Prophylactic Administration of Levosimendan in Patients Undergoing Coronary Surgery

NCT ID: NCT01318460

Last Updated: 2019-05-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2014-03-31

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.

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.

Conditions

Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Levosimendan

Patients treated with prophylactic administration of levosimendan

Group Type: ACTIVE_COMPARATOR

Levosimendan infusion

Intervention Type: DRUG

Prophylactic 24h infusion of levosimendan at a dose of 0.1 mg/kg/min

Placebo group

Patients managed with placebo administration

Group Type: PLACEBO_COMPARATOR

Placebo infusion

Intervention Type: DRUG

Twenty-four hour administration of placebo

Interventions

Levosimendan infusion

Prophylactic 24h infusion of levosimendan at a dose of 0.1 mg/kg/min

Intervention Type: DRUG

Placebo infusion

Twenty-four hour administration of placebo

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Orion Corporation, Orion Pharma

INDUSTRY

Sponsor Role: collaborator

AHEPA University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Kyriakos Anastasiadis

Head of Cardiothoracic Department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kyriakos Anastasiadis, MD, FETCS

Role: PRINCIPAL_INVESTIGATOR

AHEPA University Hospital

Christos Papakonstantinou, MD

Role: STUDY_CHAIR

AHEPA University Hospital

Locations

Department of Cardiothoracic Surgery, AHEPA University Hospital

Thessaloniki, , Greece

Countries

Greece

References

De Hert SG, Lorsomradee S, Cromheecke S, Van der Linden PJ. The effects of levosimendan in cardiac surgery patients with poor left ventricular function. Anesth Analg. 2007 Apr;104(4):766-73. doi: 10.1213/01.ane.0000256863.92050.d3.

Reference Type: BACKGROUND

PMID: 17377079 (View on PubMed)

Tasouli A, Papadopoulos K, Antoniou T, Kriaras I, Stavridis G, Degiannis D, Geroulanos S. Efficacy and safety of perioperative infusion of levosimendan in patients with compromised cardiac function undergoing open-heart surgery: importance of early use. Eur J Cardiothorac Surg. 2007 Oct;32(4):629-33. doi: 10.1016/j.ejcts.2007.07.010. Epub 2007 Aug 15.

Reference Type: BACKGROUND

PMID: 17702589 (View on PubMed)

Kolseth SM, Nordhaug DO, Stenseth R, Sellevold O, Kirkeby-Garstad I, Wahba A. Prophylactic treatment with levosimendan: a retrospective matched-control study of patients with reduced left ventricular function. Eur J Cardiothorac Surg. 2009 Dec;36(6):1024-30. doi: 10.1016/j.ejcts.2009.05.001. Epub 2009 Jul 9.

Reference Type: BACKGROUND

PMID: 19592266 (View on PubMed)

Other Identifiers

AHEPA_CTS-03

Identifier Type: -

Identifier Source: org_study_id