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

May 22, 2018 updated by: Tenax Therapeutics, Inc.

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

882

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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 Names:
  • 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
30 days
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)
30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
participants will be followed for during the participant's hospital stay up to 30 days
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.
5 days
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
24 hours

Other Outcome Measures

Outcome Measure
Time Frame
Occurrence of All-cause Mortality From Randomization Through Day 90
Time Frame: 90 days
90 days
Rehospitalization for Any Cause Through Day 30
Time Frame: 30 days
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tenax Therapeutics, Inc.

Investigators

  • Principal Investigator: Rajendra Mehta, MD, Duke Clinical Research Institute
  • Study Chair: John Alexander, MD, Duke Clinical Research Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2014

Primary Completion (Actual)

November 1, 2016

Study Completion (Actual)

November 1, 2016

Study Registration Dates

First Submitted

December 18, 2013

First Submitted That Met QC Criteria

December 30, 2013

First Posted (Estimate)

January 1, 2014

Study Record Updates

Last Update Posted (Actual)

June 21, 2018

Last Update Submitted That Met QC Criteria

May 22, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TNX-LVO-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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