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Levosimendan Administration in Pulmonary Hypertension (Levosim-PH)

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ClinicalTrials.gov Identifier: NCT04599816
Recruitment Status : Recruiting
First Posted : October 23, 2020
Last Update Posted : January 20, 2021
Sponsor:
Information provided by (Responsible Party):
Dr Kassiani Theodoraki, Aretaieion University Hospital

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.

Condition or disease Intervention/treatment Phase
Hypertension, Pulmonary Cardiac Failure Pulmonary Vascular Resistance Abnormality Drug: levosimendan at a dose of 3 mcg/kg Drug: levosimendan at a dose of 6 mcg/kg Drug: levosimendan at a dose of 12 mcg/kg Not Applicable

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, 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Levosimendan Administration in High Risk Cardiac Surgery Patients With Pulmonary Hypertension
Actual Study Start Date : October 17, 2020
Estimated Primary Completion Date : October 17, 2022
Estimated Study Completion Date : October 17, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: 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
Drug: levosimendan at a dose of 3 mcg/kg
levosimendan will be administered intravenously at a dose of 3 mcg/kg after anesthesia induction

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

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




Primary Outcome Measures :
  1. change from baseline in mean pulmonary arterial pressure (MPAP) [ Time Frame: 20 minutes after levosimendan administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission ]
    a Swan-Ganz catheter will be used for hemodynamic measurements


Secondary Outcome Measures :
  1. change from baseline in pulmonary vascular resistance (PVR) [ Time Frame: 20 minutes after levosimendan administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission ]
    a Swan-Ganz catheter will be used for hemodynamic measurements

  2. change from baseline in mean arterial pressure (MAP) [ Time Frame: 20 minutes after levosimendan administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission ]
    a Swan-Ganz catheter will be used for hemodynamic measurements

  3. change from baseline in systemic vascular resistance (SVR) [ Time Frame: 20 minutes after levosimendan administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission ]
    a Swan-Ganz catheter will be used for hemodynamic measurements

  4. change from baseline in pulmonary capillary wedge pressure (PCWP) [ Time Frame: 20 minutes after levosimendan administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission ]
    a Swan-Ganz catheter will be used for hemodynamic measurements

  5. change from baseline in cardiac output (CO) [ Time Frame: 20 minutes after levosimendan administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission ]
    a Swan-Ganz catheter will be used for hemodynamic measurements

  6. change from baseline in tricuspid annular plane systolic excursion (TAPSE) [ Time Frame: 20 minutes after levosimendan administration, at the end of surgery, 2 hours after Intensive Care Unit (ICU) admission and 80 hours after levosimendan administration ]
    transthoracic and transesophageal echocardiography will be used for echocardiographic measurements

  7. change from baseline in fractional area change [ Time Frame: 20 minutes after levosimendan administration, at the end of surgery, 2 hours after Intensive Care Unit (ICU) admission and 80 hours after levosimendan administration ]
    transthoracic and transesophageal echocardiography will be used for echocardiographic measurements


Other Outcome Measures:
  1. change from baseline in blood levels of levosimendan [ Time Frame: 20 minutes, 6 hours, 12 hours, 24 hours and 80 hours after administration ]
    blood levels will be measured with liquid chromatography

  2. change from baseline in blood levels of interleukin-6 (IL-6) [ Time Frame: end of surgery, 6 hours, 12 hours and 24 hours after Intensive Care Unit (ICU) admission ]
    blood levels will be measured with the enzyme linked immunosorbent assay (ELISA)



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04599816


Contacts
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Contact: Kassiani Theodoraki, PhD, DESA +306974634162 ktheodoraki@hotmail.com

Locations
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Greece
Onassis Cardiac Surgery Center Recruiting
Athens, Greece, 17674
Contact: Theophani Antoniou, MD, PhD       antoniou_fani@yahoo.gr   
Contact: Panagiotis Ftikos, MD       pftikos@yahoo.gr   
Sponsors and Collaborators
Aretaieion University Hospital
Investigators
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Principal Investigator: Kassiani Theodoraki, PhD, DESA Aretaieion University Hospital
Publications:

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Responsible Party: Dr Kassiani Theodoraki, Professor of Anesthesiology, Aretaieion University Hospital
ClinicalTrials.gov Identifier: NCT04599816    
Other Study ID Numbers: annie-panagiotis
First Posted: October 23, 2020    Key Record Dates
Last Update Posted: January 20, 2021
Last Verified: January 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Dr Kassiani Theodoraki, Aretaieion University Hospital:
pulmonary vascular resistance
pulmonary hypertension
vasodilators
cardiopulmonary bypass
Additional relevant MeSH terms:
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Hypertension, Pulmonary
Hypertension
Heart Failure
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Heart Diseases
Simendan
Cardiotonic Agents
Vasodilator Agents
Phosphodiesterase 3 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs