Critically Ill PatientsVITALNCT06109142
Clearance of Vasoactive Metabolites With Blood Purification
An observational study of Critically Ill Patients, run by Assistance Publique - Hôpitaux de Paris at 3 sites in France.
Trial summary
Extracorporeal blood purification is a supportive therapy in the management of patients with sepsis or vasoplegic shock. The pathophysiology of sepsis is based on an inappropriate host response to infection. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Critically Ill Patients
- How many people
- 30 participants
- Where
- 3 sitesFrance
- Study dates
- 11 Jul 2024to 11 Jun 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
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 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: The target population for pediatric resuscitation concerns: * Patients in septic shock requiring extra-renal purification, i.e. 10-20 patients/year * Perioperative liver transplant patients, 20% of whom require extra-renal purification for multi-visceral failure associated with shock vasoplegic (5-10 patients/year) For adult resuscitations: * Patients in septic shock requiring extra-renal purification, i.e. 10-20% of these patients (30 patients per center per year for 2 centers) * Perioperative patients of major abdominal surgery with multi-organ renal failure requiring extra-renal purification (20 patients per year for a center).
Who may be able to join
- Patients admitted to intensive care with vasoplegic shock (hemodynamic support by noradrenaline).
- Adult or child ≥ 6 years and 30kg
- Indication for extrarenal purification for acute, chronic renal failure, oliguric hydrosodic overload, refractory metabolic acidosis or severe hydroelectrolyte disorder
- Clinician's decision to use an oXiris hemofilter with blood purification capability
- For adult patients: no opposition from the patient (or person of trust or close friend if the patient is unable to be informed)
- For minor patients: no opposition of the holders of parental authority
Who cannot join
- No need for hemofiltration.
- Citrate anticoagulation of the hemofiltration circuit
- Inclusion in a category 1 or 2 interventional study protocol. Patients included in category 3 interventional research will be able to participate in the study after assessment by the physician.
- Patient under judicial protection and adults under guardianship or curatorship.
- Patient with no social security affiliation
Trial locations and contacts
3 sites in 1 country.
France3 sites, 3 recruiting
- Not yet recruiting
Garches hospital
Garches, 92380
Djillali ANNANE, djillali.annane@aphp.fr
Djillali ANNANE
- Recruiting
Bicetre hospital
Le Kremlin-Bicêtre, 94250
Pierre Tissieres, 01 45 21 32 05, pierre.tissieres@aphp.fr
Luc MORIN
- Not yet recruiting
Hôpital Paul Brousse
Villejuif, 94800
Faouzi SALIBA, 01.45.59.64.12, faouzi.saliba@aphp.fr
Faouzi SALIBA
About this study
Official title: Pilot Study on the Effect of Oxiris Haemofiltration Membrane on Haemodynamic Stabilisation and Clearance of Vasoactive Metabolites
Extracorporeal blood purification is a supportive therapy in the management of patients with sepsis or vasoplegic shock. The pathophysiology of sepsis is based on an inappropriate host response to infection. Certain medical devices with higher adsorption capacity make it possible to limit this inappropriate response and could thus improve the hemodynamics of patients in septic or vasoplegic shock. The preliminary experience of the investigators from clinical data of vasopressor withdrawal in pediatric patients treated with oXiris shows a 50% reduction in the vasopressor score, Vaso Inotropic Score (VIS), for 40% of patients within 24 hours following the start of treatment. Similar results were found in adult patients treated for severe COVID-19 or vasoplegic shock by the other centers participating in the study.
Cytokine purification is an important physiological effect of purification membranes. However, this may not fully explain the rapid hemodynamic improvement of patients treated with an oXiris membrane.
Read more
The role of angiotensin metabolites (Ang 1-5, 1-7, 1-9) in the systemic vascular tone of patients has been recently discussed. The administration of angiotensin 2 in vasoplegic shock in adults helps correct hypotension. In the group of patients with increased renin, this treatment was associated with a reduction in mortality. Indeed, increased renin associated with dysfunction of Angiotensin Converting Enzyme (ACE) leads to an accumulation of Angiotensin 1 which degrades to Ang 1-7.
The hypothesis f the investigators is that the concentration of Ang 1 and Ang 1-7 is elevated in cases of vasoplegic shock and that the clearance of these vasodilator peptides by blood purification is associated with clinical improvement.
Read the detailed description
This is a pilot study, non-interventional research involving the human subjects, category 3, aimed at measuring the clinical and biological the clinical and biological effects of using the oXiris hemofiltration hemofiltration membrane.
As part of the treatment: oXiris membrane hemofiltration with Prismaflex system, Phoxylium or Hémosol B0 dialysis solution, upper or lower dialysis catheter. Anticoagulation with heparin, citrate or none in case of severe haemostasis disorders. Treatment volume of 35 ml/kg/h maximum.
For research purposes: collection of additional blood tubes (2 x 5mL heparinized tube) added to the usual samples, at the following times:
Baseline (before starting treatment), under hemofiltration at 24h +/- 6h of treatment and at 72 hours +/- 12 hours.
These samples will be analyzed by liquid chromatography - mass spectrometry / mass spectrometry (LC-MS/MS) by Attoquant diagnostics®, a laboratory specialized in analyses of the Renin-Angiotensin system. The angiotensins assayed are Angiotensin I, II, III and IV, as well as the intermediate peptides (1-5, 1-7, 1-9, 2-10, 2-7 and 3-7) and regulatory enzymes (renin, angiotensin converting enzyme, angiotensin 2-converting enzyme and neprilysin).
Angiotensin metabolites have a very short half-life. Their depends on enzyme activity and degradation by circulating proteases. Two techniques are used to determine circulating concentration rapid treatment with protease inhibitors or the equilibrium technique.
For the equilibrium technique, samples are incubated again to restore metabolite concentration prior to analysis. The samples at 3 time points (Baseline, H24 and H72) are analyzed using the equilibrium. The H24 sample will also be analyzed with a protease inhibitor pre-treatment.
Patients will be monitored for 3 months (90-day mortality) using data collected collected in the course of care.
Data from medical records and biological analyses will be entered into an eCRF. Data management will be carried out throughout the study, to enable baseline freezing and statistical analysis as early as possible after the end of the last patient's follow-up.
- Conditions
- Critically Ill Patients
- Keywords
- Intensive care, Septic shock, Inflammatory mediators, Renin Angiotensin System
- Medical subject headings
- Shock, Septic
What is being measured
The primary outcome is the main question the study is designed to answer.
50% reduction in vasoinotropic score within 24 hours of initiation on oXiris.
Vaso-inotropic score calculated at baseline and H24. (Minimum 0 = better outcome)
Measured: Baseline - 24 hours
Secondary outcomes (6)
Evolution of the vaso-inotropic score within 72 hours of management
Vaso-inotropic score calculated at baseline - 3 hours - 6 hours - 12 hours - 24 hours - 48 hours - 72 hours (Minimum 0 = better outcome)
Measured: Baseline - 3 hours - 6 hours - 12 hours - 24 hours - 48 hours - 72 hours
Quantitative determination of angiotensins (Ang I, II, III, IV, 1-5, 1-7, 1-9, 2-7, 2-10 and 3-7) and regulatory enzymes (renin, angiotensin-converting enzyme, angiotensin-converting enzyme 2 and neprilysin).
Dosage of angiotensins (Ang I, II, III, IV, 1-5, 1-7, 1-9, 2-7, 2-10 and 3-7) and regulatory enzymes (renin, angiotensin-converting enzyme, angiotensin-converting enzyme 2 and neprilysin) by LC/MS
Measured: Baseline - 24 hours - 72 hours
Clearance of endothelial permeability markers (soluble E-selectin, thromboxane A2, endothelium-derived relaxing factor, bradykinin).
Dosage of Clearance of endothelial permeability markers (soluble E-selectin, thromboxane A2, endothelium-derived relaxing factor, bradykinin) by RT-PCR
Measured: Baseline - 24 hours - 72 hours
Markers of sepsis-induced immunosuppression expressed by HLA-DR monocytes in flow cytometry and selected cytokines (IL-1 beta, IL-6, IL-8, IL-10, TNF-alpha).
Identification of Markers of sepsis-induced immunosuppression expressed by HLA-DR monocytes in flow cytometry and selected cytokines (IL-1 beta, IL-6, IL-8, IL-10, TNF-alpha) by flow cytometry
Measured: Baseline - 24 hours - 72 hours
Mortality at 90 days
the correlation between concentrations of metabolites of angiotensin and 90-day mortality
Measured: Baseline - 24 hours - 90 days
haemodynamic response (concentrations of metabolites of angiotensin) at 24 hours of treatment with oXiris.
the concentrations of metabolites of angiotensin
Measured: Baseline - 24 hours - 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2023
- Study start11 Jul 2024
- Primary completion11 Mar 2026 (estimated)
- Study completion11 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Critically Ill PatientsStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pierre Tissieres, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06109142
- Sponsor's protocol ID
- APHP230001
- Other IDs
- 2022-A01439-34
- Acronym
- VITAL
- Status last verified
- Sep 2024
- First submitted
- 2 Oct 2023
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study on the Effect of Oxiris Haemofiltration Membrane on Haemodynamic Stabilisation and Clearance of Vasoactive Metabolites
- ClinicalTrials.gov ID
- NCT06109142
- Acronym / sponsor ID
- VITAL / APHP230001
- Conditions
- Critically Ill Patients
- Keywords
- Intensive care, Septic shock, Inflammatory mediators, Renin Angiotensin System
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 11 Jul 2024 (actual)
- Primary completion
- 11 Mar 2026 (estimated)
- Study completion
- 11 Jun 2026 (estimated)
- First posted
- 31 Oct 2023 (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.
Extracorporeal blood purification is a supportive therapy in the management of patients with sepsis or vasoplegic shock. The pathophysiology of sepsis is based on an inappropriate host response to infection. Certain medical devices with higher adsorption capacity make it possible to limit this inappropriate response and could thus improve the hemodynamics of patients in septic or vasoplegic shock. The preliminary experience of the investigators from clinical data of vasopressor withdrawal in pediatric patients treated with oXiris shows a 50% reduction in the vasopressor score, Vaso Inotropic Score (VIS), for 40% of patients within 24 hours following the start of treatment. Similar results were found in adult patients treated for severe COVID-19 or vasoplegic shock by the other centers participating in the study.
Cytokine purification is an important physiological effect of purification membranes. However, this may not fully explain the rapid hemodynamic improvement of patients treated with an oXiris membrane.
The role of angiotensin metabolites (Ang 1-5, 1-7, 1-9) in the systemic vascular tone of patients has been recently discussed. The administration of angiotensin 2 in vasoplegic shock in adults helps correct hypotension. In the group of patients with increased renin, this treatment was associated with a reduction in mortality. Indeed, increased renin associated with dysfunction of Angiotensin Converting Enzyme (ACE) leads to an accumulation of Angiotensin 1 which degrades to Ang 1-7.
The hypothesis f the investigators is that the concentration of Ang 1 and Ang 1-7 is elevated in cases of vasoplegic shock and that the clearance of these vasodilator peptides by blood purification is associated with clinical improvement.
Detailed description
This is a pilot study, non-interventional research involving the human subjects, category 3, aimed at measuring the clinical and biological the clinical and biological effects of using the oXiris hemofiltration hemofiltration membrane.
As part of the treatment: oXiris membrane hemofiltration with Prismaflex system, Phoxylium or Hémosol B0 dialysis solution, upper or lower dialysis catheter. Anticoagulation with heparin, citrate or none in case of severe haemostasis disorders. Treatment volume of 35 ml/kg/h maximum.
For research purposes: collection of additional blood tubes (2 x 5mL heparinized tube) added to the usual samples, at the following times:
Baseline (before starting treatment), under hemofiltration at 24h +/- 6h of treatment and at 72 hours +/- 12 hours.
These samples will be analyzed by liquid chromatography - mass spectrometry / mass spectrometry (LC-MS/MS) by Attoquant diagnostics®, a laboratory specialized in analyses of the Renin-Angiotensin system. The angiotensins assayed are Angiotensin I, II, III and IV, as well as the intermediate peptides (1-5, 1-7, 1-9, 2-10, 2-7 and 3-7) and regulatory enzymes (renin, angiotensin converting enzyme, angiotensin 2-converting enzyme and neprilysin).
Angiotensin metabolites have a very short half-life. Their depends on enzyme activity and degradation by circulating proteases. Two techniques are used to determine circulating concentration rapid treatment with protease inhibitors or the equilibrium technique.
For the equilibrium technique, samples are incubated again to restore metabolite concentration prior to analysis. The samples at 3 time points (Baseline, H24 and H72) are analyzed using the equilibrium. The H24 sample will also be analyzed with a protease inhibitor pre-treatment.
Patients will be monitored for 3 months (90-day mortality) using data collected collected in the course of care.
Data from medical records and biological analyses will be entered into an eCRF. Data management will be carried out throughout the study, to enable baseline freezing and statistical analysis as early as possible after the end of the last patient's follow-up.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- The target population for pediatric resuscitation concerns: * Patients in septic shock requiring extra-renal purification, i.e. 10-20 patients/year * Perioperative liver transplant patients, 20% of whom require extra-renal purification for multi-visceral failure associated with shock vasoplegic (5-10 patients/year) For adult resuscitations: * Patients in septic shock requiring extra-renal purification, i.e. 10-20% of these patients (30 patients per center per year for 2 centers) * Perioperative patients of major abdominal surgery with multi-organ renal failure requiring extra-renal purification (20 patients per year for a center).
Key inclusion criteria (6 listed)
- Patients admitted to intensive care with vasoplegic shock (hemodynamic support by noradrenaline).
- Adult or child ≥ 6 years and 30kg
- Indication for extrarenal purification for acute, chronic renal failure, oliguric hydrosodic overload, refractory metabolic acidosis or severe hydroelectrolyte disorder
- Clinician's decision to use an oXiris hemofilter with blood purification capability
- For adult patients: no opposition from the patient (or person of trust or close friend if the patient is unable to be informed)
Key exclusion criteria (5 listed)
- No need for hemofiltration.
- Citrate anticoagulation of the hemofiltration circuit
- Inclusion in a category 1 or 2 interventional study protocol. Patients included in category 3 interventional research will be able to participate in the study after assessment by the physician.
- Patient under judicial protection and adults under guardianship or curatorship.
- Patient with no social security affiliation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
50% reduction in vasoinotropic score within 24 hours of initiation on oXiris.
Time frame: Baseline - 24 hours
Vaso-inotropic score calculated at baseline and H24. (Minimum 0 = better outcome)
6 secondary outcomes
Evolution of the vaso-inotropic score within 72 hours of management
Time frame: Baseline - 3 hours - 6 hours - 12 hours - 24 hours - 48 hours - 72 hours
Quantitative determination of angiotensins (Ang I, II, III, IV, 1-5, 1-7, 1-9, 2-7, 2-10 and 3-7) and regulatory enzymes (renin, angiotensin-converting enzyme, angiotensin-converting enzyme 2 and neprilysin).
Time frame: Baseline - 24 hours - 72 hours
Clearance of endothelial permeability markers (soluble E-selectin, thromboxane A2, endothelium-derived relaxing factor, bradykinin).
Time frame: Baseline - 24 hours - 72 hours
Markers of sepsis-induced immunosuppression expressed by HLA-DR monocytes in flow cytometry and selected cytokines (IL-1 beta, IL-6, IL-8, IL-10, TNF-alpha).
Time frame: Baseline - 24 hours - 72 hours
Mortality at 90 days
Time frame: Baseline - 24 hours - 90 days
haemodynamic response (concentrations of metabolites of angiotensin) at 24 hours of treatment with oXiris.
Time frame: Baseline - 24 hours - 90 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Pierre Tissieres principal investigator
Assistance Publique - Hôpitaux de Paris
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Critically Ill Patients, run by Assistance Publique - Hôpitaux de Paris at 3 sites in France.
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 6 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Pierre Tissieres (0145213205, pierre.tissieres@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
50% reduction in vasoinotropic score within 24 hours of initiation on oXiris. (time frame: Baseline - 24 hours). 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 19 Sep 2024.