Prophylactic Administration of Levosimendan in Patients Undergoing Coronary Surgery

This study has been completed.
Sponsor:
Collaborator:
Orion Corporation, Orion Pharma
Information provided by (Responsible Party):
Kyriakos Anastasiadis, AHEPA University Hospital
ClinicalTrials.gov Identifier:
NCT01318460
First received: March 17, 2011
Last updated: March 11, 2014
Last verified: March 2014
  Purpose

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 Intervention Phase
Coronary Artery Disease
Drug: Levosimendan infusion
Drug: Placebo infusion
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Prophylactic Administration of Levosimendan in Patients With Impaired Left Ventricular Function Undergoing Coronary Surgery

Resource links provided by NLM:


Further study details as provided by AHEPA University Hospital:

Primary Outcome Measures:
  • Left ventricular function [ Time Frame: Seventh postoperative day ] [ Designated as safety issue: No ]
    Left ventricular function as assessed by transthoracic or transesophageal echocardiography on the seventh postoperative day


Secondary Outcome Measures:
  • Perioperative mortality [ Time Frame: 30 days postoperatively ] [ Designated as safety issue: No ]
  • Need for intraaortic balloon pump [ Time Frame: 1st-7th postoperative day ] [ Designated as safety issue: No ]
  • Inotropic support [ Time Frame: 1st-7th postoperative day ] [ Designated as safety issue: No ]
    Need for high inotropic support

  • Total ICU stay [ Time Frame: 1st-7th postoperative day ] [ Designated as safety issue: No ]
  • Total length of hospital stay [ Time Frame: 1st-7th postoperative day ] [ Designated as safety issue: No ]
  • Time on mechanical ventilation [ Time Frame: 1st-7th postoperative day ] [ Designated as safety issue: No ]
  • Major adverse cardiovascular events [ Time Frame: 1st-7th postoperative day ] [ Designated as safety issue: No ]
    Perioperative myocardial infarction, stroke, need for revascularization)

  • Morbidity [ Time Frame: 1st-7th postoperative day ] [ Designated as safety issue: No ]

Enrollment: 32
Study Start Date: March 2011
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01318460

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

Publications:
Responsible Party: Kyriakos Anastasiadis, Head of Cardiothoracic Department, AHEPA University Hospital
ClinicalTrials.gov Identifier: NCT01318460     History of Changes
Other Study ID Numbers: AHEPA_CTS-03
Study First Received: March 17, 2011
Last Updated: March 11, 2014
Health Authority: Greece: Ethics Committee

Keywords provided by AHEPA University Hospital:
coronary artery disease
levosimendan
coronary artery bypass grafting
cardiac surgery

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

ClinicalTrials.gov processed this record on July 08, 2014