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

Hypertension, Pulmonary Clinical Trial

— levos-milr  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04718350
• Other study ID #: levo-milri
• Status: Recruiting
• Phase: N/A
• Start date: January 27, 2021
• Est. completion date: December 2023

Study information

• Verified date: February 2023
• Source: Aretaieion University Hospital
• Contact: Kassiani Theodoraki, PhD, DESA
• Phone: +306974634162
• Email: ktheodoraki[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiac Failure
• Heart Failure
• Hypertension
• Hypertension, Pulmonary
• Pulmonary Vascular Resistance Abnormality

Intervention

Drug:
• levosimendan at a dose of 6 mcg/kg
levosimendan will be administered intravenously at a dose of 6 mcg/kg after anesthesia induction
• milrinone at a dose of 50 mcg/kg
milrinone will be administered via inhalation at a dose of 50 mcg/kg after anesthesia induction

Locations

Country	Name	City	State
Greece	Onassis Cardiac Surgery Center	Athens

Sponsors (1)

Lead Sponsor	Collaborator
Aretaieion University Hospital

Country where clinical trial is conducted

Greece, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

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