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

Primary Purpose

Hypertension, Pulmonary, Cardiac Failure, Pulmonary Vascular Resistance Abnormality

Status
Recruiting
Phase
Not Applicable
Locations
Greece
Study Type
Interventional
Intervention
levosimendan at a dose of 6 mcg/kg
milrinone at a dose of 50 mcg/kg
Sponsored by
Aretaieion University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hypertension, Pulmonary focused on measuring pulmonary vascular resistance, pulmonary hypertension, vasodilators, milrinone, levosimendan, cardiopulmonary bypass

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Onassis Cardiac Surgery CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

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

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

Arm Description

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

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

Outcomes

Primary Outcome Measures

change from baseline in mean pulmonary arterial pressure (MPAP)
a Swan-Ganz catheter will be used for hemodynamic measurements
change from baseline in pulmonary vascular resistance (PVR)
a Swan-Ganz catheter will be used for hemodynamic measurements
change from baseline in mean arterial pressure (MAP)
a Swan-Ganz catheter will be used for hemodynamic measurements
change from baseline in systemic vascular resistance (SVR)
a Swan-Ganz catheter will be used for hemodynamic measurements
change from baseline in pulmonary capillary wedge pressure (PCWP)
a Swan-Ganz catheter will be used for hemodynamic measurements
change from baseline in cardiac output (CO)
a Swan-Ganz catheter will be used for hemodynamic measurements
change from baseline in tricuspid annular plane systolic excursion (TAPSE)
transthoracic and transesophageal echocardiography will be used for echocardiographic measurements
change from baseline in fractional area change
transthoracic and transesophageal echocardiography will be used for echocardiographic measurements
length of ICU stay
duration of patient stay in ICU in days
hospitalization time
duration of hospital stay after surgery in days

Secondary Outcome Measures

Full Information

First Posted
January 16, 2021
Last Updated
February 23, 2023
Sponsor
Aretaieion University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04718350
Brief Title
Treatment of Pulmonary Hypertension in High-risk Cardiac Surgery Patients Using Inhalational and Intravenous Agents
Acronym
levos-milr
Official Title
Comparison of Intravenous Levosimendan and Inhalational Milrinone in High Risk Cardiac Patients With Pulmonary Hypertension
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 27, 2021 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Aretaieion University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension, Pulmonary, Cardiac Failure, Pulmonary Vascular Resistance Abnormality
Keywords
pulmonary vascular resistance, pulmonary hypertension, vasodilators, milrinone, levosimendan, cardiopulmonary bypass

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intravenous administration of Levosimendan at a dosage of 6 mcg/kg after induction of anesthesia
Arm Type
Active Comparator
Arm Description
in this group, 6 mcg/kg of levosimendan will be administered intravenously after anesthesia induction, aiming at prevention of pulmonary hypertension post bypass
Arm Title
Inhalational administration of Milrinone at a dosage of 50 mcg/kg after induction of anesthesia
Arm Type
Active Comparator
Arm Description
in this group, 50 mcg/kg of milrinone will be administered via inhalation after anesthesia induction, aiming at prevention of pulmonary hypertension post bypass
Intervention Type
Drug
Intervention Name(s)
levosimendan at a dose of 6 mcg/kg
Other Intervention Name(s)
Group Levo
Intervention Description
levosimendan will be administered intravenously at a dose of 6 mcg/kg after anesthesia induction
Intervention Type
Drug
Intervention Name(s)
milrinone at a dose of 50 mcg/kg
Other Intervention Name(s)
Group Milri
Intervention Description
milrinone will be administered via inhalation at a dose of 50 mcg/kg after anesthesia induction
Primary Outcome Measure Information:
Title
change from baseline in mean pulmonary arterial pressure (MPAP)
Description
a Swan-Ganz catheter will be used for hemodynamic measurements
Time Frame
20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
Title
change from baseline in pulmonary vascular resistance (PVR)
Description
a Swan-Ganz catheter will be used for hemodynamic measurements
Time Frame
20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
Title
change from baseline in mean arterial pressure (MAP)
Description
a Swan-Ganz catheter will be used for hemodynamic measurements
Time Frame
20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
Title
change from baseline in systemic vascular resistance (SVR)
Description
a Swan-Ganz catheter will be used for hemodynamic measurements
Time Frame
20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
Title
change from baseline in pulmonary capillary wedge pressure (PCWP)
Description
a Swan-Ganz catheter will be used for hemodynamic measurements
Time Frame
20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
Title
change from baseline in cardiac output (CO)
Description
a Swan-Ganz catheter will be used for hemodynamic measurements
Time Frame
20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
Title
change from baseline in tricuspid annular plane systolic excursion (TAPSE)
Description
transthoracic and transesophageal echocardiography will be used for echocardiographic measurements
Time Frame
20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
Title
change from baseline in fractional area change
Description
transthoracic and transesophageal echocardiography will be used for echocardiographic measurements
Time Frame
20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
Title
length of ICU stay
Description
duration of patient stay in ICU in days
Time Frame
postoperatively, an average period of 7-10 days
Title
hospitalization time
Description
duration of hospital stay after surgery in days
Time Frame
postoperatively, up to 20 days after the operation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kassiani Theodoraki, PhD, DESA
Phone
+306974634162
Email
ktheodoraki@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kassiani Theodoraki, PhD, DESA
Organizational Affiliation
Aretaieion University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Onassis Cardiac Surgery Center
City
Athens
ZIP/Postal Code
17674
Country
Greece
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Theophani Antoniou, MD, PhD
Email
antoniou_fani@yahoo.gr
First Name & Middle Initial & Last Name & Degree
Panagiotis Ftikos, MD
Email
pftikos@yahoo.gr

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
28717881
Citation
Theodoraki K, Thanopoulos A, Rellia P, Leontiadis E, Zarkalis D, Perreas K, Antoniou T. A retrospective comparison of inhaled milrinone and iloprost in post-bypass pulmonary hypertension. Heart Vessels. 2017 Dec;32(12):1488-1497. doi: 10.1007/s00380-017-1023-2. Epub 2017 Jul 17.
Results Reference
background
PubMed Identifier
19151265
Citation
Haddad F, Couture P, Tousignant C, Denault AY. The right ventricle in cardiac surgery, a perioperative perspective: II. Pathophysiology, clinical importance, and management. Anesth Analg. 2009 Feb;108(2):422-33. doi: 10.1213/ane.0b013e31818d8b92.
Results Reference
background
PubMed Identifier
29979110
Citation
Hansen MS, Andersen A, Nielsen-Kudsk JE. Levosimendan in pulmonary hypertension and right heart failure. Pulm Circ. 2018 Jul-Sep;8(3):2045894018790905. doi: 10.1177/2045894018790905. Epub 2018 Jul 6.
Results Reference
background
PubMed Identifier
30052230
Citation
Kundra TS, Nagaraja PS, Bharathi KS, Kaur P, Manjunatha N. Inhaled levosimendan versus intravenous levosimendan in patients with pulmonary hypertension undergoing mitral valve replacement. Ann Card Anaesth. 2018 Jul-Sep;21(3):328-332. doi: 10.4103/aca.ACA_19_18.
Results Reference
background
PubMed Identifier
30612930
Citation
Elhassan A, Essandoh M. Inhaled Levosimendan for Pulmonary Hypertension Treatment During Cardiac Surgery: A Novel Application to Avoid Systemic Hypotension. J Cardiothorac Vasc Anesth. 2019 Apr;33(4):1169-1170. doi: 10.1053/j.jvca.2018.11.039. Epub 2018 Nov 28. No abstract available.
Results Reference
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Treatment of Pulmonary Hypertension in High-risk Cardiac Surgery Patients Using Inhalational and Intravenous Agents

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