Effects of Blood Pulsatility on Von Willebrand Factor During ECCO2R

Study Overview
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Brief Summary
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The primary objective of the study is to demonstrate that the ECCO2R pulsatile configuration prevents the Willebrand factor high molecular weight multimers decrease observed under continuous blood flow configurations. The secondary objectives are to quantify the CO2 extracorporeal removal in the pulsatile configuration, to describe complications (hemorrhagic, thrombotic and hemolytic), to describe patients' gas exchanges under ECCO2R, to describe the clinical course of the patients under ECCO2R as well as during the whole stay in the Intensive Care Unit (ICU).

Detailed Description
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A track of major interest to prevent bleeding complications in ECCO2R, and more generally in extracorporeal circulations, is to prevent acquired Willebrand disease. Indeed, a loss of Willebrand factor high molecular weight multimers (Whmwm) is frequently observed in conditions characterized by a continuous blood flow, associated with a high incidence of bleeding. A publication suggested the existence of this phenomenon under ECCO2R achieved through the medical device Hemolung (Alung technology, USA). We preliminary observed an almost constant and early (< 24 hours) decrease in Willebrand factor high molecular weight multimers under ECCO2R. Such a phenomenon is considered as a major factor of hemorrhagic complications. We hypothesize that use of pulsatile extracorporeal blood flow configuration during the full length of ECCO2R therapy, as authorized by the Xenios console (Xenios AG, Heilbronn), would preserve a normal value of Whmwm, mainly by changing the conditions of shear constraints (shear stress).

Official Title
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Effects of Blood Pulsatility on Von Willebrand Factor During Extracorporeal CO2 Removal (ECCO2R)

Conditions
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Extracorporeal CO2 Removal, Acute Respiratory Distress Syndrome, Chronic Obstructive Pulmonary Disease Exacerbation, Pulmonary Disease

Intervention / Treatment
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* Device: ECCO2R pulsatile configuration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patient hospitalized in the Georges Pompidou European Hospital medical ICU Patient with or without SARS-CoV-2 infection ECCO2R treatment decision made by the medical team (regardless of the FLOW-ECCO2R protocol): mainly ECCO2R to enable ultraprotective ventilation for Acute respiratory distress syndrome (ARDS) patients or to avoid intubation or to shorten invasive mechanical ventilation in Chronic obstructive pulmonary disease (COPD) patients Affiliation to a social security regimen Informed consent (patient, trusted person, close family) , by default emergency inclusion notified in medical file and pursuance consent sought Negative serum or urinary β-hCG for women of child-bearing potential Exclusion Criteria: Known allergy to heparin or to any of the excipients of the specialty used History of type II heparin-induced thrombopenia Thrombocytopenia (platelet < 100.000/mm3) Constitutional hemostasis disease interfering with biological assays Organic lesion likely to bleed Bleeding manifestations or tendencies linked to disorders of hemostasis Intracerebral hemorrhage Participation in another interventional research involving human participants Pregnant or breastfeeding women Protected adults (including individual under guardianship by court order) Persons deprived of their liberty by judicial or administrative decision

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ECCO2R pulsatile configuration<br>Adult patients hospitalized in the medical ICU for whom a treatment by ECCO2R has been indicated. | Device: ECCO2R pulsatile configuration<br>* Use of the pulsatile extracorporeal blood flow configuration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level course of Willebrand Factor high molecular weight multimers in plasma | Quantification of plasma Willebrand Factor high molecular weight multimers by the Hydrasys system | Up to 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of specific adverse events | To describe the complications under ECCO2R: hemorrhagic, thrombotic and hemolytic adverse events | Up to 30 days | 
| Level of von Willebrand factor | To quantify von Willebrand activity/antigenemy | Up to 30 days | 
| Level of P-Selectin | Characterization of the blood coagulation system | Up to 30 days | 
| Level of leucoplatelet aggregates | Characterization of the blood coagulation system | Up to 30 days | 
| Level of proplatelet aggregates | Characterization of the blood coagulation system | Up to 30 days | 
| Level of platelet | Characterization of the blood coagulation system | Up to 30 days | 
| Level of microparticles | Characterization of the blood coagulation system | Up to 30 days | 
| Level of leucocytes | Characterization of the blood coagulation system | Up to 30 days | 
| Level of endothelial cells | Characterization of the blood coagulation system | Up to 30 days | 
| Level of NETs (Neutrophil Extracellular Traps) | Characterization of the blood coagulation system | Up to 30 days | 
| Level of free DNA | Characterization of the blood coagulation system | Up to 30 days | 
| Level of Nucleosome | Characterization of the blood coagulation system | Up to 30 days | 
| Level of FiO2 | Recording of mechanical ventilator parameters (Non-Invasive Ventilation or Invasive Mechanical Ventilation) to describe the patients' clinical course under ECCO2R as well as during the whole stay in the ICU.v | Up to 29 days | 
| VT (Tidal Volume) | Recording of mechanical ventilator parameters (Non-Invasive Ventilation or Invasive Mechanical Ventilation) to describe the patients' clinical course under ECCO2R as well as during the whole stay in the ICU.v | Up to 29 days | 
| Respiratory rate | Recording of mechanical ventilator parameters (Non-Invasive Ventilation or Invasive Mechanical Ventilation) to describe the patients' clinical course under ECCO2R as well as during the whole stay in the ICU.v | Up to 29 days | 
| Level of PaO2 | Description of the arterial blood gas parameters under ECCO2R | Up to 29 days | 
| Level of PaCO2 | Description of the arterial blood gas parameters under ECCO2R | Up to 29 days | 
| pH | Description of the arterial blood gas parameters under ECCO2R | Up to 29 days | 
| Level of SaO2 | Description of the arterial blood gas parameters under ECCO2R | Up to 29 days | 
| Heart rate | To describe the patient vital parameters under ECCO2R | Up to 30 days | 
| Respiratory rate | To describe the patient vital parameters under ECCO2R | Up to 30 days | 
| Blood Pressure | To describe the patient vital parameters under ECCO2R | Up to 30 days | 
| Pump speed | Description of the ECCO2R parameters | Up to 29 days | 
| Pulsatility setting | Description of the ECCO2R parameters | Up to 29 days | 
| Extracorporal blood flow | Description of the ECCO2R parameters | Up to 29 days | 
| Extracorporal pressures | Description of the ECCO2R parameters | Up to 29 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ECCO2R, Willebrand factor, ARDS, COPD