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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universita' Degli Studi Di Napoli Federico II

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

3 Mar 2026 → ongoing

Decision date (initial)

2025-10-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

PRIN PNRR financing fund.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

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.

Secondary objectives 8

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.

Conditions and MedDRA coding

Acute myocardial infarction in patients presenting with STEMI and multivessel disease.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

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 10

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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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).

Secondary endpoints 8

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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universita' Degli Studi Di Napoli Federico II

Sponsor organisation

Universita' Degli Studi Di Napoli Federico II

Address

Via Sergio Pansini 5

City

Naples

Postcode

80131

Country

Italy

Scientific contact point

Organisation

Universita' Degli Studi Di Napoli Federico II

Contact name

Luigi Di Serafino

Public contact point

Organisation

Universita' Degli Studi Di Napoli Federico II

Contact name

Luigi Di Serafino

Third parties 2

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications