The ECMOCYP (cytochromes P450 Activity) Study

NCT06662084 | Recruiting

• 1 other identifier: 2023-01398
• Study Type: observational
• Target: 46
• Locations: 1 country
• Sites: 1

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).

Conditions

ECMO; Cardiogenic Shock; Temporary Mechanical Circulatory Support

Keywords

ecmo; cardiogenic shock; Temporary Mechanical Circulatory Support; TMCS; CYP450; phenotyping; genotyping

Outcome Measures

Primary Outcomes (1)

• 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

  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.

  During the ECMO

Secondary Outcomes (7)

• 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

Study Arms (2)

Temporary mechanical circulatory support group

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).

Diagnostic Test: phenotype

Control group

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)

Diagnostic Test: phenotype

Interventions

phenotype DIAGNOSTIC_TEST

Eligible patients will receive orally the cocktail probe drugs ( via a naso-gastric tube at D3 after tMCS implantation or after the beginning of the cardiogenic shock for the control group) and via an oral administration at 14 days after tMCS explantation (or cardiogenic shock termination for the control group defined as: no need to use inortropic or vasopressive agent and absence of organ insufficiency). The phenotyping probe drugs of the Geneva Cocktail will be given as: one capsule containing the remaining probe 'cocktail' drugs. According to clinical experience in our intensive care unit department, inflammation related to tMCS peaks at D3 after tMCS implantation. Blood samples will be collected from the central venous line 2 hours after drug administration for CYP phenotyping and genotyping. Inflammatory markers blood levels (Il-6, TNF-α, Il-1β, IFN-γ) will be measured at tMCS implantation or shock initiation and at the same time than CYP phenotyping.

Also known as: CRP, IL-6, TNF-alpha, IL-1β, IFN-γ

Control group; Temporary mechanical circulatory support group

Eligibility Criteria

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

You may qualify if:

• 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).

You may not qualify if:

• 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)

Sponsors & Collaborators

• University Hospital, Geneva: lead
• Jean Terrier: collaborator
• Benjamin Assouline: collaborator
• Raphël Giraud: collaborator
• Karim Bendjelid: collaborator
• Caroline Samer: collaborator
• Youssef Daali: collaborator
• Anastasia Zaslavskaya: collaborator

Study Sites (1)

University Hospital Of Geneva

Geneva, 1205, Switzerland

RECRUITING

MeSH Terms

Conditions

Shock, Cardiogenic

Interventions

Phenotype

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Genetic Phenomena

Central Study Contacts

Jean Terrier, Dr

CONTACT

+41795530888; jean.terrier@hug.ch

Anastasia Zaslavskaya, Dr

CONTACT

+41795535729; anastasia.zaslavskaya@hug.ch

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PharmD, PhD

Study Record Dates

• First Submitted: September 13, 2024
• First Posted: October 28, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: October 28, 2024

Record last verified: 2024-10

Locations

CH (1)