Rôle of the Soluble Endothelial Protein C Receptor in Cirrhosis-associated Hypercoagulability State (EXERCISE)

Study Overview
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Brief Summary
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Cirrhosis is a condition in which the liver does not function properly due to long-term damage. This damage is characterized by the replacement of normal liver tissue by scar tissue. The liver carries out several necessary functions, including synthesis of proteins participating in blood coagulation process. Some of these proteins contribute to coagulation and others make blood more fluid. In healthy people there is a balance between the two. In cirrhotic patient, there is an imbalance inducing hypercoagulation (hypercoagulability state). Cirrhotic patients are so known to be at risk of vein thrombosis (for example portal vein thrombosis: clot in hepatic vein). Mechanisms leading to this imbalance are unclear. Studies need to be completed to improve patient's management. The EPCRs (Endothelial Protein C Receptor soluble) takes part in blood coagulation process. Previous studies have shown that blood levels of EPCRs are increased in patients with cirrhosis. The primary purpose of the study is to evaluate if the EPCRs could play a role in cirrhosis-associated hypercoagulability state.

Detailed Description
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Three groups will be constitued: one with cirrhotic patients, one with healthy volunteers, and one with patients with hepatocellular carcinoma, a form of liver cancer (previous studies have also shown that blood levels of EPCRs are increased in these patients). All participants will undergo a unique visit at hospital. An informed consent will be obtained before any related study procedures*. * procedures: physical examination (including height, weight, waist measurement), vital signs (blood pressure, heart rate, temperature), medical history, concomitant medication, blood sample.

Official Title
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Ex Vivo Study of the Role of Soluble Endothelial Protein C Receptor in Cirrhosis-associated Hypercoagulability State

Conditions
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Cirrhosis

Intervention / Treatment
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* Biological: Thrombin generation assay (in vitro)


Participation Criteria
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Eligibility Criteria
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Patients with cirrhosis Inclusion criteria : Male, age 18 or older Cirrhosis, defined by: prothombin time ≤ 70% +/- liver dysmorphism +/- Fibroscan > 12.5 kPa +/- histology +/- portal hypertension associated with hepatocellular insufficiency Cirrhosis associated with hepatitis B or C, or alcoholic liver disease, or non alcoholic steato hepatitis Measurable portal flow by ultrasound doppler Child Pugh score A,B or C, without acute infection or acute bleeding Signed written informed consent Affiliation to french social security system Exclusion criteria : Known history of vein thrombosis Known family history (in first-degree relative) of spontaneous thrombosis Partial or complete portal system vein thrombosis Uncontrolled infection after 7-day course of antibiotics Anticoagulant intake Hepatocellular carcinoma Protected or deprived of liberty adult Any medical or surgical history that could interfere with the study, as judged by the investigator Blood transfusion within 7 days Participation in a clinical trial for drug Healthy volunteers Inclusion criteria : Male, age 18 or older Body Mass Index between 18 and 30 kg/m2 Normal physical examination Willing and able to comply with requirements of the study Agree to be registered in the french national registry for healthy volunteers Signed written informed consent Affiliation to french social security system Exclusion criteria : Any medical or surgical history that could interfere with the study, as judged by the investigator Participation in a clinical trial for drug Protected or deprived of liberty adult Known history of vein thrombosis Known family history (in first-degree relative) of spontaneous thrombosis Anticoagulant intake Patients with hepatocellular carcinoma (HCC) Inclusion criteria : Male, age 18 or older Histological diagnosis of HCC, or use of BCLC criteria for diagnosis Treatment naïve HCC Measurable portal flow by ultrasound doppler For patients with cirrhosis: Child Pugh score A,B or C, without acute infection or acute bleeding Signed written informed consent Affiliation to french social security system Exclusion criteria : Known history of vein thrombosis Known family history (in first-degree relative) of spontaneous thrombosis Partial or complete portal system vein thrombosis For patients with cirrhosis: uncontrolled infection after 7-day course of antibiotics Anticoagulant intake Protected or deprived of liberty adult Any medical or surgical history that could interfere with the study, as judged by the investigator Blood transfusion within 7 days Prior treated malignancy within the previous 2 years (except basal cell and squamous cell skin cancer, and superficial bladder cancer) Participation in a clinical trial for drug

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Exploratory, cross-sectional, case-control pathophysiology study, based on ex vivo treatment of blood samples.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: patients with cirrhosis<br>pathophysiology study, blood sample | Biological: Thrombin generation assay (in vitro)<br>* One blood sample.<br>|
| Placebo Comparator: healthy volunteers<br>pathophysiology study, blood sample | Biological: Thrombin generation assay (in vitro)<br>* One blood sample.<br>|
| Placebo Comparator: patients with hepatocellular carcinoma<br>pathophysiology study, blood sample | Biological: Thrombin generation assay (in vitro)<br>* One blood sample.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thrombin generation assay (area under the curve/ Endogenous Thrombin Potential) with thrombomodulin. |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thrombin generation assay parameters : peak height |  | 24 months | 
| Thrombin generation assay parameters : lag time |  | 24 months | 
| Thrombin generation assay parameters : time to peak |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cirrhosis, hypercoagulability, thrombin generation assay, soluble Endothelial Protein C Receptor