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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by Tenax Therapeutics, Inc.
Sponsor:
Information provided by (Responsible Party):
Tenax Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT02025621
First received: December 18, 2013
Last updated: August 11, 2016
Last verified: August 2016
  Purpose
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 Intervention Phase
Coronary Artery Bypass Grafting
Mitral Valve Surgery
Low Cardiac Output Syndrome
Drug: Levosimendan
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Tenax Therapeutics, Inc.:

Primary Outcome Measures:
  • Co-primary Efficacy Endpoint [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    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

  • Co-primary Efficacy Endpoint [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    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:
  • Duration of intensive care unit/critical or coronary care unit (ICU/CCU) [ Time Frame: participants will be followed for during the participant's hospital stay up to 30 days ] [ Designated as safety issue: No ]
    Duration of intensive care unit/critical or coronary care unit (ICU/CCU) length of stay (LOS)

  • Incidence of LCOS defined as cardiac index ≤ 2.0 L/min/m2 for ≥30 minutes despite optimal fluid balance and maximal inotropic support (dobutamine, milrinone, epinephrine, dopamine) [ Time Frame: 5 days ] [ Designated as safety issue: No ]
    Incidence of LCOS defined as cardiac index ≤ 2.0 L/min/m2 for ≥30 minutes despite optimal fluid balance and maximal inotropic support (dobutamine, milrinone, epinephrine, dopamine), with the fluid balance and maximal inotropic dose at the investigator's discretion)

  • Postoperative use of secondary inotrope (dobutamine, milrinone, epinephrine, dopamine) associated with index surgical procedure [ Time Frame: 5 days ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Occurrence of all-cause mortality from randomization through Day 90 [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
  • Postoperative incidence of atrial fibrillation [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]
  • Rehospitalization for any cause through Day 30 [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 760
Study Start Date: July 2014
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
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 ultrafilitration).
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02025621

Contacts
Contact: Douglas Hay, PhD 919-855-2110 d.hay@tenaxthera.com

  Show 63 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
  More Information

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 
Study First Received: December 18, 2013
Last Updated: August 11, 2016
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Cardiac Output, Low
Ventricular Dysfunction, Left
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

ClinicalTrials.gov processed this record on August 25, 2016