Pharmacokinetics of Inhaled Levosimendan

Phase 2

Recruiting

• Conditions: Left Ventricular Dysfunction
• Interventions: Drug: Levosimendan 2.5 milligram/milliliter Injectable Solutiondose Inhaled; Drug: Levosimendan 2.5 milligram/milliliter Injectable Solutiondose Intravenous

• Registration Number: NCT06387862
• Lead Sponsor: Universitair Ziekenhuis Brussel

Brief 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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2023-10
• Study First Submitted: 2024-01-09
• Study Start: 2024-02-01
• Study First Submitted QC: 2024-04-23
• Study First Posted: 2024-04-29
• Last Update Submitted: 2024-05-17
• Last Update Posted: 2024-05-20
• Primary Completion: 2024-11
• Study Completion: 2025-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 6

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%)

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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 β-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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Levosimendan inhalation	Levosimendan 2.5 milligram/milliliter Injectable Solutiondose Inhaled	Levosimendan 12µg/kg inhalation over 10 minutes, once
Levosimendan intravenous	Levosimendan 2.5 milligram/milliliter Injectable Solutiondose Intravenous	Levosimendan 12µg/kg intravenous over 10 minutes, once

Primary Outcome Measures

Name	Time	Method
Bioavailability of inhaled levosimendan	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	Assessment of bioavailability of inhaled levosimendan in spontaneous breathing patients,
Time-to-peak of inhaled levosimendan	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	Assessment of time-to-peak plasma concentration of inhaled levosimendan in spontaneous breathing patients
Elimination half-life of inhaled levosimenan	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	Assessment of elimination half-life of inhaled levosimendan in spontaneous breathing patients

Secondary Outcome Measures

Name	Time	Method
Effect of inhaled levosimendan on 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	Assessment of effect of inhaled levosimendan on invasively-measured hemodynamic parameter Cardiac Output (CO)
Effect of inhaled levosimendan on LVOT VTI	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	Assessment of effect of inhaled levosimendan on echocardiography-derived parameter left -ventricular-outflow-tract (LVOT) velocity-time-integral (VTI) as marker for cardiac output
Effect of inhaled levosimendan on SPAP	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	Assessment of effect of inhaled levosimendan on echocardiography-derived parameter (SPAP) systolic pulmonary artery pressure
Effect of inhaled levosimendan on 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	Assessment of effect of inhaled levosimendan on invasively-measured hemodynamic parameter total vascular resistance (TVR)
Effect of inhaled levosimendan on FAC of the right vetricle	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	Assessment of effect of inhaled levosimendan on echocardiography-derived parameter Fractional-Area-Change (FAC) of the right ventricle as marker of right ventricular function
Effect of inhaled levosimendan on 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	Assessment of effect of inhaled levosimendan on invasively-measured hemodynamic parameter mean arterial blood pressure (MAP)
Effect of inhaled levosimendan on S'	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	Assessment of effect of inhaled levosimendan on echocardiography-derived parameter S' wave velocity as marker of right ventricular function

Trial Locations

Locations (1)

UZ Brussel; 🇧🇪 Brussel, Belgium