ECMONCT06662084
The ECMOCYP (cytochromes P450 Activity) Study
An observational study of ECMO and Cardiogenic Shock, run by University Hospital, Geneva at 1 site in Switzerland.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ECMO, Cardiogenic Shock, Temporary Mechanical Circulatory Support
- What is being tested?
- phenotype
- Type of treatment
- Pill or oral medicine
- How many people
- 46 participants
- Where
- 1 siteSwitzerland
- Study dates
- Oct 2024to Jul 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Who may be able to join
- 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).
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland1 site, 1 recruiting
- Recruiting
University Hospital Of Geneva
Geneva, 1205
Jean Terrier, MD, +41795530888, jean.terrier@hug.ch
About this study
Official title: Impact of Temporary Mechanical Circulatory Support (tMCS) on Cytochromes P450 Activity Measured with Dried Blood Spot
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).
Read the 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)
- Being tested
- phenotype
- Keywords
- ecmo, cardiogenic shock, Temporary Mechanical Circulatory Support, TMCS, CYP450, phenotyping, genotyping
- Medical subject headings
- Shock, Cardiogenic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
phenotypeDiagnostic test
Also called CRP, IL-6, TNF-alpha, IL-1β
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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) Receives: Diagnostic Test: phenotype |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: During the ECMO
Secondary outcomes (7)
Evaluate the correlation between the activity of CYPs and IL-6 levels
Measured: During the ECMO
Evaluate the correlation between the activity of CYPs (MRs) and CRP levels
Measured: During the ECMO
Evaluate the correlation between the activity of CYPs (MRs) and TNF-α levels
Measured: During the ECMO
Evaluate the correlation between the activity of CYPs (MRs) and IL-1β levels
Measured: During the ECMO
Evaluate the correlation between the activity of CYPs (MRs) and IFN-γ levels
Measured: 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. ).
Measured: 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
Measured: During the ECMO
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2024
- Study startOct 2024 (estimated)
- Primary completionJul 2026 (estimated)
- Study completionJul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ECMOStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 46 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Geneva
- Sponsor type
- University, hospital or other
- Collaborators
- Jean Terrier, Benjamin Assouline, Raphël Giraud, Karim Bendjelid, Caroline Samer, Youssef Daali, Anastasia Zaslavskaya
- Responsible party
- Principal investigator, Jean Terrier, University Hospital, Geneva
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06662084
- Sponsor's protocol ID
- 2023-01398
- Other IDs
- 2023
- Status last verified
- Oct 2024
- First submitted
- 13 Sep 2024
- Last updated
- 28 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Temporary Mechanical Circulatory Support (tMCS) on Cytochromes P450 Activity Measured with Dried Blood Spot
- ClinicalTrials.gov ID
- NCT06662084
- Acronym / sponsor ID
- 2023-01398
- Keywords
- ecmo, cardiogenic shock, Temporary Mechanical Circulatory Support, TMCS, CYP450, phenotyping, genotyping
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 46 participants (estimated)
- Lead sponsor
- University Hospital, GenevaUniversity, hospital or other
- Collaborators
- Jean Terrier, Benjamin Assouline, Raphël Giraud, Karim Bendjelid, Caroline Samer, Youssef Daali, Anastasia Zaslavskaya
- Study start
- Oct 2024 (estimated)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Jul 2026 (estimated)
- First posted
- 28 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Temporary mechanical circulatory support group | – | Diagnostic Test: phenotypeMale 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). |
| Control group | – | Diagnostic Test: phenotypeMale 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (5 listed)
- 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).
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| phenotypeAlso: CRP, IL-6, TNF-alpha, IL-1βEligible 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. | Diagnostic test | Control group, Temporary mechanical circulatory support group |
Primary outcome
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
Time frame: 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.
7 secondary outcomes
Evaluate the correlation between the activity of CYPs and IL-6 levels
Time frame: During the ECMO
Evaluate the correlation between the activity of CYPs (MRs) and CRP levels
Time frame: During the ECMO
Evaluate the correlation between the activity of CYPs (MRs) and TNF-α levels
Time frame: During the ECMO
Evaluate the correlation between the activity of CYPs (MRs) and IL-1β levels
Time frame: During the ECMO
Evaluate the correlation between the activity of CYPs (MRs) and IFN-γ levels
Time frame: During the ECMO
Compare CYP activity vs expected CYP activity based on patients' CYP genotyping
Time frame: During the ECMO
Compare CYP activity based on phenotyping between VA-EMCO and micro-axial pump device (Impella® CP)
Time frame: During the ECMO
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of ECMO and Cardiogenic Shock, run by University Hospital, Geneva at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jean Terrier, Dr (+41795530888, jean.terrier@hug.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: During the ECMO). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2024.