Pharmacokinetics of Inhaled Levosimendan (Symbiov)

May 17, 2024 updated by: Universitair Ziekenhuis Brussel
Determination of biological availability, time-to-peak and elimination half-life of inhaled levosimendan by administration of an inhaled- and intravenous dose of levosimendan.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
6

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Levosimendan inhalation
Levosimendan 12µg/kg inhalation over 10 minutes, once
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.
Active Comparator: Levosimendan intravenous
Levosimendan 12µg/kg intravenous over 10 minutes, once
Drug: 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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Bioavailability of inhaled levosimendan
Time Frame: 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,
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
Time-to-peak of inhaled levosimendan
Time Frame: 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
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
Elimination half-life of inhaled levosimenan
Time Frame: 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
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Effect of inhaled levosimendan on MAP
Time Frame: 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)
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
Effect of inhaled levosimendan on TVR
Time Frame: 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)
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
Effect of inhaled levosimendan on CO
Time Frame: 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)
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
Effect of inhaled levosimendan on LVOT VTI
Time Frame: 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
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
Effect of inhaled levosimendan on FAC of the right vetricle
Time Frame: 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
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
Effect of inhaled levosimendan on S'
Time Frame: 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
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
Effect of inhaled levosimendan on SPAP
Time Frame: 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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Universitair Ziekenhuis Brussel

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Matthias Raes, MD, Universitair Ziekenhuis Brussel

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 9, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 23, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 29, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 20, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 17, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2022SIMBIOV

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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