Effects of Blood Pulsatility on Von Willebrand Factor During ECCO2R (FLOW-ECCO2R)

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

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).

Study Overview

• Status: Recruiting
• Conditions: Acute Respiratory Distress Syndrome; Pulmonary Disease; Extracorporeal CO2 Removal; Chronic Obstructive Pulmonary Disease Exacerbation
• Intervention / Treatment: Device: ECCO2R pulsatile configuration

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").

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Cléo Bourgeois; Phone Number: +331 56 09 56 38; Email: cleo.bourgeois@aphp.fr

Study Locations

• France
  • Paris, France, 75015
    • Recruiting
    • Hôpital Européen Georges Pompidou
    • Contact: Jean-Luc MD Diehl, PhD; Phone Number: +331 56 09 32 13; Email: jean-luc.diehl@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Xenios AG
• Investigators: Study Chair: Jean-Luc Diehl, PhD, AP-HP, Hôpital Européen Georges Pompidou, Paris

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2022
• Primary Completion (Anticipated): February 1, 2023
• Study Completion (Anticipated): February 1, 2023

Study Registration Dates

• First Submitted: July 31, 2021
• First Submitted That Met QC Criteria: October 1, 2021
• First Posted (Actual): October 15, 2021

Study Record Updates

• Last Update Posted (Actual): May 13, 2022
• Last Update Submitted That Met QC Criteria: May 12, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: COPD; ARDS; ECCO2R; Willebrand factor
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Disease Attributes; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Disease Progression; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: APHP180481; DR-2020-302 (Other Identifier: Commission Nationale de l'Informatique et des Libertés); 2020-A00156-33 (Other Identifier: Agence nationale de sécurité du médicament et des produits de santé)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Individual participant data (IPD) that underlie results in publication could be shared. IPD detailed in the protocol of a planned metaanalysis could be shared
• IPD Sharing Time Frame: Two years after the last publication

IPD Sharing Access Criteria

Data sharing must be accepted by the sponsor and the PI based on a scientific project and scientific involvement of the PI team. Collaboration will be fostered.

Data sharing must respect the agreements made with funders.

Teams wishing obtain IPD must meet the sponsor and IP team to present scientific (and commercial) purpose, IPD needed, format of data transmission, and timeframe. Technical feasibility and financial support will be discussed before mandatory contractual agreement.

Processing of shared data must comply with European General Data Protection Regulation (GDPR).

• IPD Sharing Supporting Information Type: Study Protocol; Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No