Levosimendan in Patients With Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery On Cardiopulmonary Bypass
LEVO-CTS
A Double-Blind, Randomized, Placebo-Controlled Study of Levosimendan in Patients With Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass
1 other identifier
interventional
882
2 countries
60
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jul 2014
60 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 18, 2013
CompletedFirst Posted
Study publicly available on registry
January 1, 2014
CompletedStudy Start
First participant enrolled
July 1, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2016
CompletedResults Posted
Study results publicly available
May 22, 2018
CompletedJune 21, 2018
May 1, 2018
2.3 years
December 18, 2013
November 2, 2017
May 22, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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
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 Outcomes (3)
Duration of Intensive Care Unit/Critical or Coronary Care Unit (ICU/CCU) (Days)
participants will be followed for during the participant's hospital stay up to 30 days
Incidence of Low Cardiac Output Syndrome (LCOS)
5 days
Postoperative Use of Secondary Inotrope
24 hours
Other Outcomes (2)
Occurrence of All-cause Mortality From Randomization Through Day 90
90 days
Rehospitalization for Any Cause Through Day 30
30 days
Study Arms (2)
Levosimendan
EXPERIMENTALlevosimendan 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Placebo
PLACEBO COMPARATORplacebo 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Interventions
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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.
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (60)
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
Related Publications (5)
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.
PMID: 35263653DERIVEDMehta 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.
PMID: 28316276DERIVEDMehta 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.
PMID: 27914501DERIVEDLim 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.
PMID: 25989324DERIVEDToller 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.
PMID: 25734940DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Rajendra Mehta, MD Study Principal Investigator
- Organization
- Duke Clinical Research Institute
Study Officials
- PRINCIPAL INVESTIGATOR
Rajendra Mehta, MD
Duke Clinical Research Institute
- STUDY CHAIR
John Alexander, MD
Duke Clinical Research Institute
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 18, 2013
First Posted
January 1, 2014
Study Start
July 1, 2014
Primary Completion
November 1, 2016
Study Completion
November 1, 2016
Last Updated
June 21, 2018
Results First Posted
May 22, 2018
Record last verified: 2018-05