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

Acute Respiratory Distress Syndrome Clinical Trial

— THROMBO-EVTF  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05855317
• Other study ID #: RCAPHM22_0440
• Secondary ID: ID-RCB
• Status: Recruiting
• Start date: October 31, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: October 2023
• Source: Assistance Publique Hopitaux De Marseille
• Contact: Giovanni Bousquet, MD
• Phone: 0491964252
• Email: giovanni.bousquet[@]ap-hm.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 170
• Est. completion date: December 31, 2025
• Est. primary completion date: November 7, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Embolism
• Pulmonary Embolism
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

Other:
• Blood sample
Additional blood samples will be taken on a catheter, used for standard care.

Locations

Country	Name	City	State
France	Service Médecine intensive et réanimation	Marseille

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique Hopitaux De Marseille

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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