Impact of Temporary Mechanical Circulatory Support (tMCS) on Cytochromes P450 Activity Measured with Dried Blood Spot
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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).
详细描述
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)
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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)
结局指标
主要结局
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
时间窗: 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.
次要结局
- 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)
- Compare CYP activity based on phenotyping between VA-EMCO and micro-axial pump device (Impella® CP)(During the ECMO)
研究者
Jean Terrier
MD, PharmD, PhD
University Hospital, Geneva