Levosimendan in Patients With Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery On Cardiopulmonary Bypass
- Conditions
- Coronary Artery Bypass GraftingMitral Valve SurgeryLow Cardiac Output Syndrome
- Interventions
- Drug: LevosimendanDrug: Placebo
- Registration Number
- NCT02025621
- Lead Sponsor
- Tenax Therapeutics, Inc.
- Brief 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).
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 882
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Levosimendan Levosimendan levosimendan 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours Placebo Placebo placebo 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
- Primary Outcome Measures
Name Time Method Number of Dual Efficacy Endpoint Events 30 days The all-cause death at 30 days or use of mechanical assist device (IABP, LVAD or ECMO) following the start of surgery for poor cardiac function despite inotropic support and adequate fluid replacement) through Day 5
Number of Quad Efficacy Endpoint Events 30 days Composite of all-cause death (at 30 days), or perioperative nonfatal MI \[CK-MB \>10xULN or \>100 ng/mL, CK-MB \>5xULN or 50 ng/mL with new Q wave (\>0.04 seconds wide in two contiguous leads) or new left bundle branch block)\] (through Day 5), or need for renal dialysis (through Day 30), or use of mechanical assist device (IABP, LVAD or ECMO) following the start of surgery for poor cardiac function despite inotropic support and adequate fluid replacement) (through Day 5)
- Secondary Outcome Measures
Name Time Method Duration of Intensive Care Unit/Critical or Coronary Care Unit (ICU/CCU) (Days) participants will be followed for during the participant's hospital stay up to 30 days Duration of intensive care unit/critical or coronary care unit (ICU/CCU) length of stay (LOS) in days
Incidence of Low Cardiac Output Syndrome (LCOS) 5 days Use of a mechanical cardiac assist device within 5 days after surgery, two consecutive measurements of low cardiac output (defined as a cardiac output of ≤2.0 liters per minute per square meter of bodysurface area), one measurement of low cardiac output plus the use of two or more inotropes at or beyond 24 hours after surgery, or the use of two or more inotropes at or beyond 24 hours after surgery with the indicated reason being low cardiac output.
Postoperative Use of Secondary Inotrope 24 hours Use of (dobutamine, milrinone, epinephrine, dopamine) associated with index surgical procedure at 24 hours after initiation of surgery
Trial Locations
- Locations (60)
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Duke University Hospital
🇺🇸Raleigh, North Carolina, United States
Iowa Heart Center/ Mercy Medical Center
🇺🇸West Des Moines, Iowa, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Lenox Hill Hospital
🇺🇸New York, New York, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
Maine Medical Center
🇺🇸Portland, Maine, United States
Nebraska Heart Institute
🇺🇸Lincoln, Nebraska, United States
Montreal Heart Institute
🇨🇦Montreal, Quebec, Canada
Mission Hospital
🇺🇸Asheville, North Carolina, United States
McGill University Health Centre-Royal Victoria Hospital
🇨🇦Montreal, Quebec, Canada
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Southlake Regional Health Center
🇨🇦Newmarket, Ontario, Canada
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Royal Jubilee Hospital (Vancouver Island Health Authority)
🇨🇦Victoria, British Columbia, Canada
Institute universitaire de cardiologie et pneumologie de Quebec
🇨🇦Quebec, Canada
St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
St. Peter's Hospital
🇺🇸Albany, New York, United States
University of Alabama at Burlington Hospital
🇺🇸Burlington, Alabama, United States
Huntsville Hospital
🇺🇸Huntsville, Alabama, United States
Hartford Hospital
🇺🇸Hartford, Connecticut, United States
Stanford University School of Medicine
🇺🇸Stanford, California, United States
Shands Hospital at the University of Florida
🇺🇸Gainesville, Florida, United States
Boca Raton Community Hospital
🇺🇸Boca Raton, Florida, United States
Northwestern University Hospital
🇺🇸Evanston, Illinois, United States
Redmond Regional Medical Center
🇺🇸Rome, Georgia, United States
Lutheran Hospital of Indiana
🇺🇸Fort Wayne, Indiana, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Oakwood Hospital and Medical Center
🇺🇸Dearborn, Michigan, United States
Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
Barnes Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
Moses H. Cone Memorial Hospital
🇺🇸Greensboro, North Carolina, United States
Saint Francis Hospital/The Heart Center
🇺🇸Roslyn, New York, United States
Case Medical Center
🇺🇸Cleveland, Ohio, United States
Ohio State University Hospital
🇺🇸Columbus, Ohio, United States
ProMedica Toledo Hospital
🇺🇸Toledo, Ohio, United States
Lehigh Valley Hospital
🇺🇸Allentown, Pennsylvania, United States
Baylor Hospital
🇺🇸Dallas, Texas, United States
The Heart Hospital Baylor Plano
🇺🇸Plano, Texas, United States
Franciscan Health System Res. Center
🇺🇸Tacoma, Washington, United States
University of Virginia Health System
🇺🇸Charlottesville, Virginia, United States
Victoria Heart Institute Foundation
🇨🇦Victoria, British Columbia, Canada
London Health Sciences Center, University Hospital
🇨🇦London, Ontario, Canada
St. Boniface Hospital
🇨🇦Winnepeg, Manitoba, Canada
Hamilton Health Sciences
🇨🇦Hamilton, Ontario, Canada
Aurora Saint Luke's Medical Center
🇺🇸Milwaukee, Wisconsin, United States
Mercy General Hospital
🇺🇸Sacramento, California, United States
University of California San Diego Medical Center
🇺🇸San Diego, California, United States
St. Luke's Hospital
🇺🇸Kansas City, Missouri, United States
Yale-New Haven Hospital
🇺🇸New Haven, Connecticut, United States
Tampa General Hospital
🇺🇸Tampa, Florida, United States
Franciscan St. Francis Health
🇺🇸Indianapolis, Indiana, United States
University of Louisville Hospital
🇺🇸Louisville, Kentucky, United States
St. Joseph's Mercy Hospital
🇺🇸Ann Arbor, Michigan, United States
Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
The Christ's Hospital; Lindner Clinical Trial Center
🇺🇸Cincinnati, Ohio, United States
Oklahoma Heart Hospital
🇺🇸Oklahoma City, Oklahoma, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
St. Thomas Heart
🇺🇸Nashville, Tennessee, United States