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| Name | Class |
|---|---|
| Jean Terrier | UNKNOWN |
| Benjamin Assouline | UNKNOWN |
| Raphël Giraud | UNKNOWN |
| Karim Bendjelid |
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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).
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:
Secondary endpoints:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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). |
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| 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) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jean Terrier, Dr | Contact | +41795530888 | jean.terrier@hug.ch | |
| Anastasia Zaslavskaya, Dr | Contact | +41795535729 | anastasia.zaslavskaya@hug.ch |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Of Geneva | Recruiting | Geneva | 1205 | Switzerland |
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| ID | Term |
|---|---|
| D012770 | Shock, Cardiogenic |
| ID | Term |
|---|---|
| D009203 | Myocardial Infarction |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D010641 | Phenotype |
| ID | Term |
|---|---|
| D055614 | Genetic Phenomena |
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| Caroline Samer | UNKNOWN |
| Youssef Daali | UNKNOWN |
| Anastasia Zaslavskaya | UNKNOWN |
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|
| 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 | 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. ). | During the ECMO |
| Compare CYP activity based on phenotyping between VA-EMCO and micro-axial pump device (Impella® CP) | 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 | During the ECMO |
| D014652 |
| Vascular Diseases |
| D007238 | Infarction |
| D007511 | Ischemia |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009336 | Necrosis |
| D012769 | Shock |