Levosimendan in Patients With Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery On Cardiopulmonary Bypass

Coronary Artery Bypass Grafting Clinical Trial

— LEVO-CTS  

Official title:

A Double-Blind, Randomized, Placebo-Controlled Study of Levosimendan in Patients With Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02025621
• Other study ID #: TNX-LVO-01
• Status: Completed
• Phase: Phase 3
• Start date: July 2014
• Est. completion date: November 2016

Study information

• Verified date: May 2018
• Source: Tenax Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 882
• Est. completion date: November 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cardiac Output, Low
• Coronary Artery Bypass Grafting
• Low Cardiac Output Syndrome
• Mitral Valve Surgery
• Ventricular Dysfunction, Left

Intervention

Drug:
• Levosimendan

• Placebo
matching placebo

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Tenax Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Occurrence of All-cause Mortality From Randomization Through Day 90		90 days
Other	Rehospitalization for Any Cause Through Day 30		30 days
Primary	Number of Dual Efficacy Endpoint Events	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
Primary	Number of Quad Efficacy Endpoint Events	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	Duration of Intensive Care Unit/Critical or Coronary Care Unit (ICU/CCU) (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
Secondary	Incidence of Low Cardiac Output Syndrome (LCOS)	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
Secondary	Postoperative Use of Secondary Inotrope	Use of (dobutamine, milrinone, epinephrine, dopamine) associated with index surgical procedure at 24 hours after initiation of surgery	24 hours