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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified June 2014 by Oxygen Biotherapeutics, Inc.
Sponsor:
Information provided by (Responsible Party):
Oxygen Biotherapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT02025621
First received: December 18, 2013
Last updated: June 4, 2014
Last verified: June 2014
  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 or LVAD) 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 Oxygen Biotherapeutics, 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 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 (through Day 5) [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)], or need for renal dialysis (through Day 30), or use of mechanical assist device (IABP or LVAD 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, norepinephrine) [ 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, norepinephrine), with the fluid balance and maximal inotropic dose at the investigator's discretion)

  • Postoperative use of secondary inotrope (dobutamine, milrinone, epinephrine, and norepinephrine) 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: January 2016
Estimated Primary Completion Date: January 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 or LVAD) or the composite event rate of all-cause death, perioperative MI, need for dialysis, or use of mechanical assist (IABP or LVAD) in subjects with reduced ejection fraction undergoing cardiac surgery on CPB.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documented LVEF ≤25% (CABG patients) or LVEF ≤35% (CABG with mitral valve or isolated mitral valve surgery patients) by ventriculogram, echocardiogram (ECHO), or nuclear scan, within 60 days before surgery.
  • Scheduled to undergo 1) CABG surgery with or without mitral valve replacement, or 2) isolated mitral valve repair; all patients on CPB.
  • 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.
  • Pulmonary disease (severe chronic obstructive pulmonary disease [COPD], asthma, or other condition) that, in the opinion of the investigator, represents an independent clinical risk to the cardiac surgery and recovery of the patient.
  • Evidence of systemic bacterial, systemic fungal, or viral infection within 72 hours before surgery.
  • Chronic dialysis at baseline or within 30 days of CABG/mitral valve surgery (either hemodialysis, peritoneal dialysis, continuous venovenous hemodialysis).
  • Estimated glomerular filtration rate (eGFR) < 30 mL/kg/min or evidence of worsening renal function before CABG/mitral valve surgery.
  • 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.
  • Hemoglobin < 80 g/L within 4 hours before baseline.
  • Serum potassium < 3.5 mmol/L and > 5.5 mmol/L at baseline.
  • A history of Torsades de Pointes.
  • Mechanical assist device (IABP, LVAD) in previous 30 days or pre-planned use of IABP or LVAD during or following CABG/mitral valve surgery.
  • Patients with aortal femoral inclusive disease that would prohibit use of IABP.
  • Planned aortic valve repair or replacement.
  • Liver dysfunction Child Pugh Class B or C (see Attachment 3)
  • 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@oxybiomed.com

Locations
United States, North Carolina
Duke University Hospital Not yet recruiting
Raleigh, North Carolina, United States, 27710
Contact: Rajendra Mehta, MD       raj.mehta@duke.edu   
Sponsors and Collaborators
Oxygen Biotherapeutics, Inc.
Investigators
Principal Investigator: Rajendra Mehta, MD Duke Clinical Research Institute
Study Chair: John Alexander, MD Duke Clinical Research Institute
  More Information

No publications provided

Responsible Party: Oxygen Biotherapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02025621     History of Changes
Other Study ID Numbers: PYX-LVO-01
Study First Received: December 18, 2013
Last Updated: June 4, 2014
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Cardiac Output, Low
Ventricular Dysfunction, Left
Heart Diseases
Cardiovascular Diseases
Signs and Symptoms
Ventricular Dysfunction
Simendan
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
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 21, 2014