Levosimendan Administration in Pulmonary Hypertension (Levosim-PH)

February 5, 2023 updated by: Dr Kassiani Theodoraki, Aretaieion University Hospital

Levosimendan Administration in High Risk Cardiac Surgery Patients With Pulmonary Hypertension

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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, 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.

Study Type

Interventional

Enrollment (Actual)

45

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Greece
      • Athens, Greece, 17674
        • Onassis Cardiac Surgery Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: levosimendan administration at a dose of 3 mcg/kg after anesthesia induction
levosimendan will be administered at a dose of 3 mcg/kg after anesthesia induction
Drug: levosimendan at a dose of 3 mcg/kg
levosimendan will be administered intravenously at a dose of 3 mcg/kg after anesthesia induction
ACTIVE_COMPARATOR: levosimendan administration at a dose of 6 mcg/kg after anesthesia induction
levosimendan will be administered at a dose of 6 mcg/kg after anesthesia induction
Drug: levosimendan at a dose of 6 mcg/kg
levosimendan will be administered intravenously at a dose of 6 mcg/kg after anesthesia induction
ACTIVE_COMPARATOR: levosimendan administration at a dose of 12 mcg/kg after anesthesia induction
levosimendan will be administered at a dose of 12 mcg/kg after anesthesia induction
Drug: levosimendan at a dose of 12 mcg/kg
levosimendan will be administered intravenously at a dose of 12 mcg/kg after anesthesia induction

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
change from baseline in mean pulmonary arterial pressure (MPAP)
Time Frame: 20 minutes after levosimendan 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
20 minutes after levosimendan administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
change from baseline in pulmonary vascular resistance (PVR)
Time Frame: 20 minutes after levosimendan 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
20 minutes after levosimendan administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
change from baseline in mean arterial pressure (MAP)
Time Frame: 20 minutes after levosimendan 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
20 minutes after levosimendan administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
change from baseline in systemic vascular resistance (SVR)
Time Frame: 20 minutes after levosimendan 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
20 minutes after levosimendan administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
change from baseline in pulmonary capillary wedge pressure (PCWP)
Time Frame: 20 minutes after levosimendan 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
20 minutes after levosimendan administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
change from baseline in cardiac output (CO)
Time Frame: 20 minutes after levosimendan 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
20 minutes after levosimendan administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
change from baseline in tricuspid annular plane systolic excursion (TAPSE)
Time Frame: 20 minutes after levosimendan administration, at the end of surgery, 2 hours after Intensive Care Unit (ICU) admission and 80 hours after levosimendan administration
transthoracic and transesophageal echocardiography will be used for echocardiographic measurements
20 minutes after levosimendan administration, at the end of surgery, 2 hours after Intensive Care Unit (ICU) admission and 80 hours after levosimendan administration
change from baseline in fractional area change
Time Frame: 20 minutes after levosimendan administration, at the end of surgery, 2 hours after Intensive Care Unit (ICU) admission and 80 hours after levosimendan administration
transthoracic and transesophageal echocardiography will be used for echocardiographic measurements
20 minutes after levosimendan administration, at the end of surgery, 2 hours after Intensive Care Unit (ICU) admission and 80 hours after levosimendan administration

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
change from baseline in blood levels of levosimendan
Time Frame: 20 minutes, 6 hours, 12 hours, 24 hours and 80 hours after administration
blood levels will be measured with liquid chromatography
20 minutes, 6 hours, 12 hours, 24 hours and 80 hours after administration
change from baseline in blood levels of interleukin-6 (IL-6)
Time Frame: end of surgery, 6 hours, 12 hours and 24 hours after Intensive Care Unit (ICU) admission
blood levels will be measured with the enzyme linked immunosorbent assay (ELISA)
end of surgery, 6 hours, 12 hours and 24 hours after Intensive Care Unit (ICU) admission

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Aretaieion University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 17, 2020

Primary Completion (ACTUAL)

October 17, 2022

Study Completion (ACTUAL)

October 17, 2022

Study Registration Dates

First Submitted

October 18, 2020

First Submitted That Met QC Criteria

October 22, 2020

First Posted (ACTUAL)

October 23, 2020

Study Record Updates

Last Update Posted (ACTUAL)

February 8, 2023

Last Update Submitted That Met QC Criteria

February 5, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • annie-panagiotis

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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