Levosimendan Administration in Pulmonary Hypertension

NCT04599816 | Completed

• 1 other identifier: annie-panagiotis
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hypertension, Pulmonary; Cardiac Failure; Pulmonary Vascular Resistance Abnormality

Keywords

pulmonary vascular resistance; pulmonary hypertension; vasodilators; cardiopulmonary bypass

Outcome Measures

Primary Outcomes (1)

• change from baseline in mean pulmonary arterial pressure (MPAP)

  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 Outcomes (7)

• change from baseline in pulmonary vascular resistance (PVR)

  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)

  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)

  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)

  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)

  20 minutes after levosimendan administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission

Other Outcomes (2)

• change from baseline in blood levels of levosimendan

  20 minutes, 6 hours, 12 hours, 24 hours and 80 hours after administration

• change from baseline in blood levels of interleukin-6 (IL-6)

  end of surgery, 6 hours, 12 hours and 24 hours after Intensive Care Unit (ICU) admission

Study Arms (3)

levosimendan administration at a dose of 3 mcg/kg after anesthesia induction

ACTIVE COMPARATOR

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

Drug: levosimendan at a dose of 3 mcg/kg

levosimendan administration at a dose of 6 mcg/kg after anesthesia induction

ACTIVE COMPARATOR

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

Drug: levosimendan at a dose of 6 mcg/kg

levosimendan administration at a dose of 12 mcg/kg after anesthesia induction

ACTIVE COMPARATOR

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

Drug: levosimendan at a dose of 12 mcg/kg

Interventions

levosimendan at a dose of 3 mcg/kg DRUG

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

levosimendan administration at a dose of 3 mcg/kg after anesthesia induction

levosimendan at a dose of 6 mcg/kg DRUG

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

levosimendan administration at a dose of 6 mcg/kg after anesthesia induction

levosimendan at a dose of 12 mcg/kg DRUG

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

levosimendan administration at a dose of 12 mcg/kg after anesthesia induction

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients with pulmonary hypertension due to left ventricular dysfunction based on echocardiographic diagnosis preoperatively
• elective cardiac surgery

You may not qualify if:

• primary pulmonary hypertension
• thromboembolic disease
• chronic obstructive pulmonary disease
• emergency surgery
• redo surgery
• inability to consent to the study

Sponsors & Collaborators

• Aretaieion University Hospital: lead

Study Sites (1)

Onassis Cardiac Surgery Center

Athens, 17674, Greece

Location

Related Publications (8)

• 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.

  PMID: 12419726 BACKGROUND

• 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.

  PMID: 28717881 BACKGROUND

• 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.

  PMID: 19151265 BACKGROUND

• 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.

  PMID: 29979110 BACKGROUND

• 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.

  PMID: 18496375 BACKGROUND

• 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.

  PMID: 30052230 BACKGROUND

• 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.

  PMID: 30612930 BACKGROUND

• 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.

  PMID: 17631672 BACKGROUND

MeSH Terms

Conditions

Hypertension, Pulmonary; Heart Failure

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Heart Diseases

Study Officials

• Kassiani Theodoraki, PhD, DESA

  Aretaieion University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Anesthesiology

Study Record Dates

• First Submitted: October 18, 2020
• First Posted: October 23, 2020
• Study Start: October 17, 2020
• Primary Completion: October 17, 2022
• Study Completion: October 17, 2022
• Last Updated: February 8, 2023

Record last verified: 2023-02

Locations

GR (1)