Levosimendan in Patients With Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery On Cardiopulmonary Bypass
Condition: Coronary Artery Bypass Grafting; Mitral Valve Surgery; Low Cardiac Output Syndrome
MeSH terms: Ventricular Dysfunction, Left; Cardiac Output, Low
Intervention: Levosimendan; Placebo
Intervention description: matching placebo
Intervention MeSH terms: Simendan
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 882.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: coronary artery bypass grafting; CABG; mitral valve; LCOS; low cardiac output syndrome; levosimendan

Summary:

      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).
    

Eligibility criteria:

        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.