Clinical trial NCT04718350: Treatment of Pulmonary Hypertension in High-risk Cardiac Surgery Patients Using Inhalational and Intravenous Agents
Official title: Comparison of Intravenous Levosimendan and Inhalational Milrinone in High Risk Cardiac Patients With Pulmonary Hypertension
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hypertension, Pulmonary
Cardiac Failure
Pulmonary Vascular Resistance Abnormality
Keywords: pulmonary vascular resistance
pulmonary hypertension
vasodilators
milrinone
levosimendan
cardiopulmonary bypass
Lead sponsor: Aretaieion University Hospital
Sponsor class: OTHER
First posted: 2021-01-22
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: change from baseline in mean pulmonary arterial pressure (MPAP)
timeFrame: 20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
measure: change from baseline in pulmonary vascular resistance (PVR)
timeFrame: 20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
measure: change from baseline in mean arterial pressure (MAP)
timeFrame: 20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
measure: change from baseline in systemic vascular resistance (SVR)
timeFrame: 20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
measure: change from baseline in pulmonary capillary wedge pressure (PCWP)
timeFrame: 20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
measure: change from baseline in cardiac output (CO)
timeFrame: 20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
measure: change from baseline in tricuspid annular plane systolic excursion (TAPSE)
timeFrame: 20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
measure: change from baseline in fractional area change
timeFrame: 20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
measure: length of ICU stay
timeFrame: postoperatively, an average period of 7-10 days
measure: hospitalization time
timeFrame: postoperatively, up to 20 days after the operation
Secondary outcomes:
Other outcomes:
Locations:
city: Athens
country: Greece
facility: Onassis Cardiac Surgery Center
Study officials:
affiliation: Aretaieion University Hospital
name: Kassiani Theodoraki, PhD, DESA
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.