Clinical trial NCT06387862: Pharmacokinetics of Inhaled Levosimendan
Official title: Pharmacokinetics of Inhaled Levosimendan
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Left Ventricular Dysfunction
Keywords: levosimendan
inhalation
pharmakokinetic
Lead sponsor: Universitair Ziekenhuis Brussel
Sponsor class: OTHER
First posted: 2024-04-29
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Bioavailability of inhaled levosimendan
timeFrame: 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
measure: Time-to-peak of inhaled levosimendan
timeFrame: 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
measure: Elimination half-life of inhaled levosimenan
timeFrame: 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 outcomes:
measure: Effect of inhaled levosimendan on MAP
timeFrame: 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
measure: Effect of inhaled levosimendan on TVR
timeFrame: 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
measure: Effect of inhaled levosimendan on CO
timeFrame: 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
measure: Effect of inhaled levosimendan on LVOT VTI
timeFrame: 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
measure: Effect of inhaled levosimendan on FAC of the right vetricle
timeFrame: 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
measure: Effect of inhaled levosimendan on S'
timeFrame: 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
measure: Effect of inhaled levosimendan on SPAP
timeFrame: 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
Other outcomes:
Locations:
city: Brussel
country: Belgium
facility: UZ Brussel
Study officials:
affiliation: Universitair Ziekenhuis Brussel
name: Matthias Raes, MD
role: PRINCIPAL_INVESTIGATOR
References: