Preoperative Levosimendan in CABG Patients With Poor LV Function

Phase 3

Completed

• Conditions: Coronary Artery Bypass Grafting; Left Ventricular Dysfonction
• Interventions: Drug: levosimendan; Drug: Placebo

• Registration Number: NCT02184819
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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).

Detailed 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.

Study Timeline

• Study Start: 2013-06
• Study First Submitted: 2013-10-23
• Study First Submitted QC: 2014-07-03
• Study First Posted: 2014-07-09
• Primary Completion: 2015-06
• Status Verified: 2015-11
• Study Completion: 2015-11
• Last Update Submitted: 2016-02-24
• Last Update Posted: 2016-02-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 335

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
levosimendan	levosimendan	study drug
placebo	Placebo	placebo group

Primary Outcome Measures

Name	Time	Method
Confirmed low cardiac output syndrome	within the 28 days after ICU admission	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

Secondary Outcome Measures

Name	Time	Method
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	renal failure requiring renal replacement therapy may occur anytime within 12 hours following surgery and may last 1-2 weeks on average.
number of ventilator-free days and out-of-ICU days at Day 28.	28 postoperative days

Trial Locations

Locations (1)

Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, France; 🇫🇷 Paris, France