Clearance of Vasoactive Metabolites With Blood Purification

NCT06109142 | Recruiting

• 2 other identifiers: APHP2300012022-A01439-34
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Critically Ill Patients

Keywords

Intensive care; Septic shock; Inflammatory mediators; Renin Angiotensin System

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Evolution of the vaso-inotropic score within 72 hours of management

  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).

  Baseline - 24 hours - 72 hours

• Clearance of endothelial permeability markers (soluble E-selectin, thromboxane A2, endothelium-derived relaxing factor, bradykinin).

  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).

  Baseline - 24 hours - 72 hours

• Mortality at 90 days

  Baseline - 24 hours - 90 days

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

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).

You may qualify if:

• 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

You may not qualify if:

• No need for hemofiltration.
• Citrate anticoagulation of the hemofiltration circuit
• Patient under judicial protection and adults under guardianship or curatorship.
• Patient with no social security affiliation

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (3)

Garches hospital

Garches, 92380, France

NOT YET RECRUITING

Bicetre hospital

Le Kremlin-Bicêtre, 94250, France

RECRUITING

Hôpital Paul Brousse

Villejuif, 94800, France

NOT YET RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood - Plasma

MeSH Terms

Conditions

Shock, Septic

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• Pierre Tissieres

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pierre Tissieres

CONTACT

0145213205; pierre.tissieres@aphp.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2023
• First Posted: October 31, 2023
• Study Start: July 11, 2024
• Primary Completion: March 11, 2026
• Study Completion (Estimated): June 11, 2026
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)