NCT06993584

Pharmacokinetic Modelling of Levosimendan in Adults

Pharmacokinetic Modelling of Levosimendan in Adults in Cardiogenic Shock With or Without Extracorporeal Membrane Oxygenation Support

• Status: Not Yet Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 100 (estimated)
• Sponsor: University Hospital, Rouen · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Cardiogenic shock is a pathological condition characterised by cardiac failure inducing tissue hypoxia and organ hypoperfusion, which can lead to multiple organ failure and death. Extracorporeal membrane oxygenation (ECMO) is a circulatory support technique commonly used in the treatment of cardiogenic shock. This device reduces mortality in patients with refractory shock, i.e. those who do not respond, or only partially respond, to medical treatment including inotropic and vasopressor pharmacological support. ECMO is associated with significant pharmacokinetic (PK) changes related to volume of distribution (Vd) and clearance (CL), which may alter the efficacy of treatments. From a PK point of view, the addition of an extracorporeal circuit capable of sequestering and/or degrading drugs represents a challenge for dose adjustment. Levosimendan (LVSMD) is a drug authorised for the treatment of acute decompensated heart failure. It's a lipophilic drug (logP=2.16) and highly protein-bound (\>97%), two properties that favour its sequestration in the ECMO circuit \[2\]. This hypothesis is reinforced by the recent publication of a RIPH3 study evaluating the PK of levosimendan in neonates and children in intensive care, whether or not assisted by ECMO (NCT03681379, Bourgoin P, Duflot T, Clin Pharmacokinet). The rationale for this project is based on the following hypotheses: 1°) Beneficial effects on renal function, pulmonary congestion, physical capacity and cardiac output have been observed with levosimendan in the management of cardiogenic shock \[4\] 2°) The use of antibiotics could alter the metabolism of LVSMD leading to a defect in the synthesis of the active metabolite. 3°) LVSMD is beneficial during weaning from ECMO and the contradictions in previously published results \[5\] could be attributed to a reduced half-life of the drug and/or OR-1896 due to adsorption phenomena on the ECMO circuit making the treatment less effective.

Conditions

• Cardiogenic Shock

Interventions

Type	Name	Description
OTHER	Adult patients in cardiogenic shock	evaluate the elimination clearance of levosimendan (LVSMD) in the group without extracorporeal membrane oxygenation (ECMO) and in the group with ECMO.

Timeline

• Start date: 2025-07-01
• Primary completion: 2027-07-30
• Completion: 2027-08-31
• First posted: 2025-05-29
• Last updated: 2025-06-27

Locations

3 sites across 1 country: France