Left Ventricular Dysfunction
Conditions
Keywords
levosimendan, inhalation, pharmakokinetic
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.
Interventions
DRUGLevosimendan 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.
DRUGLevosimendan 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
Sponsors
Universitair Ziekenhuis Brussel
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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 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 |
| 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 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) |
Countries
Belgium
Contacts
Primary ContactMatthias Raes, MD
Backup ContactMarie-Claire Van Malderen, SC
Outcome results
None listed