Immunothrombosis With Septic Shock Undergoing Renal Replacement Therapy With the OXIRIS Membrane

Sepsis Clinical Trial

— PLAQSIRIS  

Official title:

Investigation of Immunothrombosis in Intensive Care Patients With Septic Shock Undergoing Renal Replacement Therapy With the OXIRIS Membrane

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06440317
• Other study ID #: CHUBX 2023/93
• Status: Not yet recruiting
• Start date: June 2024
• Est. completion date: July 2025

Study information

• Verified date: May 2024
• Source: University Hospital, Bordeaux
• Contact: Antoine DEWITTE, Dr
• Phone: 05 57 65 68 66
• Email: antoine.dewitte[@]u-bordeaux.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Sepsis remains a global scourge. Before the SARS-CoV-2 pandemic, the World Health Organization estimated approximately 49 million cases annually, resulting in 11 million deaths. Defined by dysregulated host response to infection, sepsis leads to vital organ failure. Renal dysfunction affects about half of ICU patients, necessitating extracorporeal renal replacement therapy in approximately 10% of cases, alongside coagulation system involvement typified by thrombocytopenia. Immunothrombotic phenomena are pivotal in sepsis pathophysiology, activating coagulation and disrupting immune responses. Microcirculatory impairment, mediated by neutrophils, monocytes, and platelets, worsens vital organ perfusion. Excessive production of Neutrophil Extracellular Traps (NETs) is implicated in microcirculatory compromise during sepsis.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: July 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients aged 18 years and older
• Admitted to the intensive care unit with septic shock, defined as an increase in the Sequential Organ Failure Assessment (SOFA) score of at least 2 points due to infection, requiring vasopressor drugs to maintain a mean arterial pressure (MAP) = 65 mmHg, and a lactate level > 2 mmol/L (18 mg/dL) despite adequate fluid resuscitation
• Requiring renal replacement therapy according to consensus indications:
• KDIGO stage 3 acute kidney injury with oliguria or anuria persisting for more than 72 hours
• Urea > 40 mmol/L
• Plasma potassium > 5.5 mmol/L despite medical treatment
• pH < 7.15 (pure metabolic acidosis with PaCO2 < 30 mmHg or mixed acidosis with PaCO2 > 50 mmHg without the possibility of improving alveolar ventilation)
• Acute pulmonary edema secondary to hydrosaline overload resulting in severe hypoxemia (oxygen flow > 5 L/min or FiO2 > 50% during mechanical ventilation to maintain SaO2 > 95%) despite diuretic therapy
• Receiving continuous renal replacement therapy with a high-adsorption membrane (oXiris membrane) or a conventional membrane (HF1400 membrane)

Exclusion Criteria:

• Known history of constitutional thrombopathy (Bernard Soulier disease, Glanzmann thrombasthenia, Gray's syndrome or dense granule disease)
• Myelodysplastic or myeloproliferative syndrome
• Autoimmune thrombocytopenic purpura
• Acute leukemia
• Hemorrhagic shock
• Platelet transfusion within 7 days prior to inclusion
• Antiplatelet therapy with clopidogrel or ticagrelor within 5 days prior to inclusion, prasugrel or dipyridamole within 7 days prior to inclusion
• Active HIV infection or hepatitis B or C
• Pregnant woman
• Not affiliated to a social security system or not benefiting from such a system

Related Conditions & MeSH terms

• Sepsis

Intervention

Device:
• Hemofiltration membranes (the oXiris membrane® and the HF1400® membrane)
The PRISMAFLEX® or PRISMAX® control unit (pre- and post-dilution with a prescribed treatment dose > 25 ml/kg/h) with regional citrate anticoagulation and a substitution solution by PHOXILLUM will be used regardless of the type of membrane used (the oXiris membrane and the HF 1400 membrane), also as part of routine care provided in the ICU.

Locations

Country	Name	City	State
France	Hopital Haut-Lévêque	Pessac

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Bordeaux	Baxter Healthcare Corporation

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immunothrombosis : Concentration of platelet activation markers	Dosages of platelet activation markers, before and after the renal replacement therapy membrane : oXiris membrane or conventional membrane	12 months after inclusion day
Secondary	NETosis : Concentration of Neutrophil Extracellular Traps	Dosages of Neutrophil Extracellular Traps, before and after the renal replacement therapy membrane : oXiris membrane or conventional membrane	12 months after inclusion day
Secondary	Monocyte activation : Concentration of monocyte (CD14+)	Dosages of monocyte (CD14+), before and after the renal replacement therapy membrane : oXiris membrane or conventional membrane	12 months after inclusion day