Clinical trial NCT06440317: Immunothrombosis With Septic Shock Undergoing Renal Replacement Therapy With the OXIRIS Membrane
Official title: Investigation of Immunothrombosis in Intensive Care Patients With Septic Shock Undergoing Renal Replacement Therapy With the OXIRIS Membrane
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Sepsis
Keywords: Intensive Care
Immunothrombosis
NETs
Neutrophils
Platelets
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
Collaborators: name: Baxter Healthcare Corporation
First posted: 2024-06-03
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Eligible patients for this study will undergo renal replacement therapy using two hemofiltration membranes commonly used in intensive care units

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Immunothrombosis : Concentration of platelet activation markers
timeFrame: 12 months after inclusion day
Secondary outcomes:
measure: NETosis : Concentration of Neutrophil Extracellular Traps
timeFrame: 12 months after inclusion day
measure: Monocyte activation : Concentration of monocyte (CD14+)
timeFrame: 12 months after inclusion day
Other outcomes:
Locations:
city: Pessac
country: France
facility: Hopital Haut-Lévêque
Study officials:
affiliation: ImmunoConcEpT, Bordeaux University
name: Maria MAMANI, Pr
role: STUDY_CHAIR
References: