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

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ClinicalTrials.gov Identifier: NCT02184819
Recruitment Status : Completed
First Posted : July 9, 2014
Last Update Posted : February 25, 2016
Sponsor:
Collaborator:
Ministry of Health, France
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
Coronary Artery Bypass Grafting Left Ventricular Dysfonction Drug: levosimendan Drug: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 335 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Effects of Levosimendan Pretreatment in Patients With Low Ejection Fraction (40 % or Less) Undergoing CABG: a Randomised, Double Blind, Multicenter Trial
Study Start Date : June 2013
Actual Primary Completion Date : June 2015
Actual Study Completion Date : November 2015

Arm Intervention/treatment
Active Comparator: levosimendan
study drug
Drug: levosimendan
24 hour continuous infusion at the rate of 0,1 µg/kg/min
Other Name: Simdax

Placebo Comparator: placebo
placebo group
Drug: Placebo
24 hour infusion at a rate of 0,1 µg/kg/min assuming that it contains study drug
Other Name: riboflavine




Primary Outcome Measures :
  1. Confirmed low cardiac output syndrome [ Time Frame: 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 :
  1. mortality at Day 28 and Day 180 [ Time Frame: 180 postoperative days ]
  2. The need for inotropic agents beyond 24 hours following the end of levosimendan/placebo infusion [ Time Frame: 1 time during 24h beyond operative ]
  3. The description of renal replacement therapy during ICU stay [ Time Frame: 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.

  4. number of ventilator-free days and out-of-ICU days at Day 28. [ Time Frame: 28 postoperative days ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02184819


Locations
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France
Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, France
Paris, France, 75015
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Ministry of Health, France
Investigators
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Principal Investigator: 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

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02184819    
Other Study ID Numbers: P110138
First Posted: July 9, 2014    Key Record Dates
Last Update Posted: February 25, 2016
Last Verified: November 2015
Keywords provided by Assistance Publique - Hôpitaux de Paris:
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
Additional relevant MeSH terms:
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Simendan
Physiological Effects of Drugs
Cardiotonic Agents
Vasodilator Agents
Phosphodiesterase 3 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protective Agents