Levosimendan Administration in Pulmonary Hypertension

NCT ID: NCT04599816

Last Updated: 2023-02-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

45 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-10-17

Study Completion Date

2022-10-17

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Hypertension, Pulmonary Cardiac Failure Pulmonary Vascular Resistance Abnormality

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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

Group Type ACTIVE_COMPARATOR

levosimendan at a dose of 3 mcg/kg

Intervention Type DRUG

levosimendan will be administered intravenously at a dose of 3 mcg/kg after anesthesia induction

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

Group Type ACTIVE_COMPARATOR

levosimendan at a dose of 6 mcg/kg

Intervention Type DRUG

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

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

Group Type ACTIVE_COMPARATOR

levosimendan at a dose of 12 mcg/kg

Intervention Type DRUG

levosimendan will be administered intravenously at a dose of 12 mcg/kg after anesthesia induction

Interventions

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levosimendan at a dose of 3 mcg/kg

levosimendan will be administered intravenously at a dose of 3 mcg/kg after anesthesia induction

Intervention Type DRUG

levosimendan at a dose of 6 mcg/kg

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

Intervention Type DRUG

levosimendan at a dose of 12 mcg/kg

levosimendan will be administered intravenously at a dose of 12 mcg/kg after anesthesia induction

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Aretaieion University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Dr Kassiani Theodoraki

Professor of Anesthesiology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Kassiani Theodoraki, PhD, DESA

Role: PRINCIPAL_INVESTIGATOR

Aretaieion University Hospital

Locations

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Onassis Cardiac Surgery Center

Athens, , Greece

Site Status

Countries

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Greece

References

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Theodoraki K, Rellia P, Thanopoulos A, Tsourelis L, Zarkalis D, Sfyrakis P, Antoniou T. Inhaled iloprost controls pulmonary hypertension after cardiopulmonary bypass. Can J Anaesth. 2002 Nov;49(9):963-7. doi: 10.1007/BF03016884.

Reference Type BACKGROUND
PMID: 12419726 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28717881 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19151265 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29979110 (View on PubMed)

Boost KA, Hoegl S, Dolfen A, Czerwonka H, Scheiermann P, Zwissler B, Hofstetter C. Inhaled levosimendan reduces mortality and release of proinflammatory mediators in a rat model of experimental ventilator-induced lung injury. Crit Care Med. 2008 Jun;36(6):1873-9. doi: 10.1097/CCM.0b013e3181743e63.

Reference Type BACKGROUND
PMID: 18496375 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30052230 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30612930 (View on PubMed)

Zhang J, Gage EM, Ji QC, El-Shourbagy TA. A strategy for high-throughput analysis of levosimendan and its metabolites in human plasma samples using sequential negative and positive ionization liquid chromatography/tandem mass spectrometric detection. Rapid Commun Mass Spectrom. 2007;21(14):2169-76. doi: 10.1002/rcm.3046.

Reference Type BACKGROUND
PMID: 17631672 (View on PubMed)

Other Identifiers

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annie-panagiotis

Identifier Type: -

Identifier Source: org_study_id

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