Levosimendan in Patients With Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery On Cardiopulmonary Bypass

A Double-Blind, Randomized, Placebo-Controlled Study of Levosimendan in Patients With Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass

A study to evaluate levosimendan compared with placebo in reducing the composite event rate of all-cause death, perioperative MI, need for new dialysis, or use of mechanical assist (IABP, LVAD or ECMO) in subjects with reduced ejection fraction undergoing cardiac surgery on cardiopulmonary bypass (CPB).

This study is being done to evaluate the efficacy of levosimendan compared with placebo in reducing the co-primary endpoints of 30-day composite of all-cause death or use of mechanical assist device (IABP, LVAD or ECMO) or the composite event rate of all-cause death, perioperative MI, need for dialysis, or use of mechanical assist (IABP, LVAD or ECMO) in subjects with reduced ejection fraction undergoing cardiac surgery on CPB.

Inclusion Criteria:

• Documented LVEF ≤35% measured by ventriculogram, echocardiogram (ECHO), nuclear scan, or MRI within 60 days before surgery.
• Scheduled or urgent 1) CABG surgery, 2)CABG with aortic valve surgery, 3) CABG with mitral valve surgery, or 4) mitral valve surgery with or without other valves
• Surgery will employ CPB pump
• Signed (by the subjects or their legally acceptable representatives) informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study

Exclusion Criteria:

• Restrictive or obstructive cardiomyopathy, constrictive pericarditis, restrictive pericarditis, pericardial tamponade, or other conditions in which cardiac output is dependent on venous return.
• Evidence of systemic bacterial, systemic fungal, or viral infection within 72 hours before surgery.
• Dialysis at randomization (either hemodialysis, peritoneal dialysis, continuous venovenous hemofiltration, or ultrafiltration).
• Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2.
• Weight ≥ 170 kg.
• Patients whose SBP cannot be managed to ensure SBP > 90 mmHg at initiation of study drug.
• Heart rate ≥ 120 bpm, persistent for at least 10 minutes screening and unresponsive to treatment.
• Hemoglobin < 80 g/L.
• Serum potassium < 3.5 mmol/L and > 5.5 mmol/L at baseline.
• A history of Torsades de Pointes.
• Mechanical assist device (IABP, LVAD, ECMO) in the patient at the start of surgery or pre-planned to be inserted during surgery before coming off CPB.
• Patients with aortal femoral occlusive disease that would prohibit use of IABP unless VAD or ECMO not available.
• Liver dysfunction Child Pugh Class B or C
• Patients having severely compromised immune function
• Pregnant, suspected to be pregnant, or breast-feeding.
• Received an experimental drug or used an experimental medical device in previous 30 days.
• Known allergic reaction or sensitivity to Levosimendan or excipients.
• Received commercial Levosimendan within 30 days before the planned start of study drug.
• Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator.