Characterization of the microVAScular Dysfunction in Covid-19 ARDS (VASCOV)

Characterization of the microVAScular Dysfunction in COvid-19 ARDS

The primary endpoint of this research is to establish that the alveolar dead space is significantly higher in patients with COVID-19 ARDS, compared to patients with non-COVID-19 ARDS.

Secondarily, the investigators want to establish the prognostic value of the alveolar-dead space (measured iteratively) in patients with COVID-19 and non-COVID-19 ARDS, to establish the respective influences of the biological parameters of endothelial damage, of the biological parameters of coagulopathy, of the parameters set on the artificial ventilator on the value of the alveolar dead space; in ARDS patients with COVID-19 and non-COVID-19 ARDS, to establish the prognostic value of the laboratory parameters of endothelial damage and coagulopathy in patients with COVID-19 and non-COVID-19 ARDS.

Study Overview

• Status: Recruiting
• Conditions: ARDS, Human; COVID-19 Acute Respiratory Distress Syndrome
• Intervention / Treatment: Diagnostic test: alveolar dead-space quantification; Diagnostic test: Coagulation activation and impaired fibrinolysis explorations; Diagnostic test: Endothelial activation / endothelial senescence

Detailed Description

Endothelial damage and coagulation activation at the lung microvascular level may play an important role in the physiopathology of the COVID-19 ARDS. The project aims to prospectively investigate both bedside pulmonary physiological markers and biological markers of coagulopathy and endothelial dysfunction in COVID-19 and non-COVID-19 ARDS patients.

• Study Type: Observational
• Enrollment (Anticipated): 40

Contacts and Locations

• Study Contact: Name: Josephine Braun, PhD; Phone Number: 01 44 84 17 38; Email: josephine.braun@aphp.fr

Study Locations

• France
  • Paris, France, 75015
    • Recruiting
    • Hôpital Européen Georges Pompidou
    • Contact: Diehl Jean-Luc, PhD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with moderate or severe ARDS linked or not with covid-19

Description

Inclusion Criteria:

• Age> 18 years old
• Invasive mechanical ventilation in place for less than 48 hours
• Severe or moderate ARDS (defined according to the Berlin classification)
• Virological confirmation by PCR of SARS-CoV-2 infection (ARDS COVID-19)
• Lack of virological confirmation by PCR of SARS-CoV-2 infection (ARDS not linked to COVID-19)
• Patient information

Exclusion Criteria:

• Massive pulmonary embolism
• Chronic respiratory failure under long-term oxygen therapy
• Dying patient

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
non-COVID-19 ARDS patients; 20 patients with acute respiratory distress syndrome (ARDS) unrelated to COVID-19	Diagnostic test: alveolar dead-space quantification; measurement of alveolar dead-space based on volumetric capnography; Diagnostic test: Coagulation activation and impaired fibrinolysis explorations; blood sampling: Fibrinolytic components; NETs components; Elastase-derived fragments of proteins of interest; Diagnostic test: Endothelial activation / endothelial senescence; circulating endothelial cells, E-selectin, endoglin, LVEF-A, LVEFR-2, Angiopoietin -1 and -2, cKit and SDF-1 Willebrand factor (activity, antigen, multimeric analysis )
COVID-19 ARDS patients; 20 patients with acute respiratory distress syndrome (ARDS) linked to COVID-19	Diagnostic test: alveolar dead-space quantification; measurement of alveolar dead-space based on volumetric capnography; Diagnostic test: Coagulation activation and impaired fibrinolysis explorations; blood sampling: Fibrinolytic components; NETs components; Elastase-derived fragments of proteins of interest; Diagnostic test: Endothelial activation / endothelial senescence; circulating endothelial cells, E-selectin, endoglin, LVEF-A, LVEFR-2, Angiopoietin -1 and -2, cKit and SDF-1 Willebrand factor (activity, antigen, multimeric analysis )

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prognostic value of alveolar dead space	Recording the exhaled CO2 curve (side-stream capnography method) and volume curve, as determined by the mechanical ventilator, and computing the signals with the arterial CO2 partial pressure, reflecting the partial pressure of CO2 in the alveoli participating in gas exchanges), determined on arterial blood gas (ABG) sampling.	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prognostic value of the alveolar dead space (measured iteratively)	To establish the link between alveolar dead-space values and Day 20 mortality	20 days
Prognostic value of the alveolar dead space (measured iteratively)	To establish the link between alveolar dead-space values and Day 20 mortality and Day-28 invasive ventilator-free days.	28 days
Level of circulating endothelial cells	To describe the biological parameters of endothelial damage and prognostic value	Up to 28 days
Level of progenitor cells	To describe the biological parameters of endothelial damage and prognostic value	Up to 28 days
Level of circulating stem cells	To describe the biological parameters of endothelial damage and prognostic value	Up to 28 days
Level of endothelial proteomics	To describe the biological parameters of endothelial damage and prognostic value	Up to 28 days
Level of D-dimers	To describe the biological parameters of endothelial damage and prognostic value	Up to 28 days
Level of Willebrand Factor	To describe the biological parameters of endothelial damage and prognostic value	Up to 28 days
Level of components of the fibrinolytic system	To describe the biological parameters of endothelial damage and prognostic value	Up to 28 days
Level of fragments of plasminogen	To describe the biological parameters of endothelial damage and prognostic value	Up to 28 days
Level of the components of the NETs (Neutrophil Extracellular Traps)	To describe the biological parameters of endothelial damage and prognostic value	Up to 28 days
Survival rate		90 days

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, Vanstapel A, Werlein C, Stark H, Tzankov A, Li WW, Li VW, Mentzer SJ, Jonigk D. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med. 2020 Jul 9;383(2):120-128. doi: 10.1056/NEJMoa2015432. Epub 2020 May 21.
• Diehl JL, Peron N, Chocron R, Debuc B, Guerot E, Hauw-Berlemont C, Hermann B, Augy JL, Younan R, Novara A, Langlais J, Khider L, Gendron N, Goudot G, Fagon JF, Mirault T, Smadja DM. Respiratory mechanics and gas exchanges in the early course of COVID-19 ARDS: a hypothesis-generating study. Ann Intensive Care. 2020 Jul 16;10(1):95. doi: 10.1186/s13613-020-00716-1.

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2021
• Primary Completion (Anticipated): September 10, 2022
• Study Completion (Anticipated): September 10, 2022

Study Registration Dates

• First Submitted: July 19, 2021
• First Submitted That Met QC Criteria: October 11, 2021
• First Posted (Actual): October 12, 2021

Study Record Updates

• Last Update Posted (Actual): January 19, 2022
• Last Update Submitted That Met QC Criteria: January 17, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: circulating endothelial cells; pulmonary biological markers; alveolar dead-space
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; COVID-19; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: APHP210693; 2021-A01339-32 (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. 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; 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