Prophylactic Administration of Levosimendan in Patients Undergoing Coronary Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01318460
Recruitment Status : Completed
First Posted : March 18, 2011
Last Update Posted : March 12, 2014
Orion Corporation, Orion Pharma
Information provided by (Responsible Party):
Kyriakos Anastasiadis, AHEPA University Hospital

Brief Summary:
The present pilot study aims to investigate the effectiveness of the preoperative infusion of levosimendan in patients with impaired left ventricular function undergoing coronary artery bypass grafting.

Condition or disease Intervention/treatment Phase
Coronary Artery Disease Drug: Levosimendan infusion Drug: Placebo infusion Phase 4

Detailed Description:

Myocardial revascularization in patients with impaired left ventricular function remains a serious problem in cardiac surgery. Despite the recent developments with the use of new surgical techniques (mini-extracorporeal circulation, off pump surgery) the perioperative morbidity and mortality are relatively high. Therapeutic solutions with the use of inotropic drugs, as adrenergic agonists and phosphodiesterase inhibitors, have offered important improvement to the hemodynamic status of these patients, but they have not considerably decreased mortality. These drugs owe their positive inotropic action to the increase of intracellular calcium and thereafter they improve the myocardial function.

Levosimendan (SIMDAX) is a new calcium sensitizer which increases the myocardial contractility without particular promotion of the intracellular calcium accumulation. Contemporary experimental and clinical data demonstrated the effectiveness of this drug in the reduction of surgical mortality to the patients with low left ventricular ejection fraction (LVEF) who undergo coronary artery bypass grafting (CABG).

This is an original prospective randomized controlled study focused on the preoperative use of this drug in patients with impaired left ventricular function which is associated with a high operative risk (i.e. EuroSCORE). Perioperative myocardial stunning is particularly evident in this cohort of patients. Prophylactic administration of levosimendan the day before the operation could be translated in improved myocardial performance intraoperatively and during the early postoperative period.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Prophylactic Administration of Levosimendan in Patients With Impaired Left Ventricular Function Undergoing Coronary Surgery
Study Start Date : March 2011
Primary Completion Date : March 2014
Study Completion Date : March 2014

Arm Intervention/treatment
Active Comparator: Levosimendan
Patients treated with prophylactic administration of levosimendan
Drug: Levosimendan infusion
Prophylactic 24h infusion of levosimendan at a dose of 0.1 mg/kg/min
Placebo Comparator: Placebo group
Patients managed with placebo administration
Drug: Placebo infusion
Twenty-four hour administration of placebo

Primary Outcome Measures :
  1. Left ventricular function [ Time Frame: Seventh postoperative day ]
    Left ventricular function as assessed by transthoracic or transesophageal echocardiography on the seventh postoperative day

Secondary Outcome Measures :
  1. Perioperative mortality [ Time Frame: 30 days postoperatively ]
  2. Need for intraaortic balloon pump [ Time Frame: 1st-7th postoperative day ]
  3. Inotropic support [ Time Frame: 1st-7th postoperative day ]
    Need for high inotropic support

  4. Total ICU stay [ Time Frame: 1st-7th postoperative day ]
  5. Total length of hospital stay [ Time Frame: 1st-7th postoperative day ]
  6. Time on mechanical ventilation [ Time Frame: 1st-7th postoperative day ]
  7. Major adverse cardiovascular events [ Time Frame: 1st-7th postoperative day ]
    Perioperative myocardial infarction, stroke, need for revascularization)

  8. Morbidity [ Time Frame: 1st-7th postoperative day ]

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • coronary artery disease which warrants myocardial revascularization with coronary artery bypass grafting according to current guidelines
  • age < 79 years old
  • left ventricular ejection fraction <= 40%
  • informed patient's consent

Exclusion Criteria:

  • age < 18 years old
  • emergency surgery
  • medical history of acute myocardial infarction with ST elevation (STEMI) less than 14 days old
  • any severe comorbidity which increases the perioperative risk (i.e. neoplasia, rheumatoid arthritis, chronic obstructive pulmonary disease)
  • need for valvular replacement surgery
  • redo surgery
  • serum creatinine > 2 mg/dl
  • history of malignant cardiac arrhythmias

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 identifier (NCT number): NCT01318460

Department of Cardiothoracic Surgery, AHEPA University Hospital
Thessaloniki, Greece, 546 36
Sponsors and Collaborators
AHEPA University Hospital
Orion Corporation, Orion Pharma
Principal Investigator: Kyriakos Anastasiadis, MD, FETCS AHEPA University Hospital
Study Chair: Christos Papakonstantinou, MD AHEPA University Hospital

Responsible Party: Kyriakos Anastasiadis, Head of Cardiothoracic Department, AHEPA University Hospital Identifier: NCT01318460     History of Changes
Other Study ID Numbers: AHEPA_CTS-03
First Posted: March 18, 2011    Key Record Dates
Last Update Posted: March 12, 2014
Last Verified: March 2014

Keywords provided by Kyriakos Anastasiadis, AHEPA University Hospital:
coronary artery disease
coronary artery bypass grafting
cardiac surgery

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arterial Occlusive Diseases
Vascular Diseases
Anti-Arrhythmia Agents
Cardiotonic Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Protective Agents
Physiological Effects of Drugs