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Levosimendan in Patients With Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery On Cardiopulmonary Bypass (LEVO-CTS)

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ClinicalTrials.gov Identifier: NCT02025621
Recruitment Status : Completed
First Posted : January 1, 2014
Results First Posted : May 22, 2018
Last Update Posted : June 21, 2018
Sponsor:
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
Coronary Artery Bypass Grafting Mitral Valve Surgery Low Cardiac Output Syndrome Drug: Levosimendan Drug: Placebo Phase 3

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 882 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Double-Blind, Randomized, Placebo-Controlled Study of Levosimendan in Patients With Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass
Study Start Date : July 2014
Actual Primary Completion Date : November 2016
Actual Study Completion Date : November 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Surgery

Arm Intervention/treatment
Experimental: Levosimendan
levosimendan 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Drug: Levosimendan
Other Name: Simdax

Placebo Comparator: Placebo
placebo 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Drug: Placebo
matching placebo




Primary Outcome Measures :
  1. Number of Dual Efficacy Endpoint Events [ Time Frame: 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

  2. Number of Quad Efficacy Endpoint Events [ Time Frame: 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 :
  1. Duration of Intensive Care Unit/Critical or Coronary Care Unit (ICU/CCU) (Days) [ Time Frame: 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

  2. Incidence of Low Cardiac Output Syndrome (LCOS) [ Time Frame: 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.

  3. Postoperative Use of Secondary Inotrope [ Time Frame: 24 hours ]
    Use of (dobutamine, milrinone, epinephrine, dopamine) associated with index surgical procedure at 24 hours after initiation of surgery


Other Outcome Measures:
  1. Occurrence of All-cause Mortality From Randomization Through Day 90 [ Time Frame: 90 days ]
  2. Rehospitalization for Any Cause Through Day 30 [ Time Frame: 30 days ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02025621


  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Burlington Hospital
Burlington, Alabama, United States
Huntsville Hospital
Huntsville, Alabama, United States
United States, California
Mercy General Hospital
Sacramento, California, United States
University of California San Diego Medical Center
San Diego, California, United States
Stanford University School of Medicine
Stanford, California, United States
United States, Connecticut
Hartford Hospital
Hartford, Connecticut, United States
Yale-New Haven Hospital
New Haven, Connecticut, United States
United States, Florida
Boca Raton Community Hospital
Boca Raton, Florida, United States
Shands Hospital at the University of Florida
Gainesville, Florida, United States
Tampa General Hospital
Tampa, Florida, United States
United States, Georgia
Redmond Regional Medical Center
Rome, Georgia, United States
United States, Illinois
Northwestern University Hospital
Evanston, Illinois, United States
United States, Indiana
Lutheran Hospital of Indiana
Fort Wayne, Indiana, United States
Franciscan St. Francis Health
Indianapolis, Indiana, United States
United States, Iowa
Iowa Heart Center/ Mercy Medical Center
West Des Moines, Iowa, United States
United States, Kentucky
University of Louisville Hospital
Louisville, Kentucky, United States
United States, Maine
Maine Medical Center
Portland, Maine, United States
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States
Tufts Medical Center
Boston, Massachusetts, United States
United States, Michigan
St. Joseph's Mercy Hospital
Ann Arbor, Michigan, United States
Oakwood Hospital and Medical Center
Dearborn, Michigan, United States
Spectrum Health
Grand Rapids, Michigan, United States
United States, Missouri
St. Luke's Hospital
Kansas City, Missouri, United States
Barnes Jewish Hospital
Saint Louis, Missouri, United States
United States, Nebraska
Nebraska Heart Institute
Lincoln, Nebraska, United States
Nebraska Medical Center
Omaha, Nebraska, United States
United States, New Jersey
Morristown Medical Center
Morristown, New Jersey, United States
United States, New York
St. Peter's Hospital
Albany, New York, 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
Saint Francis Hospital/The Heart Center
Roslyn, New York, United States
United States, North Carolina
Mission Hospital
Asheville, North Carolina, United States
Moses H. Cone Memorial Hospital
Greensboro, North Carolina, United States
Duke University Hospital
Raleigh, North Carolina, United States
United States, Ohio
The Christ's Hospital; Lindner Clinical Trial Center
Cincinnati, Ohio, United States
Case Medical Center
Cleveland, Ohio, United States
Cleveland Clinic
Cleveland, Ohio, United States
Ohio State University Hospital
Columbus, Ohio, United States
ProMedica Toledo Hospital
Toledo, Ohio, United States
United States, Oklahoma
Oklahoma Heart Hospital
Oklahoma City, Oklahoma, United States
United States, Pennsylvania
Lehigh Valley Hospital
Allentown, Pennsylvania, United States
United States, Tennessee
St. Thomas Heart
Nashville, Tennessee, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
United States, Texas
Baylor Hospital
Dallas, Texas, United States
The Heart Hospital Baylor Plano
Plano, Texas, United States
United States, Virginia
University of Virginia Health System
Charlottesville, Virginia, United States
United States, Washington
Franciscan Health System Res. Center
Tacoma, Washington, United States
United States, Wisconsin
Aurora Saint Luke's Medical Center
Milwaukee, Wisconsin, United States
Canada, Alberta
University of Alberta Hospital
Edmonton, Alberta, Canada
Canada, British Columbia
Royal Jubilee Hospital (Vancouver Island Health Authority)
Victoria, British Columbia, Canada
Victoria Heart Institute Foundation
Victoria, British Columbia, Canada
Canada, Manitoba
St. Boniface Hospital
Winnepeg, Manitoba, Canada
Canada, Ontario
Hamilton Health Sciences
Hamilton, Ontario, Canada
London Health Sciences Center, University Hospital
London, Ontario, Canada
Southlake Regional Health Center
Newmarket, Ontario, Canada
St. Michael's Hospital
Toronto, Ontario, Canada
Canada, Quebec
McGill University Health Centre-Royal Victoria Hospital
Montreal, Quebec, Canada
Montreal Heart Institute
Montreal, Quebec, Canada
Canada
Institute universitaire de cardiologie et pneumologie de Quebec
Quebec, Canada
Sponsors and Collaborators
Tenax Therapeutics, Inc.
Investigators
Principal Investigator: Rajendra Mehta, MD Duke Clinical Research Institute
Study Chair: John Alexander, MD Duke Clinical Research Institute

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Tenax Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02025621     History of Changes
Other Study ID Numbers: TNX-LVO-01
First Posted: January 1, 2014    Key Record Dates
Results First Posted: May 22, 2018
Last Update Posted: June 21, 2018
Last Verified: May 2018

Keywords provided by Tenax Therapeutics, Inc.:
coronary artery bypass grafting
CABG
mitral valve
LCOS
low cardiac output syndrome
levosimendan

Additional relevant MeSH terms:
Ventricular Dysfunction, Left
Cardiac Output, Low
Ventricular Dysfunction
Heart Diseases
Cardiovascular Diseases
Signs and Symptoms
Simendan
Anti-Arrhythmia Agents
Cardiotonic Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Protective Agents
Physiological Effects of Drugs