Preoperative Levosimendan in CABG Patients With Poor LV Function (LICORN)

Assistance Publique - Hôpitaux de Paris

Status and phase: Completed; Phase 3

Conditions: Left Ventricular Dysfonction; Coronary Artery Bypass Grafting

Treatments: Drug: Placebo; Drug: levosimendan

Study type: Interventional

Funder types: Other

Identifiers

NCT02184819

P110138

Details and patient eligibility

About

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).

Full 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.

Enrollment: 335 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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335 participants in 2 patient groups, including a placebo group

levosimendan

Active Comparator group

Description:

study drug

Treatment:

Drug: levosimendan

placebo

Placebo Comparator group

Description:

placebo group

Treatment:

Drug: Placebo