Clinical trial NCT06662084: The ECMOCYP (cytochromes P450 Activity) Study
Official title: Impact of Temporary Mechanical Circulatory Support (tMCS) on Cytochromes P450 Activity Measured with Dried Blood Spot
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: ECMO
Cardiogenic Shock
Temporary Mechanical Circulatory Support
Keywords: ecmo
cardiogenic shock
Temporary Mechanical Circulatory Support
TMCS
CYP450
phenotyping
genotyping
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
Collaborators: name: Jean Terrier
name: Benjamin Assouline
name: Raphël Giraud
name: Karim Bendjelid
name: Caroline Samer
name: Youssef Daali
name: Anastasia Zaslavskaya
First posted: 2024-10-28
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: * 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) Hospitalised in intensive care unit

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)

Eligibility criteria: 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)

Primary outcomes:
measure: 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
timeFrame: During the ECMO
Secondary outcomes:
measure: Evaluate the correlation between the activity of CYPs and IL-6 levels
timeFrame: During the ECMO
measure: Evaluate the correlation between the activity of CYPs (MRs) and CRP levels
timeFrame: During the ECMO
measure: Evaluate the correlation between the activity of CYPs (MRs) and TNF-α levels
timeFrame: During the ECMO
measure: Evaluate the correlation between the activity of CYPs (MRs) and IL-1β levels
timeFrame: During the ECMO
measure: Evaluate the correlation between the activity of CYPs (MRs) and IFN-γ levels
timeFrame: During the ECMO
measure: Compare CYP activity vs expected CYP activity based on patients' CYP genotyping
timeFrame: During the ECMO
measure: Compare CYP activity based on phenotyping between VA-EMCO and micro-axial pump device (Impella® CP)
timeFrame: During the ECMO
Other outcomes:
Locations:
city: Geneva
country: Switzerland
facility: University Hospital Of Geneva
Study officials:
References: