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

NCT ID: NCT02025621

Last Updated: 2018-06-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 882 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2016-11-30

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).

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.

Conditions

Coronary Artery Bypass Grafting; Mitral Valve Surgery; Low Cardiac Output Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Levosimendan

levosimendan 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours

Group Type: EXPERIMENTAL

Levosimendan

Intervention Type: DRUG

Placebo

placebo 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

matching placebo

Interventions

Levosimendan

Intervention Type: DRUG

Placebo

matching placebo

Intervention Type: DRUG

Other Intervention Names

Simdax

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tenax Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rajendra Mehta, MD

Role: PRINCIPAL_INVESTIGATOR

Duke Clinical Research Institute

John Alexander, MD

Role: STUDY_CHAIR

Duke Clinical Research Institute

Locations

University of Alabama at Burlington Hospital

Burlington, Alabama, United States

Huntsville Hospital

Huntsville, Alabama, United States

Mercy General Hospital

Sacramento, California, United States

University of California San Diego Medical Center

San Diego, California, United States

Stanford University School of Medicine

Stanford, California, United States

Hartford Hospital

Hartford, Connecticut, United States

Yale-New Haven Hospital

New Haven, Connecticut, United States

Boca Raton Community Hospital

Boca Raton, Florida, United States

Shands Hospital at the University of Florida

Gainesville, Florida, United States

Tampa General Hospital

Tampa, Florida, United States

Redmond Regional Medical Center

Rome, Georgia, United States

Northwestern University Hospital

Evanston, Illinois, United States

Lutheran Hospital of Indiana

Fort Wayne, Indiana, United States

Franciscan St. Francis Health

Indianapolis, Indiana, United States

Iowa Heart Center/ Mercy Medical Center

West Des Moines, Iowa, United States

University of Louisville Hospital

Louisville, Kentucky, United States

Maine Medical Center

Portland, Maine, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Tufts Medical Center

Boston, Massachusetts, United States

St. Joseph's Mercy Hospital

Ann Arbor, Michigan, United States

Oakwood Hospital and Medical Center

Dearborn, Michigan, United States

Spectrum Health

Grand Rapids, Michigan, United States

St. Luke's Hospital

Kansas City, Missouri, United States

Barnes Jewish Hospital

St Louis, Missouri, United States

Nebraska Heart Institute

Lincoln, Nebraska, United States

Nebraska Medical Center

Omaha, Nebraska, United States

Morristown Medical Center

Morristown, New Jersey, United States

St. Peter's Hospital

Albany, New York, 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

Saint Francis Hospital/The Heart Center

Roslyn, New York, United States

Mission Hospital

Asheville, North Carolina, United States

Moses H. Cone Memorial Hospital

Greensboro, North Carolina, United States

Duke University Hospital

Raleigh, North Carolina, 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

ProMedica Toledo Hospital

Toledo, Ohio, United States

Oklahoma Heart Hospital

Oklahoma City, Oklahoma, United States

Lehigh Valley Hospital

Allentown, Pennsylvania, United States

St. Thomas Heart

Nashville, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Baylor Hospital

Dallas, Texas, United States

The Heart Hospital Baylor Plano

Plano, Texas, United States

University of Virginia Health System

Charlottesville, Virginia, United States

Franciscan Health System Res. Center

Tacoma, Washington, United States

Aurora Saint Luke's Medical Center

Milwaukee, Wisconsin, United States

University of Alberta Hospital

Edmonton, Alberta, 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, Canada

Hamilton Health Sciences

Hamilton, Ontario, Canada

London Health Sciences Center, University Hospital

London, Ontario, Canada

Southlake Regional Health Center

Newmarket, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

McGill University Health Centre-Royal Victoria Hospital

Montreal, Quebec, Canada

Montreal Heart Institute

Montreal, Quebec, Canada

Institute universitaire de cardiologie et pneumologie de Quebec

Québec, , Canada

Countries

United States; Canada

References

Verma S, Rathwell S, Fremes S, Zheng Y, Mehta R, Lopes RD, Alexander JH, Goodman SG, Diepen SV; LEVO-CTS investigators. Associated factors and clinical outcomes in mechanical circulatory support use in patients undergoing high risk on-pump cardiac surgery: Insights from the LEVO-CTS trial. Am Heart J. 2022 Jun;248:35-41. doi: 10.1016/j.ahj.2022.02.013. Epub 2022 Mar 7.

Reference Type: DERIVED

PMID: 35263653 (View on PubMed)

Mehta RH, Leimberger JD, van Diepen S, Meza J, Wang A, Jankowich R, Harrison RW, Hay D, Fremes S, Duncan A, Soltesz EG, Luber J, Park S, Argenziano M, Murphy E, Marcel R, Kalavrouziotis D, Nagpal D, Bozinovski J, Toller W, Heringlake M, Goodman SG, Levy JH, Harrington RA, Anstrom KJ, Alexander JH; LEVO-CTS Investigators. Levosimendan in Patients with Left Ventricular Dysfunction Undergoing Cardiac Surgery. N Engl J Med. 2017 May 25;376(21):2032-2042. doi: 10.1056/NEJMoa1616218. Epub 2017 Mar 19.

Reference Type: DERIVED

PMID: 28316276 (View on PubMed)

Mehta RH, Van Diepen S, Meza J, Bokesch P, Leimberger JD, Tourt-Uhlig S, Swartz M, Parrotta J, Jankowich R, Hay D, Harrison RW, Fremes S, Goodman SG, Luber J, Toller W, Heringlake M, Anstrom KJ, Levy JH, Harrington RA, Alexander JH; LEVO-CTS Investigators. Levosimendan in patients with left ventricular systolic dysfunction undergoing cardiac surgery on cardiopulmonary bypass: Rationale and study design of the Levosimendan in Patients with Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass (LEVO-CTS) trial. Am Heart J. 2016 Dec;182:62-71. doi: 10.1016/j.ahj.2016.09.001. Epub 2016 Sep 9.

Reference Type: DERIVED

PMID: 27914501 (View on PubMed)

Lim JY, Deo SV, Rababa'h A, Altarabsheh SE, Cho YH, Hang D, McGraw M, Avery EG, Markowitz AH, Park SJ. Levosimendan Reduces Mortality in Adults with Left Ventricular Dysfunction Undergoing Cardiac Surgery: A Systematic Review and Meta-analysis. J Card Surg. 2015 Jul;30(7):547-54. doi: 10.1111/jocs.12562. Epub 2015 May 19.

Reference Type: DERIVED

PMID: 25989324 (View on PubMed)

Toller W, Heringlake M, Guarracino F, Algotsson L, Alvarez J, Argyriadou H, Ben-Gal T, Cerny V, Cholley B, Eremenko A, Guerrero-Orriach JL, Jarvela K, Karanovic N, Kivikko M, Lahtinen P, Lomivorotov V, Mehta RH, Music S, Pollesello P, Rex S, Riha H, Rudiger A, Salmenpera M, Szudi L, Tritapepe L, Wyncoll D, Owall A. Preoperative and perioperative use of levosimendan in cardiac surgery: European expert opinion. Int J Cardiol. 2015 Apr 1;184:323-336. doi: 10.1016/j.ijcard.2015.02.022. Epub 2015 Feb 24.

Reference Type: DERIVED

PMID: 25734940 (View on PubMed)

Other Identifiers

TNX-LVO-01

Identifier Type: -

Identifier Source: org_study_id