Levosimendans Pharmacokinetics in Intensive Care Patients. An Observational Study. (LEFKIP)

Levosimendans Pharmacokinetics in Intensive Care Patients

Evaluation of the pharmacokinetics of levosimendan and its metabolites in intensive care patients with normal, reduced and dialysis supported renal function.

Study Overview

• Status: Recruiting
• Conditions: Renal Failure; Acute Kidney Injury; Pharmacokinetics; Intensive Care; Metabolites
• Intervention / Treatment: Other: No intervention

Detailed Description

Aims: To gain a better understanding of the pharmacokinetics of Levosimendan in critically ill patients and in particular in those patients with and without renal failure and in those receiving CRRT. This project may give a better basis to determine whether dose monitoring and adjustment of Levosimendan is necessary to avoid toxicity or under treatment. In order to study Levosimendan pharmacokinetics, the Karolinska laboratory has in parallel developed a method for analysis of the substance and its metabolites.

Research questions:

1. To what extent are Levosimendan and its active metabolites dialysable in patients receiving continuous renal replacement therapy.
2. How do the concentrations of Levosimendan and its active metabolites differ in critically ill patients with and without acute renal failure?

Method:

The is a prospective observational study conducted on adult intensive care units at Karolinska University Hospital.

Study Population: Critical care patients who due to clinical need are prescribed Levosimendan by treating physician will be included into one of three groups based on degree of AKI (KDIGO classification) and need for CRRT. This is a non-interventional study.

Number of patients to be included: we intend to include 4-12 patients per group.

Procedure: The decision to prescribe Levosimendan will be made by treating physicians as will decisions regarding dose, dose adjustment and length of treatment.

Screening for inclusion will occur when a decision to prescribe Levosimendan has been made.

Samples of blood, urine and ultrafiltration fluid from the CRRT circuit are to be analysed to determine concentration of Levosimendan and its metabolites. Plasma concentrations will be obtained, before and after the dialysis filter.

Concentration monitoring will occur over a period of up to 6 days, with test taken at 0, 6 and 20 hours after infusion start and after cessation of Levosimendan every two hours for the first 10 hours and there after twice a day for the next 5 days. A maximum of 30 samples (15 in non CRRT patients) of 1-3ml are taken.

Patient groups:

Group 1: Levosimendan + no AKI or KDIGO AKI stage 1. Group 2: Levosimendan + KDIGO AKI stage 2-3, not CRRT Group 3: Levosimendan + KDIGO AKI stage 1-3 with CRRT.

Analysis:

Analysis of the plasma concentration of Levosimendan and its metabolites (OR-1896, OR-1855) is performed at the clinical pharmacology department, Karolinska University Hospital. Reference substances have been provided by Orion Pharma.

Definitions:

Acute Kidney Failure (AKI) is defined according to the KDIGO definition: Creatinine entry from the baseline (percentage increase) and volume of urine production or CRRT treatment.

• Study Type: Observational
• Enrollment (Anticipated): 12

Contacts and Locations

• Study Contact: Name: Claire Rimes-Stigare, MD, PhD; Phone Number: 004651770000; Email: claire.rimes-stigare@regionstockholm.se
• Study Contact Backup: Name: Susanne Rysz, MD, PhD; Phone Number: 004651770000; Email: susanne.rysz@regionstockholm.se

Study Locations

• Sweden
  • Stockholm, Sweden
    • Recruiting
    • Karolinska University Hospital
    • Contact: Claire Rimes-Stigare, MD, PhD; Phone Number: 004651770000; Email: claire.rimes-stigare@regionstockholm.se
    • Contact: Susanne, MD; Phone Number: 004651770000; Email: sussanne.rysz@regionstockholm.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Intensive Care Unit patients in whom the treating physician has decided due to clinical indication to administer levosimendan. Dose and length of treatment decided by treating physician.

With Group 1: No renal failure or Acute Kidney Injury(AKI)* stage 1. Group 2: AKI stage 2-3, not receiving renal replacement therapy. Group 3: Receiving continuous renal replacement therapy (CRRT)

*AKI classification system Kidney Disease Improving Global outcomes (KDIGO)

Description

Inclusion Criteria:

° Adult Intensive care patients in whom treating physicians have judged to be in need of Levosimendan treatment.

Exclusion Criteria:

• Patient <18 years of age
• Pregnancy
• Patients receiving Intermittent hemodialysis

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of levosimendan and OR 1896 1855 in plasma	Plasma concentrations of levosimendan and its active metabolites afte Levosimendan infusion.	1-5 days

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Collaborators: Karolinska University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: September 30, 2021
• First Submitted That Met QC Criteria: October 12, 2021
• First Posted (Actual): October 13, 2021

Study Record Updates

• Last Update Posted (Actual): October 13, 2021
• Last Update Submitted That Met QC Criteria: October 12, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Acute Kidney Injury
• Other Study ID Numbers: 4-1951/2021

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No