Pharmacokinetics of Inhaled Levosimendan

Left Ventricular Dysfunction Clinical Trial

— Symbiov  

Official title:

Pharmacokinetics of Inhaled Levosimendan

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06387862
• Other study ID #: 2022SIMBIOV
• Status: Recruiting
• Phase: Phase 2
• Start date: February 1, 2024
• Est. completion date: January 2025

Study information

• Verified date: October 2023
• Source: Universitair Ziekenhuis Brussel
• Contact: Matthias Raes, MD
• Phone: 024749872
• Email: matthias.raes[@]uzbrussel.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Determination of biological availability, time-to-peak and elimination half-life of inhaled levosimendan by administration of an inhaled- and intravenous dose of levosimendan.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 6
• Est. completion date: January 2025
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subject >18 years of age

• Scheduled for elective coronary artery bypass grafting (CABG)

• Provided written informed consent

• Impaired left ventricular function (LVEF <40%)

Exclusion Criteria:

• Known allergy for levosimendan or solutes

• Persistent angina, defined as Canadian Cardiovascular Society score > I

• History of valvular intervention or uncorrected primary stenotic valve disease

• Uncorrected thyroid disease

• Infiltrative, hypertrophic or restrictive cardiomyopathy

• Pericardial disease

• Active myocarditis

• Chronic obstructive pulmonary disease requiring long-term treatment with ß-agonists, Theophylline, or corticosteroids (FEV1 < 80%; Tiffeneau-index <0.7)

• History of serious arrhythmias, defined as a history of ventricular tachycardia or fibrillation other than that occurring within 24 hours after acute myocardial infarction (MI)

• resting heart rate > 115 bpm for at least 10 minutes on repeated measurements

• Supine systolic blood pressure < 85 mm Hg or >200 mm Hg

• patients with implanted pacemaker/defibrillator or cardiac resynchronisation therapy (CRT-device)

• primary renal or hepatic impairment (creatinine > 2.5 mg/dL or aspartate aminotransferase/alanine aminotransferase >2 times upper limit of normal and/or increased level of bilirubin (> 2 times the upper limit of normal and increase of international normalised ratio (INR) above the upper limit of normal, respectively)

• Uncorrected hypokalemia or hyperkalemia (potassium <3.5 mmol/L or >5.5 mmol/L)

• Uncorrected hypomagnesemia (magnesium <0.65mmol/L)

• Treatment with another investigational agent within 30 days before study entry

• Intubated and mechanically ventilated at the time of study entry

Related Conditions & MeSH terms

• Left Ventricular Dysfunction
• Ventricular Dysfunction
• Ventricular Dysfunction, Left

Intervention

Drug:
• Levosimendan 2.5 milligram/milliliter Injectable Solutiondose Inhaled
Each patient will receive 12µg/kg of levosimendan by inhalation over 10 min. During 10h following inhaled dose, plasma concentrations will be measured.
• Levosimendan 2.5 milligram/milliliter Injectable Solutiondose Intravenous
Each patient will receive 12µg/kg of levosimendan by intravenous (IV) administration over 10 min and at the same timepoints plasma samples will be measured

Locations

Country	Name	City	State
Belgium	UZ Brussel	Brussel

Sponsors (1)

Lead Sponsor	Collaborator
Universitair Ziekenhuis Brussel

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bioavailability of inhaled levosimendan	Assessment of bioavailability of inhaled levosimendan in spontaneous breathing patients,	Baseline, plasma samples at 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1hour 30 minutes, 2 hours , 3 hours , 6 hours, 10 hours after end of infusion/inhalation
Primary	Time-to-peak of inhaled levosimendan	Assessment of time-to-peak plasma concentration of inhaled levosimendan in spontaneous breathing patients	Baseline, plasma samples at 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1hour 30 minutes, 2 hours , 3 hours , 6 hours, 10 hours after end of infusion/inhalation
Primary	Elimination half-life of inhaled levosimenan	Assessment of elimination half-life of inhaled levosimendan in spontaneous breathing patients	Baseline, plasma samples at 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1hour 30 minutes, 2 hours , 3 hours , 6 hours, 10 hours after end of infusion/inhalation
Secondary	Effect of inhaled levosimendan on MAP	Assessment of effect of inhaled levosimendan on invasively-measured hemodynamic parameter mean arterial blood pressure (MAP)	Baseline, plasma samples at 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1hour 30 minutes, 2 hours , 3 hours , 6 hours, 10 hours after end of infusion/inhalation
Secondary	Effect of inhaled levosimendan on TVR	Assessment of effect of inhaled levosimendan on invasively-measured hemodynamic parameter total vascular resistance (TVR)	Baseline, plasma samples at 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1hour 30 minutes, 2 hours , 3 hours , 6 hours, 10 hours after end of infusion/inhalation
Secondary	Effect of inhaled levosimendan on CO	Assessment of effect of inhaled levosimendan on invasively-measured hemodynamic parameter Cardiac Output (CO)	Baseline, plasma samples at 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1hour 30 minutes, 2 hours , 3 hours , 6 hours, 10 hours after end of infusion/inhalation
Secondary	Effect of inhaled levosimendan on LVOT VTI	Assessment of effect of inhaled levosimendan on echocardiography-derived parameter left -ventricular-outflow-tract (LVOT) velocity-time-integral (VTI) as marker for cardiac output	Baseline, plasma samples at 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1hour 30 minutes, 2 hours , 3 hours , 6 hours, 10 hours after end of infusion/inhalation
Secondary	Effect of inhaled levosimendan on FAC of the right vetricle	Assessment of effect of inhaled levosimendan on echocardiography-derived parameter Fractional-Area-Change (FAC) of the right ventricle as marker of right ventricular function	Baseline, plasma samples at 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1hour 30 minutes, 2 hours , 3 hours , 6 hours, 10 hours after end of infusion/inhalation
Secondary	Effect of inhaled levosimendan on S'	Assessment of effect of inhaled levosimendan on echocardiography-derived parameter S' wave velocity as marker of right ventricular function	Baseline, plasma samples at 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1hour 30 minutes, 2 hours , 3 hours , 6 hours, 10 hours after end of infusion/inhalation
Secondary	Effect of inhaled levosimendan on SPAP	Assessment of effect of inhaled levosimendan on echocardiography-derived parameter (SPAP) systolic pulmonary artery pressure	Baseline, plasma samples at 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1hour 30 minutes, 2 hours , 3 hours , 6 hours, 10 hours after end of infusion/inhalation