable health").
Up to 8 weeks
Incidence of endothelial dysfunction
Time Frame: Up to 8 weeks
The effects of INa current inhibition on endothelial function will be assessed at follow up as compared with control group. Endothelial function will be evaluated with the EndoPAT, measuring both the Endoscore and RHI
Up to 8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Federico II University

Collaborators

Università Magna Grecia, Catanzaro
Santa Maria Goretti Hospital, Latina

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

February 1, 2026

Primary Completion (Estimated)

June 1, 2026

Study Completion (Estimated)

June 1, 2026

Study Registration Dates

First Submitted

January 15, 2026

First Submitted That Met QC Criteria

January 23, 2026

First Posted (Actual)

February 2, 2026

Study Record Updates

Last Update Posted (Actual)

March 11, 2026

Last Update Submitted That Met QC Criteria

March 9, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2025-520801-12-00

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

It will be shared upon request

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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