Clearance of Vasoactive Metabolites With Blood Purification

Critically Ill Patients Clinical Trial

— VITAL  

Official title:

Pilot Study on the Effect of Oxiris Haemofiltration Membrane on Haemodynamic Stabilisation and Clearance of Vasoactive Metabolites

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06109142
• Other study ID #: APHP230001
• Secondary ID: 2022-A01439-34
• Status: Not yet recruiting
• Start date: April 1, 2024
• Est. completion date: March 1, 2026

Study information

• Verified date: November 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Pierre Tissieres
• Phone: 01 45 21 32 05
• Email: pierre.tissieres[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: March 1, 2026
• Est. primary completion date: December 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Critical Illness
• Critically Ill Patients

Locations

Country	Name	City	State
France	Garches hospital	Garches
France	Bicetre hospital	Le Kremlin Bicetre

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	50% reduction in vasoinotropic score within 24 hours of initiation on oXiris.	Vaso-inotropic score calculated at baseline and H24. (Minimum 0 = better outcome)	Baseline - 24 hours
Secondary	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)	Baseline - 3 hours - 6 hours - 12 hours - 24 hours - 48 hours - 72 hours
Secondary	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	Baseline - 24 hours - 72 hours
Secondary	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	Baseline - 24 hours - 72 hours
Secondary	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	Baseline - 24 hours - 72 hours
Secondary	Mortality at 90 days	the correlation between concentrations of metabolites of angiotensin and 90-day mortality	Baseline - 24 hours - 90 days
Secondary	haemodynamic response (concentrations of metabolites of angiotensin) at 24 hours of treatment with oXiris.	the concentrations of metabolites of angiotensin	Baseline - 24 hours - 90 days