Preoperative Levosimendan in CABG Patients With Poor LV Function

Coronary Artery Bypass Grafting Clinical Trial

— LICORN  

Official title:

Effects of Levosimendan Pretreatment in Patients With Low Ejection Fraction (40 % or Less) Undergoing CABG: a Randomised, Double Blind, Multicenter Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02184819
• Other study ID #: P110138
• Status: Completed
• Phase: Phase 3
• First received: October 23, 2013
• Last updated: February 24, 2016
• Start date: June 2013
• Est. completion date: November 2015

Study information

• Verified date: November 2015
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France:ANSM-The French National Agency for Medicines and Health Products Safety
• Study type: Interventional

Clinical Trial 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).

Description:

Background: Patients with an ejection fraction of less than 40% are at high risk of developing postoperative low cardiac output syndrome (LCOS). Despite the use of potent inotropic agents or even ventricular mechanical assist devices, the mortality rate of such patients remains very high (from 17 to 38%). Their hospital stay is also prolonged and the cost of care for this population is increased. Two studies have suggested that post-operative administration of levosimendan could reduce hospital length of stay and long term (Day180) mortality in patients with LCOS. In addition a few studies have also suggested that pre-operative infusion of levosimendan (pre-conditioning) could reduce the use of other inotropes and mechanical assist devices in patients at high risk of developing LCOS. Unfortunately, the data supporting the beneficial effects of levosimendan in high risk cardiac surgery patients is very limited. Main goal: To evaluate the efficacy of a pre-operative infusion of levosimendan in high risk patients (EF less than 40%) undergoing cardiac surgery (CABG or combined surgery: CABG and valve replacement) to improve outcome. Secondary goals: To evaluate: 1) the clinical safety of a pre-operative infusion of levosimendan, 2) the costs of care in the levosimendan and control groups. Experimental setup: Prospective, multicenter, randomized versus placebo, double-blind trial. Treatment modalities: levosimendan will be administered by the intravenous route, according to a continuous infusion of 0.1mcg/kg/min over 24 hours. Levosimendan infusion (0.1mcg/kg/min) will be started immediately after induction of anaesthesia. The delay between infusion start and skin incision can be estimated between 30 to 60 min. The investigators decided to skip the bolus infusion that is frequently associated with systemic hypotension, which may result in serious adverse events and protocol exclusion. Study duration and patient follow-up: Patients will be recruited over 23 months. Individual follow-up will last 6 months. Overall duration of study will be 29 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 335
• Est. completion date: November 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 18 Years and older

• scheduled for CABG with CPB

• with or without asociated cardiac repair

• ejection fraction less than 40%

• signed informed consent

Exclusion Criteria:

• 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.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Coronary Artery Bypass Grafting
• Left Ventricular Dysfonction

Intervention

Drug:
• levosimendan
24 hour continuous infusion at the rate of 0,1 µg/kg/min
• Placebo
24 hour infusion at a rate of 0,1 µg/kg/min assuming that it contains study drug

Locations

Country	Name	City	State
France	Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, France	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Ministry of Health, France

Country where clinical trial is conducted

France, 

References & Publications (3)

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. Erratum in: Anesth Analg. 2007 Jun;104(6):1544. Dosage error in article text. — View Citation

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. — View Citation

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. Epub 2006 Apr 4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	mortality at Day 28 and Day 180		180 postoperative days	Yes
Secondary	The need for inotropic agents beyond 24 hours following the end of levosimendan/placebo infusion		1 time during 24h beyond operative	No
Secondary	The description of renal replacement therapy during ICU stay	renal failure requiring renal replacement therapy may occur anytime within 12 hours following surgery and may last 1-2 weeks on average.	within the 28 days after ICU admission	No
Secondary	number of ventilator-free days and out-of-ICU days at Day 28.		28 postoperative days	No