Association Between the Level of EV-TF and the Occurence of Pulmonary Embolism in Patients With ARDS (THROMBO-EVTF)

Association Between the Level of Extracellular Vesicle - Associated Tissue Factor and the Occurence of Pulmonary Embolism in Patients With Acute Respiratory Distress Syndrome

In this study, 120 patients with Acute Respiratory Distress Syndrome (ARDS) will be included on a two years-period in an intensive care unit (Assistance Publique des Hôpitaux de Marseille, France). Those patients will benefit from a blood test at inclusion in order to measure several coagulation biomarkers, including EV-TF. Subsequently, these patients will be treated according to the usual practices of the department, following recommendations. Patients who received an injected CT scan between Day 5 and Day 28 will be divided into two groups based on the presence or absence of a pulmonary embolism on imaging. The measured values of EV-TF levels and other studied biomarkers will be compared between these two groups in order to detect a possible association between them and the diagnosis of pulmonary embolism. It should be noted that patients receiving an injected CT-scan between Day 5 and Day 7 will be included in the main analysis while those receiving it between Day 8 and Day 28 will be included in the secondary analysis. Others will be excluded from any analysis. At the same time, several collections of clinical data will be carried out: on Day 1, Day 7, Day 28, and on the day of the CT scan if it is performed at another time.

Study Overview

• Status: Recruiting
• Conditions: Acute Respiratory Distress Syndrome
• Intervention / Treatment: Other: Blood sample

• Study Type: Observational
• Enrollment (Estimated): 170

Contacts and Locations

• Study Contact: Name: Giovanni Bousquet, MD; Phone Number: 33 0491964252; Email: giovanni.bousquet@ap-hm.fr
• Study Contact Backup: Name: Christophe Guervilly, MD; Phone Number: 33 0491965842; Email: christophe.guervilly@ap-hm.fr

Study Locations

• France
  • Marseille, France, 13015
    • Recruiting
    • Service Médecine Intensive et Réanimation
    • Contact: Giovanni Bousquet, MD; Phone Number: 33 0491964252; Email: giovanni.bousquet@ap-hm.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with ARDS admitted to the intensive care unit

Description

Inclusion Criteria:

• Patient 18 years of age or older,
• Patient who has given his/her non-opposition to participate in this study, or alternatively, patient for whom a relative has given his/her non-opposition to participate in this study,
• Patient admitted to intensive care for less than 24 hours,

• Patient with ARDS according to the Berlin criteria,

  • Hypoxemia with PaO2/FiO2 ratio ≤ 300 on mechanical ventilation under PEEP ≥ 5 cmH2O,
  • Bilateral alveolar-interstitial opacities on chest imaging (chest X-ray or CT),
  • Exclusion of a cardiogenic cause on echocardiography,
  • Acute or subacute onset within 7 days based on the clinical-radiological profile.

Exclusion Criteria:

• Positive SARS-CoV-2 PCR in a pharyngeal or respiratory sample (cytobacteriological examination of sputum, bronchial aspiration or bronchoalveolar lavage) prior to admission to the intensive care unit,
• Patient with a pathology affecting the coagulation process or endothelial function (hemophilia, von Willebrand disease, etc.),
• Patient receiving curative anticoagulant treatment before admission to the intensive care unit,
• Patient undergoing extracorporeal veno-venous respiratory assistance (ECMO-VV) before admission to the intensive care unit,
• Patient undergoing extra-renal purification with systemic anticoagulation with heparin before admission to the intensive care unit,
• Persons referred to in articles L. 1121-5 to L. 1121-8 of the Public Health Code (minor patients, adult patients under tutorship or guardianship, patients deprived of their liberty, pregnant or nursing women),
• Moribund patients for whom the life expectancy is less than 24 hours according to the opinion of the investigating physician.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with pulmonary embolism; The presence of pulmonary embolism is determined from a CT scan realized between Day 5 and Day 28.	Other: Blood sample; Additional blood samples will be taken on a catheter, used for standard care.
Patients without pulmonary embolism; The absence of pulmonary embolism is determined from a CT scan realized between Day 5 and Day 28.	Other: Blood sample; Additional blood samples will be taken on a catheter, used for standard care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in EV-TF levels at inclusion between patients with and without pulmonary embolism at day 7 postinclusion	EV-TF level is determined from a blood sample realized at inclusion and the presence of pulmonary embolism from a CT scan realized during the first week of patient care in intensive care unit.	Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in EV-TF levels at inclusion between patients with and without pulmonary embolism at day 28 postinclusion	EV-TF level is determined from a blood sample realized at inclusion. The presence of pulmonary embolism is determined from a CT scan realized during the first 28 days of patient care in intensive care unit.	Day 28
Difference in EV-TF levels at inclusion between patients with and without venous thrombo-embolic disease at day 7 postinclusion	EV-TF level is determined from a blood sample realized at inclusion. The presence of venous thrombo-embolic disease is determined from an echo-doppler realized during the first week of patient care in intensive care unit.	Day 7
Difference in EV-TF levels at inclusion between patients with and without venous thrombo-embolic disease at day 28 postinclusion	EV-TF level is determined from a blood sample realized at inclusion. The presence of venous thrombo-embolic disease is determined from an echo-doppler realized during the first 28 days of patient care in intensive care unit.	Day 28
Association between EV-TF levels and patient prognosis	EV-TF level is determined from a blood sample realized at inclusion. Patient prognosis is based on the duration of intensive care unit stay, on the duration of hospital stay, and on death.	Day 60
Association between EV-TF level and alveolar dead space at inclusion	EV-TF level is determined from a blood sample realized at inclusion. Alveolar dead space is obtained by volumetric capnography at inclusion.	Day 1
Association between EV-TF level and alveolar dead space at day 7 postinclusion	EV-TF level is determined from a blood sample realized at inclusion. Alveolar dead space is obtained by volumetric capnography at day 7 postinclusion.	Day 7
Association between EV-TF level and alveolar dead space at day 28 postinclusion	EV-TF level is determined from a blood sample realized at inclusion. Alveolar dead space is obtained by volumetric capnography at day 28 postinclusion.	Day 28
Association between EV-TF level and alveolar dead space at thoracic CT scan day	EV-TF level is determined from a blood sample realized at inclusion. Alveolar dead space is obtained by volumetric capnography at day of CT-scan.	Between day 5 and day 28
Optimal threshold value of EV-TF associated with the occurrence of pulmonary embolism.	EV-TF level is determined from a blood sample realized at inclusion. Occurrence of pulmonary embolism is determined from a CT scan realized during the first 28 days of patient care in intensive care unit.	Day 28
Optimal threshold value of EV-TF associated with the occurrence of venous thrombo-embolic disease.	EV-TF level is determined from a blood sample realized at inclusion. Occurrence of venous thrombo-embolic disease pulmonary embolism is determined from an echo-doppler realized during the first 28 days of patient care in intensive care unit.	Day 28
Optimal threshold value of EV-TF associated with the occurrence of death	EV-TF level is determined from a blood sample realized at inclusion. Occurrence of death is measured during the 2 months of follow up (or when the patient is discharged from hospital, if earlier).	Day 60
Predictive value of Willebrand antigen at inclusion on the occurrence of pulmonary embolism at day 7.	This biomarker is quantified from the blood sample collected at inclusion. The presence of pulmonary embolism from a CT scan realized during the first week of patient care in intensive care unit.	Day 7
Predictive value of ADAMTS13 activity at inclusion on the occurrence of pulmonary embolism at day 7.	This biomarker is quantified from the blood sample collected at inclusion. The presence of pulmonary embolism from a CT scan realized during the first week of patient care in intensive care unit.	Day 7
Predictive value of Willebrand antigen at inclusion on the occurrence of pulmonary embolism at day 28.	This biomarker is quantified from the blood sample collected at inclusion. The presence of pulmonary embolism is determined from a CT scan realized during the first 28 days of patient care in intensive care unit.	Day 28
Predictive value of ADAMTS13 activity at inclusion on the occurrence of pulmonary embolism at day 28.	This biomarker is quantified from the blood sample collected at inclusion. The presence of pulmonary embolism is determined from a CT scan realized during the first 28 days of patient care in intensive care unit.	Day 28
Predictive value of Willebrand antigen at inclusion on the occurrence of venous thrombo-embolic disease at day 7.	This biomarker is quantified from the blood sample collected at inclusion. The presence of venous thrombo-embolic disease is determined from an echo-doppler realized during the first week of patient care in intensive care unit.	Day 7
Predictive value of ADAMTS13 activity at inclusion on the occurrence of venous thrombo-embolic disease at day 7.	This biomarker is quantified from the blood sample collected at inclusion. The presence of venous thrombo-embolic disease is determined from an echo-doppler realized during the first week of patient care in intensive care unit.	Day 7
Predictive value of Willebrand antigen at inclusion on the occurrence of venous thrombo-embolic disease at day 28.	This biomarker is quantified from the blood sample collected at inclusion. The presence of venous thrombo-embolic disease is determined from an echo-doppler realized during the first 28 days of patient care in intensive care unit.	Day 28
Predictive value of ADAMTS13 activity at inclusion on the occurrence of venous thrombo-embolic disease at day 28.	This biomarker is quantified from the blood sample collected at inclusion. The presence of venous thrombo-embolic disease is determined from an echo-doppler realized during the first 28 days of patient care in intensive care unit.	Day 28
Predictive value of Willebrand antigen at inclusion on the patients' death.	This biomarker is quantified from the blood sample collected at inclusion. Occurrence of death is measured during the 2 months of follow up (or when the patient is discharged from hospital, if earlier).	Day 60
Predictive value of ADAMTS13 activity at inclusion on the patients' death.	This biomarker is quantified from the blood sample collected at inclusion. Occurrence of death is measured during the 2 months of follow up (or when the patient is discharged from hospital, if earlier).	Day 60
Predictive value of circulating levels of antithrombin (coagulation inhibitor) at inclusion on the occurrence of pulmonary embolism at day 7.	This biomarker is quantified from the blood sample collected at inclusion. The presence of pulmonary embolism from a CT scan realized during the first week of patient care in intensive care unit.	Day 7
Predictive value of circulating levels of protein C (coagulation inhibitor) at inclusion on the occurrence of pulmonary embolism at day 7.	This biomarker is quantified from the blood sample collected at inclusion. The presence of pulmonary embolism from a CT scan realized during the first week of patient care in intensive care unit.	Day 7
Predictive value of circulating levels of protein S (coagulation inhibitor) at inclusion on the occurrence of pulmonary embolism at day 7.	This biomarker is quantified from the blood sample collected at inclusion. The presence of pulmonary embolism from a CT scan realized during the first week of patient care in intensive care unit.	Day 7
Predictive value of D-dimers (circulating fibrinolytic potential) at inclusion on the occurrence of pulmonary embolism at day 7.	This biomarker is quantified from the blood sample collected at inclusion. The presence of pulmonary embolism from a CT scan realized during the first week of patient care in intensive care unit.	Day 7
Predictive value of fibrin monomers (circulating fibrinolytic potential) at inclusion on the occurrence of pulmonary embolism at day 7.	This biomarker is quantified from the blood sample collected at inclusion. The presence of pulmonary embolism from a CT scan realized during the first week of patient care in intensive care unit.	Day 7
Predictive value of circulating PAI-1 (circulating fibrinolytic potential) at inclusion on the occurrence of pulmonary embolism at day 7.	This biomarker is quantified from the blood sample collected at inclusion. The presence of pulmonary embolism from a CT scan realized during the first week of patient care in intensive care unit.	Day 7
Predictive value of circulating levels of antithrombin (coagulation inhibitor) at inclusion on the occurrence of pulmonary embolism at day 28.	This biomarker is quantified from the blood sample collected at inclusion. The presence of pulmonary embolism is determined from a CT scan realized during the first 28 days of patient care in intensive care unit.	Day 28
Predictive value of circulating levels of protein C (coagulation inhibitor) at inclusion on the occurrence of pulmonary embolism at day 28.	This biomarker is quantified from the blood sample collected at inclusion. The presence of pulmonary embolism is determined from a CT scan realized during the first 28 days of patient care in intensive care unit.	Day 28
Predictive value of circulating levels of protein S (coagulation inhibitor) at inclusion on the occurrence of pulmonary embolism at day 28.	This biomarker is quantified from the blood sample collected at inclusion. The presence of pulmonary embolism is determined from a CT scan realized during the first 28 days of patient care in intensive care unit.	Day 28
Predictive value of D-dimers (circulating fibrinolytic potential) at inclusion on the occurrence of pulmonary embolism at day 28.	This biomarker is quantified from the blood sample collected at inclusion. The presence of pulmonary embolism is determined from a CT scan realized during the first 28 days of patient care in intensive care unit.	Day 28
Predictive value of fibrin monomers (circulating fibrinolytic potential) at inclusion on the occurrence of pulmonary embolism at day 28.	This biomarker is quantified from the blood sample collected at inclusion. The presence of pulmonary embolism is determined from a CT scan realized during the first 28 days of patient care in intensive care unit.	Day 28
Predictive value of circulating PAI-1 (circulating fibrinolytic potential) at inclusion on the occurrence of pulmonary embolism at day 28.	This biomarker is quantified from the blood sample collected at inclusion. The presence of pulmonary embolism is determined from a CT scan realized during the first 28 days of patient care in intensive care unit.	Day 28
Predictive value of circulating levels of antithrombin (coagulation inhibitor) at inclusion on the occurrence of venous thrombo-embolic disease at day 7.	This biomarker is quantified from the blood sample collected at inclusion. The presence of venous thrombo-embolic disease is determined from an echo-doppler realized during the first week of patient care in intensive care unit.	Day 7
Predictive value of circulating levels of protein C (coagulation inhibitor) at inclusion on the occurrence of venous thrombo-embolic disease at day 7.	This biomarker is quantified from the blood sample collected at inclusion. The presence of venous thrombo-embolic disease is determined from an echo-doppler realized during the first week of patient care in intensive care unit.	Day 7
Predictive value of circulating levels protein S (coagulation inhibitor) at inclusion on the occurrence of venous thrombo-embolic disease at day 7.	This biomarker is quantified from the blood sample collected at inclusion. The presence of venous thrombo-embolic disease is determined from an echo-doppler realized during the first week of patient care in intensive care unit.	Day 7
Predictive value of D-dimers (circulating fibrinolytic potential) at inclusion on the occurrence of venous thrombo-embolic disease at day 7.	This biomarker is quantified from the blood sample collected at inclusion. The presence of venous thrombo-embolic disease is determined from an echo-doppler realized during the first week of patient care in intensive care unit.	Day 7
Predictive value of fibrin monomers (circulating fibrinolytic potential) at inclusion on the occurrence of venous thrombo-embolic disease at day 7.	This biomarker is quantified from the blood sample collected at inclusion. The presence of venous thrombo-embolic disease is determined from an echo-doppler realized during the first week of patient care in intensive care unit.	Day 7
Predictive value of circulating PAI-1 (circulating fibrinolytic potential) at inclusion on the occurrence of venous thrombo-embolic disease at day 7.	This biomarker is quantified from the blood sample collected at inclusion. The presence of venous thrombo-embolic disease is determined from an echo-doppler realized during the first week of patient care in intensive care unit.	Day 7
Predictive value of circulating levels of antithrombin (coagulation inhibitor) at inclusion on the occurrence of venous thrombo-embolic disease at day 28.	This biomarker is quantified from the blood sample collected at inclusion. The presence of venous thrombo-embolic disease is determined from an echo-doppler realized during the first 28 days of patient care in intensive care unit.	Day 28
Predictive value of circulating levels of protein C (coagulation inhibitor) at inclusion on the occurrence of venous thrombo-embolic disease at day 28.	This biomarker is quantified from the blood sample collected at inclusion. The presence of venous thrombo-embolic disease is determined from an echo-doppler realized during the first 28 days of patient care in intensive care unit.	Day 28
Predictive value of circulating levels of protein S (coagulation inhibitor) at inclusion on the occurrence of venous thrombo-embolic disease at day 28.	This biomarker is quantified from the blood sample collected at inclusion. The presence of venous thrombo-embolic disease is determined from an echo-doppler realized during the first 28 days of patient care in intensive care unit.	Day 28
Predictive value of D-dimers (circulating fibrinolytic potential) at inclusion on the occurrence of venous thrombo-embolic disease at day 28.	This biomarker is quantified from the blood sample collected at inclusion. The presence of venous thrombo-embolic disease is determined from an echo-doppler realized during the first 28 days of patient care in intensive care unit.	Day 28
Predictive value of fibrin monomers (circulating fibrinolytic potential) at inclusion on the occurrence of venous thrombo-embolic disease at day 28.	This biomarker is quantified from the blood sample collected at inclusion. The presence of venous thrombo-embolic disease is determined from an echo-doppler realized during the first 28 days of patient care in intensive care unit.	Day 28
Predictive value of circulating PAI-1 (circulating fibrinolytic potential) at inclusion on the occurrence of venous thrombo-embolic disease at day 28.	This biomarker is quantified from the blood sample collected at inclusion. The presence of venous thrombo-embolic disease is determined from an echo-doppler realized during the first 28 days of patient care in intensive care unit.	Day 28
Predictive value of of circulating levels of antithrombin (coagulation inhibitor) at inclusion on the patients' death.	This biomarker is quantified from the blood sample collected at inclusion. Occurrence of death is measured during the 2 months of follow up (or when the patient is discharged from hospital, if earlier).	Day 60
Predictive value of of circulating levels of protein C (coagulation inhibitor) at inclusion on the patients' death.	This biomarker is quantified from the blood sample collected at inclusion. Occurrence of death is measured during the 2 months of follow up (or when the patient is discharged from hospital, if earlier).	Day 60
Predictive value of of circulating levels of protein S (coagulation inhibitor) at inclusion on the patients' death.	This biomarker is quantified from the blood sample collected at inclusion. Occurrence of death is measured during the 2 months of follow up (or when the patient is discharged from hospital, if earlier).	Day 60
Predictive value of D-dimers (circulating fibrinolytic potential) at inclusion on the patients' death.	This biomarker is quantified from the blood sample collected at inclusion. Occurrence of death is measured during the 2 months of follow up (or when the patient is discharged from hospital, if earlier).	Day 60
Predictive value of fibrin monomers (circulating fibrinolytic potential) at inclusion on the patients' death.	This biomarker is quantified from the blood sample collected at inclusion. Occurrence of death is measured during the 2 months of follow up (or when the patient is discharged from hospital, if earlier).	Day 60
Predictive value of circulating PAI-1 (circulating fibrinolytic potential) at inclusion on the patients' death.	This biomarker is quantified from the blood sample collected at inclusion. Occurrence of death is measured during the 2 months of follow up (or when the patient is discharged from hospital, if earlier).	Day 60

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Investigators: Study Director: François Cremieux, AP-HM

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2023
• Primary Completion (Estimated): November 7, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: May 3, 2023
• First Submitted That Met QC Criteria: May 3, 2023
• First Posted (Actual): May 11, 2023

Study Record Updates

• Last Update Posted (Actual): November 2, 2023
• Last Update Submitted That Met QC Criteria: October 31, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Embolism and Thrombosis; Lung Injury; Infant, Premature, Diseases; Syndrome; Embolism; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Pulmonary Embolism
• Other Study ID Numbers: RCAPHM22_0440; ID-RCB (Other Identifier: 2023-A01937-38)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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