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Ranolazine a Potential New Therapeutic Application

NCT02687269 · Status: WITHDRAWN · Phase: PHASE4 · Type: INTERVENTIONAL

Last updated 2021-02-25

No results posted yet for this study

Summary

Despite surgical and medical innovation have reduced mortality rates in cardiac surgery, the disease severity and operative procedural complexity have increased and morbidity rate is still high. Ischemia-reperfusion (I/R) injury, redefined in cardiac surgery "post-cardioplegic injury" (2) as a whole of ischemia-reperfusion, cardiopulmonary bypass and surgical trauma, has been recognized as a significant contributor to mortality and morbidity. I/R injury is classified as reversible or irreversible. Reversible injury includes arrhythmias, edema, vascular dysfunction and contractile stunning expressed as low output syndrome without cell death and without apparent signs of infarction or other serum injury markers. Irreversible reperfusion injury includes apoptosis and necrosis. I/R injury is a complex process associated with increase of radical, oxidant and cytokines production, complement and neutrophil activation and endothelial activation leading to microvascular dysfunction and deterioration of coronary flow reserve. In the hypoxic heart increase anaerobic lactate production, K+ efflux and membrane depolarization. The intracellular Na+ concentration rises as a consequence of slow Na+ channels inactivation and the induction of voltage-gated Na+ channel late current component (late INA). Intracellular Na++ accumulation enhanced activity of reversed-mode Na+-Ca++ exchanger causing intracellular Ca++ overload and ventricular dysfunction. Therefore inhibition of late INA has been shown to be cardioprotective. Ranolazine, an FDA-approval antianginal and anti-ischemic agent, high selective blocker of late INA, inhibits the late sodium current in myocardial ischemia, decreases Na+ and Ca2+ overload and improves left ventricular function in experimental animal models. For this reason it was also adjuncted to cardioplegia improving diastolic function in isolate Langerdoff-perfused rat hearts. The authors test the hypothesis that ranolazine improve myocardical protection in patients undergoing coronary artery surgery with cardiopulmonary by-pass (CPB).

Conditions

  • Myocardial Stunning

Interventions

DRUG

Ranolazine

Patients in this arm receive Ranolazine at a dose of 375 mg twice daily in the three days before surgery

DRUG

Placebo

Patients receive Placebo twice daily in the three days before surgery

Sponsors & Collaborators

  • Fondazione Policlinico Universitario Agostino Gemelli IRCCS

    lead OTHER

Principal Investigators

  • Gabriella Arlotta, MD · Department cardiovascular diseases A. Gemelli Polyclinic , University Sacred Heart in Rome

Study Design

Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Model
PARALLEL

Eligibility

Min Age
18 Years
Max Age
80 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2019-04-10
Primary Completion
2020-09-30
Completion
2020-10-31

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02687269 on ClinicalTrials.gov