Levosimendan Administration in Pulmonary Hypertension (Levosim-PH)

Aretaieion University Hospital

Status: Completed

Conditions: Pulmonary Vascular Resistance Abnormality; Cardiac Failure; Hypertension, Pulmonary

Treatments: Drug: levosimendan at a dose of 3 mcg/kg; Drug: levosimendan at a dose of 12 mcg/kg; Drug: levosimendan at a dose of 6 mcg/kg

Study type: Interventional

Funder types: Other

Identifiers

NCT04599816

annie-panagiotis

Details and patient eligibility

About

The aim of the study is to examine the pharmacokinetics and pharmacodynamic properties of Levosimendan in cardiac surgery patients with pulmonary hypertension and impaired right ventricular function.

Full description

Pulmonary hypertension (PH) is a pathophysiological disorder hemodynamically characterized by increased pulmonary vascular resistance and pressure. This can lead to right ventricle pressure overload and failure which is worsened by cardiopulmonary bypass (CPB) and extracorporeal circulation and is accompanied by high rates of morbidity and mortality in cardiac surgery patients. Pharmacological agents used to decrease pulmonary vascular resistance and right ventricle afterload are prostaglandins, iloprost, milrinone, nitric oxide (NO) and recently Levosimendan. These agents can be administered intravenously or via inhalation.

In this study, Levosimendan will be administered in patients with pulmonary hypertension undergoing cardiac surgery. The aim of the study is to examine the pharmacokinetics and pharmacodynamic properties of Levosimendan in cardiac surgery patients with pulmonary hypertension and impaired right ventricular function. The drug will be administered in different doses to define the dose at which Levosimendan administration reduces pulmonary vascular resistance and pressure without causing significant reduction of systemic vascular resistance and pressure. The anti-inflammatory effect of the perioperative use of Levosimendan in cardiac surgery will also be studied.

In this setting, 45 patients with PH caused by left sided heart disease, will be assigned into three groups:

GROUP A: Administration of Levosimendan at a dosage of 3mcg/kg after anesthesia induction.

GROUP B: Administration of Levosimendan at a dosage of 6mcg/kg after anesthesia induction.

GROUP C: Administration of Levosimendan at a dosage of 12mcg/kg after anesthesia induction.

Before and after the administration of the drug, heart function will be evaluated by hemodynamic measurements obtained by the Swan-Ganz catheter. These parameters will be heart rate (HR), blood pressure (BP), mean pulmonary arterial pressure (MPAP), central venous pressure (CVP), cardiac output (CO), pulmonary capillary wedge pressure (PCWP), cardiac index (CI), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR). Transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE) will also be used. The anti-inflammatory action of Levosimendan will also be evaluated by interleukin-6 (IL-6) measurements.

This study will lead to conclusions regarding the effectiveness of Levosimendan administration in the treatment of right heart failure and PH in cardiac surgery patients.

Enrollment: 45 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• patients with pulmonary hypertension due to left ventricular dysfunction based on echocardiographic diagnosis preoperatively
• elective cardiac surgery

Exclusion criteria

• primary pulmonary hypertension
• thromboembolic disease
• chronic obstructive pulmonary disease
• emergency surgery
• redo surgery
• inability to consent to the study

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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45 participants in 3 patient groups

levosimendan administration at a dose of 3 mcg/kg after anesthesia induction

Active Comparator group

Description:

levosimendan will be administered at a dose of 3 mcg/kg after anesthesia induction

Treatment:

Drug: levosimendan at a dose of 3 mcg/kg

levosimendan administration at a dose of 6 mcg/kg after anesthesia induction

Active Comparator group

Description:

levosimendan will be administered at a dose of 6 mcg/kg after anesthesia induction

Treatment:

Drug: levosimendan at a dose of 6 mcg/kg

levosimendan administration at a dose of 12 mcg/kg after anesthesia induction

Active Comparator group

Description:

levosimendan will be administered at a dose of 12 mcg/kg after anesthesia induction

Treatment:

Drug: levosimendan at a dose of 12 mcg/kg