The ECMOCYP (cytochromes P450 Activity) Study

Recruiting

• Conditions: Cardiogenic Shock; Temporary Mechanical Circulatory Support; ECMO

• Registration Number: NCT06662084
• Lead Sponsor: University Hospital, Geneva

Brief Summary

Prospective open label observational study including patients requiring a tMCS (VA-ECMO or Impella® CP) or in in cardiogenic shock according to the SCAI (Society for Cardiovascular Angiography and Interventions) ESC (European Society of Cardiology) definition 41,42 and not requiring or not eligible to tMCS (ECMO, Impella®, intra-aortic balloon pump) (control group).

Detailed Description

The Geneva cocktail will be administered on 2 occasions at D3 after tMCS implantation (or start of the cardiogenic shock) and 14 days after tMCS explantation (or cardiogenic shock termination defined as: no need to use inortropic or vasopressive agent and absence of organ insufficiency)

Primary endpoint:

* Evaluate the impact of tMCS on the activity of CYPs as measured with metabolic ratios MRs (CYP activity at

* D3 post tMCS implantation and 14 days after tMCS explantation vs the activity of CYPs in the control group.

Secondary endpoints:

* Evaluate the correlation between the activity of CYPs and IL-6 levels

* Evaluate the correlation between the activity of CYPs and CRP levels

* Evaluate the correlation between the activity of CYPs and TNF-α levels

* Evaluate the correlation between the activity of CYPs and IL-1β levels

* Evaluate the correlation between the activity of CYPs and IFN-γ levels

* Compare CYP activity vs expected CYP activity based on patients' CYP genotyping

* Compare CYP activity between VA-EMCO and micro-axial pump device (Impella® CP)

Study Timeline

• Study First Submitted: 2024-09-13
• Status Verified: 2024-10
• Study Start: 2024-10
• Study First Submitted QC: 2024-10-25
• Last Update Submitted: 2024-10-25
• Study First Posted: 2024-10-28
• Last Update Posted: 2024-10-28
• Primary Completion: 2026-07
• Study Completion: 2026-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 46

Inclusion Criteria

• Male and female patients presenting a refractory cardiogenic shock, requiring temporary mechanical circulatory support (tMCS), with either the use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) or a micro-axial pump device (Impella® CP).
• Male and female patients in cardiogenic shock according to the SCAI (Society for Cardiovascular Angiography and Interventions) ESC (European Society of Cardiology) definition and not requiring or not eligible to temporary mechanical circulatory support (tMCS). (e.g. ECMO, Impella®, intra-aortic balloon pump) (control group)
• Age > 18 years old
• Comprehension of French
• Ability to give consent (consent will be sought from the therapeutic representative or from relatives as the patient will be sedated and intubated. Definitive consent will be sought at patient's second blood sample planned after tMCS explantation (in case of patient's favorable outcome).

Exclusion Criteria

• Male and female patients presenting a refractory ARDS requiring veno-venous extracorporeal membrane oxygenation (VV-ECMO)
• Inability to receive the Geneva cocktail by enteral way
• Severe or terminal Renal impairment (defined as GFR<30ml/min according to Cockroft-Gault)
• Severe chronic hepatic insufficiency (CHILD B-C)
• Sensitivity to any of the drugs used in the Geneva Cocktail
• Intake of drugs altering CYPs activity (Strong inhibitor or inducer based on https://www.hug.ch/sites/hde/files/structures/pharmacologie_et_toxicologie_cliniques/a5_cytochromes_6_2.pdf)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Evaluate the impact of temporary mechanical circulatory support on the activity of CYPs as measured with metabolic ratios MRs (CYP activity at D3 post tMCS implantation and 14 days after tMCS explantation vs the activity of CYPs in the control grou	During the ECMO	CYP450 3A4, 2C19, 2D6, 2B6, 1A2 activity will be assessed in using the metabolic ratio of the following probe respectively: midazolam, esomeprazole, dextrometorphan, bupropion and caffein.

Secondary Outcome Measures

Name	Time	Method
Evaluate the correlation between the activity of CYPs and IL-6 levels	During the ECMO
Evaluate the correlation between the activity of CYPs (MRs) and CRP levels	During the ECMO
Evaluate the correlation between the activity of CYPs (MRs) and TNF-α levels	During the ECMO
Evaluate the correlation between the activity of CYPs (MRs) and IL-1β levels	During the ECMO
Evaluate the correlation between the activity of CYPs (MRs) and IFN-γ levels	During the ECMO
Compare CYP activity vs expected CYP activity based on patients' CYP genotyping	During the ECMO	CYP phenotyping based classification in metabolizer status (UM, NM, IM or PM) using metabolic ratios will be compared to genotyping based classification from the star allele nomenclature according to Pharmacogene Variation (PharmVar) Consortium. ).
Compare CYP activity based on phenotyping between VA-EMCO and micro-axial pump device (Impella® CP)	During the ECMO	CYP450 CYP3A4, 2C19, 2D6, 2C19, 1A2 activity will be determined as mentionned for the primary issue and will be compared between the groups VA-ECMO and micro-axial pump device

Trial Locations

Locations (1)

University Hospital Of Geneva; 🇨🇭 Geneva, Switzerland