levos-milr: Treatment of Pulmonary Hypertension in High-risk Cardiac Surgery Patients Using Inhalational and Intravenous Agents

Sponsor

Aretaieion University Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04718350

Collaborator

(none)

Enrollment

Location

Arms

22.1

Anticipated Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of this study is to examine and compare the effect of Levosimendan and Milrinone administered intravenously and via inhalation respectively in cardiac surgery patients with pulmonary hypertension and right ventricular dysfunction.

Condition or Disease	Intervention/Treatment	Phase
Hypertension, Pulmonary Cardiac Failure Pulmonary Vascular Resistance Abnormality	Drug: levosimendan at a dose of 6 mcg/kg Drug: milrinone at a dose of 50 mcg/kg	N/A

Detailed 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, the intravenous administration of Levosimendan will be compared with the inhalational use of milrinone in patients with pulmonary hypertension undergoing cardiac surgery.

In this setting, 40 patients with PH caused by left sided heart disease, will be assigned into two groups:

GROUP A: Intravenous administration of Levosimendan in dosage 6mcg/kg after induction of anesthesia.

GROUP B: Inhalational administration of milrinone in dosage 50mcg/kg after induction of anesthesia.

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.

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Comparison of Intravenous Levosimendan and Inhalational Milrinone in High Risk Cardiac Patients With Pulmonary Hypertension

Actual Study Start Date :

Jan 27, 2021

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Intravenous administration of Levosimendan at a dosage of 6 mcg/kg after induction of anesthesia in this group, 6 mcg/kg of levosimendan will be administered intravenously after anesthesia induction, aiming at prevention of pulmonary hypertension post bypass	Drug: levosimendan at a dose of 6 mcg/kg levosimendan will be administered intravenously at a dose of 6 mcg/kg after anesthesia induction Other Names: Group Levo
Active Comparator: Inhalational administration of Milrinone at a dosage of 50 mcg/kg after induction of anesthesia in this group, 50 mcg/kg of milrinone will be administered via inhalation after anesthesia induction, aiming at prevention of pulmonary hypertension post bypass	Drug: milrinone at a dose of 50 mcg/kg milrinone will be administered via inhalation at a dose of 50 mcg/kg after anesthesia induction Other Names: Group Milri

Arm

Intervention/Treatment

Active Comparator: Intravenous administration of Levosimendan at a dosage of 6 mcg/kg after induction of anesthesia

in this group, 6 mcg/kg of levosimendan will be administered intravenously after anesthesia induction, aiming at prevention of pulmonary hypertension post bypass

Drug: levosimendan at a dose of 6 mcg/kg

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

Other Names:

Group Levo

Active Comparator: Inhalational administration of Milrinone at a dosage of 50 mcg/kg after induction of anesthesia

in this group, 50 mcg/kg of milrinone will be administered via inhalation after anesthesia induction, aiming at prevention of pulmonary hypertension post bypass

Drug: milrinone at a dose of 50 mcg/kg

milrinone will be administered via inhalation at a dose of 50 mcg/kg after anesthesia induction

Other Names:

Group Milri

Outcome Measures

Primary Outcome Measures

change from baseline in mean pulmonary arterial pressure (MPAP) [20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission]
a Swan-Ganz catheter will be used for hemodynamic measurements
change from baseline in pulmonary vascular resistance (PVR) [20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission]
a Swan-Ganz catheter will be used for hemodynamic measurements
change from baseline in mean arterial pressure (MAP) [20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission]
a Swan-Ganz catheter will be used for hemodynamic measurements
change from baseline in systemic vascular resistance (SVR) [20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission]
a Swan-Ganz catheter will be used for hemodynamic measurements
change from baseline in pulmonary capillary wedge pressure (PCWP) [20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission]
a Swan-Ganz catheter will be used for hemodynamic measurements
change from baseline in cardiac output (CO) [20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission]
a Swan-Ganz catheter will be used for hemodynamic measurements
change from baseline in tricuspid annular plane systolic excursion (TAPSE) [20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission]
transthoracic and transesophageal echocardiography will be used for echocardiographic measurements
change from baseline in fractional area change [20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission]
transthoracic and transesophageal echocardiography will be used for echocardiographic measurements
length of ICU stay [postoperatively, an average period of 7-10 days]
duration of patient stay in ICU in days
hospitalization time [postoperatively, up to 20 days after the operation]
duration of hospital stay after surgery in days