The ECMOCYP (cytochromes P450 Activity) Study

Официальное название

Impact of Temporary Mechanical Circulatory Support (tMCS) on Cytochromes P450 Activity Measured with Dried Blood Spot

Обзор

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).

Подробное описание

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)

Вмешательства

• Диагностический тест phenotype
  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

Первичные конечные точки

• 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 [Срок оценки: During the ECMO]

Вторичные конечные точки (7)

• Evaluate the correlation between the activity of CYPs and IL-6 levels [Срок оценки: During the ECMO]
• Evaluate the correlation between the activity of CYPs (MRs) and CRP levels [Срок оценки: During the ECMO]
• Evaluate the correlation between the activity of CYPs (MRs) and TNF-α levels [Срок оценки: During the ECMO]
• Evaluate the correlation between the activity of CYPs (MRs) and IL-1β levels [Срок оценки: During the ECMO]
• Evaluate the correlation between the activity of CYPs (MRs) and IFN-γ levels [Срок оценки: During the ECMO]
• Compare CYP activity vs expected CYP activity based on patients' CYP genotyping [Срок оценки: During the ECMO]
• Compare CYP activity based on phenotyping between VA-EMCO and micro-axial pump device (Impella® CP) [Срок оценки: During the ECMO]

Критерии участия

Критерии включения

• 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).

Критерии исключения

• 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)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

Швейцария · 1 центр

• University Hospital Of Geneva — Geneva

Идентификаторы

NCT: NCT06662084 · 2023-01398

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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