Pharmacokinetic Modelling of Levosimendan in Adults

NCT06993584 | Not Yet Recruiting

• 2 other identifiers: 2022/0346/HP2025-A00556-43
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 3

Brief Summary

In the light of current knowledge of the PK of levosimendan and its use in ECMO weaning, deciphering the mechanisms of inter-individual variability in exposure and response to levosimendan appears essential in order to better stratify patients eligible or not for this therapy and to adapt the treatment of patients in cardiogenic shock, with or without ECMO support, accordingly. The aim of this project is to use an innovative pharmacokinetic modelling approach based on clinico-biological data to study the key factors that could contribute to treatment failure in cardiogenic shock and to integrate them quantitatively for dose individualisation. The aim of this project is to conduct a prospective, multicentre, observational, comparative analysis, with minimal risks and constraints, to determine the concentrations of levosimendan and its metabolites during patient management in order to develop a pharmacokinetic model.

Conditions

Cardiogenic Shock

Keywords

cardiogenic shock; levosimendan; pharmacokinetics; ECMO; extracorporeal membrane oxygenation; ECLS

Outcome Measures

Primary Outcomes (1)

• Elimination Clearance of Levosimendan (LVSMD) in Adult Patients in Cardiogenic Shock with Extracorporeal Membrane Oxygenation (ECMO)

  The clearance (CL) of Lévosimendan (LVSMD) will be determined by the ratio of the total dose administered to the exposure characterised by the area under the curve (AUC) over time (CL=Dose/AUC). In order to obtain an accurate estimate of the AUC, blood samples will be taken from a catheter already in place for the patient's therapeutic needs and will be taken at 0, 2, 6, 24, 26 and 32 hours after the start of an intravenous infusion of LVSMD at the dosage defined according to the recommendations in the Summary of Product Characteristics (SmPC).

  At enrollment visit, hour 1, 2 and 6 and at hour 24, 26 and 32 after enrollment visit

Secondary Outcomes (4)

• Success rate of weaning in the ECMO patient group

  Hour 72 after enrollment visit

• Hemodynamic success rate in the group without extracorporeal membrane oxygenation (ECMO)

  Hour 72 after enrollment visit

• Population-based pharmacokinetic model of LVSMD and its metabolites

  Hours 48, 72, 96, 120, 144, 168, 336 and 504 after enrollment visit

• Influence of a change in intestinal microbiota on the conversion of levosimendan into its active metabolite

  Two rectal swabs 24 hours apart, one at enrollment visit and one at hour 24 after enrollment visit

Interventions

Adult patients in cardiogenic shock OTHER

evaluate the elimination clearance of levosimendan (LVSMD) in the group without extracorporeal membrane oxygenation (ECMO) and in the group with ECMO.

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients treated with Lévosimendan (LVSMD) as part of their usual care for cardiogenic shock (60 with extracorporeal membrane oxygenation (ECMO) and 40 without ECMO)

You may qualify if:

• Patient between 18 and 75 years of age admitted to an intensive care unit,
• Weight ≥ 50 kg,
• Patient with cardiogenic shock defined by a SCAI stage C, D, or E score.
• The medical team plans to initiate LVSMD treatment as part of the management of cardiogenic shock, according to the recommendations in the Summary of Product Characteristics (SmPC),
• Expected life expectancy \> 48 hours,
• Patient affiliated with a social security scheme,
• Due to the life-threatening nature of cardiogenic shock, the patient or, where applicable, family members or trusted person are informed as soon as possible and their consent is requested for the possible continuation of this research. They may also object to the use of the patient's data (and blood samples) for this research.

You may not qualify if:

• Pregnant, childbearing, or breastfeeding women,
• Persons deprived of their liberty by an administrative or judicial decision, or persons placed under judicial protection/guardianship or curatorship.

Sponsors & Collaborators

• University Hospital, Rouen: lead
• University Hospital, Lille: collaborator
• Amiens University Hospital, France: collaborator

Study Sites (3)

Cardio-Thoracic-Vascular Resuscitation Department, university Hospital of Amiens

Amiens, 80054, France

Location

Anesthesia Clinic - Resuscitation, University Hospital of Lile

Lille, 59037, France

Location

Anesthesia-Resuscitation Department, University Rouen Hospital

Rouen, 76031, France

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

1 aliquot of the 2 mL EDTA blood tube and 1 aliquot of the 4 mL heparinised tube

MeSH Terms

Conditions

Shock, Cardiogenic

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Shock

Study Officials

• Thomas TD DUFLOT, PharmD

  pharmacology department, University Hospital of Rouen

  STUDY CHAIR

• Emmanuel BESNIER, MD, PHD

  anesthesiology, University Hospital of Rouen

  STUDY CHAIR

Central Study Contacts

Camille MOLKHOU, MD

CONTACT

02 32 88 78 42; camille.molkhou@chu-rouen.fr

Vincent VF FERRANTI, ARC

CONTACT

02 32 88 82 65; Vincent.Ferranti@chu-rouen.fr

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Target Duration: 28 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2025
• First Posted: May 29, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): August 31, 2027
• Last Updated: June 27, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)