Clinical trial NCT03625726: Rôle of the Soluble Endothelial Protein C Receptor in Cirrhosis-associated Hypercoagulability State (EXERCISE)
Official title: Ex Vivo Study of the Role of Soluble Endothelial Protein C Receptor in Cirrhosis-associated Hypercoagulability State
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Cirrhosis
Keywords: cirrhosis
hypercoagulability
thrombin generation assay
soluble Endothelial Protein C Receptor
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
First posted: 2018-08-10
Enrollment: 300
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Exploratory, cross-sectional, case-control pathophysiology study, based on ex vivo treatment of blood samples.
Primary purpose: SCREENING

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Thrombin generation assay (area under the curve/ Endogenous Thrombin Potential) with thrombomodulin.
timeFrame: 24 months
Secondary outcomes:
measure: Thrombin generation assay parameters : peak height
timeFrame: 24 months
measure: Thrombin generation assay parameters : lag time
timeFrame: 24 months
measure: Thrombin generation assay parameters : time to peak
timeFrame: 24 months
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: CHU de Clermont-Ferrand
state: Auvergne
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Armand ABERGEL
role: PRINCIPAL_INVESTIGATOR
References: