Ignite Creation Date:
2024-05-06 @ 8:11 AM
Last Modification Date:
2024-10-26 @ 11:57 AM
Study NCT ID:
NCT02687269
Status:
WITHDRAWN
Last Update Posted:
2021-02-25
First Post:
2016-02-10
Brief Title:
Ranolazine a Potential New Therapeutic Application
Sponsor:
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Organization:
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study Overview
Official Title:
Ranolazine Myocardial Protection in Complete Coronary Artery Bypass Grafting A Randomized-controlled Trial
Status:
WITHDRAWN
Status Verified Date:
2021-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Inability to produce placebo tablets similar to the drug tested
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 IR 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 IR 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 IR 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
Detailed Description:
We aim to perform a prospective single-center investigator-initiated randomized 11 blinded placebo-controlled study The patients undergoing elective and complete CABG revascularization performed by the same surgeon will be randomized in two different groups to receive in the three days before surgery Ranolazine at a dose of 375 mg twice daily or placebo After the enrollement in the research according the inclusion and exclusion criteria the randomization list will be computer-generated The study participants the reserchers responsible for data reporting and analysis and the ecocardiographers will be blinded to the treatment that each patient will receive In a previous phase all data for the recruitment will be considered and registered before surgery basic clinical parameters age gender height weight body surface systolic blood pressure and diastolic blood pressure mean heart rate medical history diabetes mellitus type I or II smoking status chronic obstructive pulmonary desease systemic arterial hypertension dyslipidemia family history of cardiovascular events angina percutaneous coronary interventions PCI acute myocardial infarction AMI previous cardiac surgery chronic peripheral arterial disease cerebral ischemia bleeding and chronic renal failure basic hematologic parameters creatinine glucose hemoglobin hematocrit white blood cell counts and equation platelets number aPTT INR baseline transthoracic echocardiographic TTE parameters left ventricular ejection function LVEF left ventricular volumes left ventricular regional wall motion diastolic function mitral inflow velocities as Early diastolic velocity E late diastolic velocity with atrial contraction A and deceleration time DT early diastolic velocity e and late diastolic velocity with atrial contraction a using tissue Doppler imaging pulmonary artery systolic pressure PASP valvulopathy and aortic desease assestment of risk stratification according to different scores New York Heart Association NYHA classes Canadian Cardiovascular Society CCS Angina grading scale EUROSCORE II American Society og Anesthesiologists ASA physical status classification system preoperative patient therapy In a following phase laboratory hemodynamic and imaging evaluation will be carried out during and subsequent to CABG surgery Through a coronary sinus inserted catheter will be dosed Troponine I TnI immediately before CPB and after the release of aortic cross clamp about 10 minutes after the end of reperfusion TnI will be also dosed at arrival on intensive care unit and 6 12 24 48 h after unclamping of the aorta Blood samples will be collected simultaneously from the radial artery and the coronary sinus before starting CPB and after removal of aortic cross clamp to evaluate lactates extraction oxygen consumption VO2 and oxygen extraction O2ER and C-reactive protein CRP pre and post-CPB Hemodynamic measurements will be obtained by an arterial and a pulmonary artery catheter PAC inserted before surgery and will include arterial pressure systolic diastolic and mean pressure pulmonary artery pressure PAP right atrial pressure RAP pulmonary artery wedge pressure PAWP cardiac output CO and cardiac index CI systemic vascular resistance SVR left ventricular stroke work LVSW left stroke volume variaton LSVV and coronary artery perfusion pressure CPP these measurements will be conducted 30 min after intubation after sternotomy 10 min after protamin after sternosynthesis at arrival in the intensive care unit 6 12 24 36 48 h after CPB Lastly a transesophageal echocardiographic study will be performed by two expert echocardiographers following the protocols of the Society of Cardiovascular Anesthesiologists 21 and American Society of Echocardiography 22 Left ventricle myocardial performance index LVEF left ventricular regional wall motion EA ratio E EE and deceleration time DT of mitral inflow velocity will be measured these measurements will be obteined 30 minute after intubation before sternotomy and ten minute after protamin All collected data will be entered into a database in Excel format
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None