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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


  Show 60 Study Locations
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