Preoperative Levosimendan in CABG Patients With Poor LV Function

NCT02184819 | Completed Phase 3 DMC

• 1 other identifier: P110138
• Study Type: interventional
• Target: 335
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators want to test the hypothesis that an infusion of levosimendan started prior to CABG surgery can reduce incidence and severity of low cardiac output syndrome in patients with poor LV function (EF 40% or less).

Conditions

Coronary Artery Bypass Grafting; Left Ventricular Dysfonction

Keywords

coronary artery bypass graft; left ventricular dysfunction; low cardiac output syndrome; levosimendan; mortality; inotropic agents; cardiac mechanical assist devices; renal replacement therapy; mechanical ventilation duration; ICU stay

Outcome Measures

Primary Outcomes (1)

• Confirmed low cardiac output syndrome

  Composite of the three following items:the need for inotropic agents beyond 24 hours following the end of levosimendan/placebo infusion; the need for post-operative mechanical assist devices (intra-aortic balloon pump: IABP, extra-corporeal life support: ECLS) or failure to wean from these techniques if they were inserted pre-operatively; the need for renal replacement therapy during ICU stay

  within the 28 days after ICU admission

Secondary Outcomes (4)

• mortality at Day 28 and Day 180

  180 postoperative days

• The need for inotropic agents beyond 24 hours following the end of levosimendan/placebo infusion

  1 time during 24h beyond operative

• The description of renal replacement therapy during ICU stay

  within the 28 days after ICU admission

• number of ventilator-free days and out-of-ICU days at Day 28.

  28 postoperative days

Study Arms (2)

levosimendan

ACTIVE COMPARATOR

study drug

Drug: levosimendan

placebo

PLACEBO COMPARATOR

placebo group

Drug: Placebo

Interventions

levosimendan DRUG

24 hour continuous infusion at the rate of 0,1 µg/kg/min

Also known as: Simdax

levosimendan

Placebo DRUG

24 hour infusion at a rate of 0,1 µg/kg/min assuming that it contains study drug

Also known as: riboflavine

placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Years and older
• scheduled for CABG with CPB
• with or without asociated cardiac repair
• ejection fraction less than 40%
• signed informed consent

You may not qualify if:

• preoperative renal failure (creatinine clearance less than 30 ml/min)
• liver failure (prothrombine time less than 50% in the absence of vitamin K antagonist)
• cardiac surgery without CABG
• pregnancy
• emergency surgery
• known allergy to levosimendan
• severe hypotension prior to surgery
• severe tachycardia
• prior history of torsade de pointe
• dynamic obstruction od left ventricular outflow tract
• lack of signed informed consent.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Ministry of Health, France: collaborator

Study Sites (1)

Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, France

Paris, 75015, France

Location

Related Publications (5)

• Levin R, Degrange M, Del Mazo C, Tanus E, Porcile R. Preoperative levosimendan decreases mortality and the development of low cardiac output in high-risk patients with severe left ventricular dysfunction undergoing coronary artery bypass grafting with cardiopulmonary bypass. Exp Clin Cardiol. 2012 Sep;17(3):125-30.

  PMID: 23620700 BACKGROUND

• De Hert SG, Lorsomradee S, Cromheecke S, Van der Linden PJ. The effects of levosimendan in cardiac surgery patients with poor left ventricular function. Anesth Analg. 2007 Apr;104(4):766-73. doi: 10.1213/01.ane.0000256863.92050.d3.

  PMID: 17377079 BACKGROUND

• Tritapepe L, De Santis V, Vitale D, Santulli M, Morelli A, Nofroni I, Puddu PE, Singer M, Pietropaoli P. Preconditioning effects of levosimendan in coronary artery bypass grafting--a pilot study. Br J Anaesth. 2006 Jun;96(6):694-700. doi: 10.1093/bja/ael082. Epub 2006 Apr 4.

  PMID: 16595616 BACKGROUND

• Cholley B, Caruba T, Grosjean S, Amour J, Ouattara A, Villacorta J, Miguet B, Guinet P, Levy F, Squara P, Ait Hamou N, Carillion A, Boyer J, Boughenou MF, Rosier S, Robin E, Radutoiu M, Durand M, Guidon C, Desebbe O, Charles-Nelson A, Menasche P, Rozec B, Girard C, Fellahi JL, Pirracchio R, Chatellier G; -. Effect of Levosimendan on Low Cardiac Output Syndrome in Patients With Low Ejection Fraction Undergoing Coronary Artery Bypass Grafting With Cardiopulmonary Bypass: The LICORN Randomized Clinical Trial. JAMA. 2017 Aug 8;318(6):548-556. doi: 10.1001/jama.2017.9973.

  PMID: 28787507 DERIVED

• Caruba T, Hourton D, Sabatier B, Rousseau D, Tibi A, Hoffart-Jourdain C, Souag A, Freitas N, Yjjou M, Almeida C, Gomes N, Aucouturier P, Djadi-Prat J, Menasche P, Chatellier G, Cholley B. Rationale and design of the multicenter randomized trial investigating the effects of levosimendan pretreatment in patients with low ejection fraction (</=40 %) undergoing CABG with cardiopulmonary bypass (LICORN study). J Cardiothorac Surg. 2016 Aug 5;11(1):127. doi: 10.1186/s13019-016-0530-z.

  PMID: 27496105 DERIVED

MeSH Terms

Conditions

Ventricular Dysfunction, Left; Cardiac Output, Low

Interventions

Simendan; Riboflavin

Condition Hierarchy (Ancestors)

Ventricular Dysfunction; Heart Diseases; Cardiovascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hydrazones; Hydrazines; Organic Chemicals; Pyridazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Flavins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Coenzymes; Enzymes and Coenzymes; Pigments, Biological; Biological Factors

Study Officials

• Bernard Cholley, MD, PhD

  Anesthesiology and Intensive Care, Hopital Européen Georges Pompidou, Paris, France

  PRINCIPAL INVESTIGATOR

• Thibaut Caruba, PharmD

  Pharmacy department, Hopital Européen Georges Pompidou, Paris, France

  PRINCIPAL INVESTIGATOR

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: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2013
• First Posted: July 9, 2014
• Study Start: June 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: November 1, 2015
• Last Updated: February 25, 2016

Record last verified: 2015-11

Locations

FR (1)