Clinical trial NCT05079009: Effects of Blood Pulsatility on Von Willebrand Factor During ECCO2R
Official title: Effects of Blood Pulsatility on Von Willebrand Factor During Extracorporeal CO2 Removal (ECCO2R)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Extracorporeal CO2 Removal
Acute Respiratory Distress Syndrome
Chronic Obstructive Pulmonary Disease Exacerbation
Pulmonary Disease
Keywords: ECCO2R
Willebrand factor
ARDS
COPD
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Xenios AG
First posted: 2021-10-15
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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").

Eligibility criteria: 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

Primary outcomes:
measure: Level course of Willebrand Factor high molecular weight multimers in plasma
timeFrame: Up to 30 days
Secondary outcomes:
measure: Rate of specific adverse events
timeFrame: Up to 30 days
measure: Level of von Willebrand factor
timeFrame: Up to 30 days
measure: Level of P-Selectin
timeFrame: Up to 30 days
measure: Level of leucoplatelet aggregates
timeFrame: Up to 30 days
measure: Level of proplatelet aggregates
timeFrame: Up to 30 days
measure: Level of platelet
timeFrame: Up to 30 days
measure: Level of microparticles
timeFrame: Up to 30 days
measure: Level of leucocytes
timeFrame: Up to 30 days
measure: Level of endothelial cells
timeFrame: Up to 30 days
measure: Level of NETs (Neutrophil Extracellular Traps)
timeFrame: Up to 30 days
measure: Level of free DNA
timeFrame: Up to 30 days
measure: Level of Nucleosome
timeFrame: Up to 30 days
measure: Level of FiO2
timeFrame: Up to 29 days
measure: VT (Tidal Volume)
timeFrame: Up to 29 days
measure: Respiratory rate
timeFrame: Up to 29 days
measure: Level of PaO2
timeFrame: Up to 29 days
measure: Level of PaCO2
timeFrame: Up to 29 days
measure: pH
timeFrame: Up to 29 days
measure: Level of SaO2
timeFrame: Up to 29 days
measure: Heart rate
timeFrame: Up to 30 days
measure: Respiratory rate
timeFrame: Up to 30 days
measure: Blood Pressure
timeFrame: Up to 30 days
measure: Pump speed
timeFrame: Up to 29 days
measure: Pulsatility setting
timeFrame: Up to 29 days
measure: Extracorporal blood flow
timeFrame: Up to 29 days
measure: Extracorporal pressures
timeFrame: Up to 29 days
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital européen Georges Pompidou
Study officials:
affiliation: AP-HP, Hôpital Européen Georges Pompidou, Paris
name: Jean-Luc Diehl, PhD
role: STUDY_CHAIR
References:
citation: Kalbhenn J, Neuffer N, Zieger B, Schmutz A. Is Extracorporeal CO2 Removal Really "Safe" and "Less" Invasive? Observation of Blood Injury and Coagulation Impairment during ECCO2R. ASAIO J. 2017 Sep/Oct;63(5):666-671. doi: 10.1097/MAT.0000000000000544.