Evaluation of Fibrin Structure Marker in Cancer Patients Treated and Not Treated With LMWH

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to assess the fibrin structure marker in the plasma of cancer patients, treated or not treated with LMWH at prophylactic or therapeutic doses, in order to determine the venous thromboembolic risk. The occurrence of thromboembolic events in patients without treatment and in patients under LMWH treatment will be recorded, depending on the location and type of cancer, metastases, and treatment of cancer.

Detailed Description
-----------------
Rationale. Venous thromboembolism (VTE) is a major complication often encountered in oncology and onco-hematology, and difficult to handle. It involves the activation of coagulation with the generation of fibrin and plasmin and angiogenesis activation. Low molecular weight heparins (LMWH) are used to treat cancer associated thrombosis. Furthermore, they could have an inhibitory effect on tumor progression. International recommendations on the treatment and prophylaxis of the disease allow a better management of VTE in patients with cancer. Its prevalence is high, occurring in 15-20% of the patients. It remains the second leading cause of death after cancer. LMWH at therapeutic dosage for at least three months and preferably six months without oral bridging is the reference treatment for VTE, which showed a 50% reduction in the risk of recurrent thromboembolism without increasing the hemorrhagic risk. In case of VTE recurrence under LMWH treatment, the dose can be increased by 10%. Preliminary results suggest that the fibrin structure marker would predict the hemorrhagic or thromboembolic risk, and show that LMWH has a dose-dependent effect on fibrin structure. This marker is evaluated as a tool to guide the treatment of VTE by LMWH in patients with cancer. Main objective. To assess the fibrin structure marker in the plasma of cancer patients, treated or not treated with LMWH at prophylactic doses at enrollment or therapeutic doses, to determine the venous thromboembolic risk. The occurrence of thromboembolic events in patients without treatment or of recurrent thromboembolic events in patients under LMWH treatment will be studied, depending on the location and type of cancer, metastases, and treatment of cancer. Patients. At least 300 adult patients over 18 years with all types of malignancies documented before or during therapeutic treatment with LMWH for thromboembolic event. They will be monitored every month in consultation or during hospitalization in the Internal Medicine Department. The patients under prophylaxis with LMWH at enrollment will also be included and classified in the group of prophylactic patients. The patients who receive prophylactic treatment during will be included and classified in the group of untreated patients. Will not be included: patients with sepsis, severe infections, pneumonia, surgery, suspected thromboembolic event related to catheter implantation, vitamin K antagonists (VKA) in progress, and those with impossible follow-up. The study is conducted in compliance with French regulation after ethics approval, the authorization for processing personal data (Commission Nationale de l'Informatique et des Libertés, 8, rue Vivienne CS 30223 75083 Paris Cedex 02) receipt number 1867686 v 0, date 18 June 2015. Reference algorithm. Patients will be supported for the diagnosis and specific treatment of cancer (with or without metastases), according to the daily practice. The baseline risk score is the Khorana score of clinical probability, based on clinical criteria. A thromboembolic event has to be diagnosed according to standard imaging criteria (spiral computed tomography CT, proximal lower limb venous compression ultrasonography US) by clinicians who will not have knowledge of the result of the fibrin structure marker. Biological parameters to be studied. The following tests will be carried out on frozen citrated plasma or serum, without knowledge of the clinical data and the conclusion of a diagnostic of thromboembolic event: Structure of the fibrin using coag-lysis method, measured at baseline and every month for all patients, by one site, using prototype assays Anti-FXa activity measured at baseline and every month only for patients treated with LMWH at therapeutic doses, FVIII:C and TFPI for coagulation activation, DDimers and PAI-1 for fibrinolysis resistance, Fibrin assay for inflammation and hypercoagulation evaluation, all measured at baseline and every 3 months for all patients.

Official Title
-----------------
Evaluation of Fibrin Structure Marker in Cancer Patients Treated and Not Treated With LMWH

Conditions
-----------------
Malignant Tumor

Intervention / Treatment
-----------------
* Other: Fibrin Structure


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: patients with non-opposition to participate in the evaluation patients from Internal Medicine Department patients affected with all types of malignancies, treated or not with LMWH Exclusion Criteria: patients treated with VKA or with recent surgery (within one month) patients with a condition known to cause a coagulation activation status other than cancer (sepsis, pneumonia,..)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group I<br>Patients without LMWH treatment. A thromboembolic event has to be diagnosed according to standard imaging criteria (spiral computed tomography CT, proximal lower limb venous compression ultrasonography US) by clinicians who will not have knowledge of the result of the fibrin structure marker. The following assays will be performed for these patients : Fibrin Structure measured at baseline and every month using prototype assays Other markers activity : sFVIII:C and TFPI for coagulation activation, DDimers and PAI-1 for fibrinolysis resistance and fibrin assay, all measured at baseline and every 3 months. | Other: Fibrin Structure<br>* Modifications of Fibrin Structure in patients who have developed VTE in comparison with patients without VTE.<br>|
| Group II<br>Patients with LMWH treatment at prophylactic dose at enrollment only. A thromboembolic event has to be diagnosed according to standard imaging criteria (spiral computed tomography CT, proximal lower limb venous compression ultrasonography US) by clinicians who will not have knowledge of the result of the fibrin structure marker. The following assays will be performed for these patients : Fibrin Structure measured at baseline and every month using prototype assays, Anti-FXa activity measured at baseline and every month, Other markers activity : FVIII:C and TFPI for coagulation activation, DDimers and PAI-1 for fibrinolysis resistance and fibrin assay, all measured at baseline and every 3 months. | Other: Fibrin Structure<br>* Modifications of Fibrin Structure in patients who have developed VTE in comparison with patients without VTE.<br>|
| Group III<br>Patients with LMWH treatment at therapeutic dose. A thromboembolic event has to be diagnosed according to standard imaging criteria (spiral computed tomography CT, proximal lower limb venous compression ultrasonography US) by clinicians who will not have knowledge of the result of the fibrin structure marker. The following assays will be performed for these patients : Fibrin Structure measured at baseline and every month using prototype assays, Anti-FXa activity measured at baseline and every month, Other markers activity : FVIII:C and TFPI for coagulation activation, DDimers and PAI-1 for fibrinolysis resistance and fibrin assay, all measured at baseline and every 3 months. | Other: Fibrin Structure<br>* Modifications of Fibrin Structure in patients who have developed VTE in comparison with patients without VTE.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dynamic evolution of the optical density delta (ODD) | Evolution of the optical density delta (ODD) and temporal parameters in patients who have developed VTE in comparison with those without VTE; variations of the Fibrin Structure parameters in comparison with either coagulation activation or fibrinolysis resistance assays, or fibrin assay. Changes of the Fibrin structure parameters in patients of group III in comparison with group I and/or group II. | 36 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clotting time (s) | Evolution of the optical density delta (ODD) and temporal parameters in patients who have developed VTE in comparison with those without VTE; variations of the Fibrin Structure parameters in comparison with either coagulation activation or fibrinolysis resistance assays, or fibrin assay. Changes of the Fibrin structure parameters in patients of group III in comparison with group I and/or group II. | 36 Months | 
| Fibrin formation time (s) | Evolution of the optical density delta (ODD) and temporal parameters in patients who have developed VTE in comparison with those without VTE; variations of the Fibrin Structure parameters in comparison with either coagulation activation or fibrinolysis resistance assays, or fibrin assay. Changes of the Fibrin structure parameters in patients of group III in comparison with group I and/or group II. | 36 Months | 
| Lysis time (s) | Evolution of the optical density delta (ODD) and temporal parameters in patients who have developed VTE in comparison with those without VTE; variations of the Fibrin Structure parameters in comparison with either coagulation activation or fibrinolysis resistance assays, or fibrin assay. Changes of the Fibrin structure parameters in patients of group III in comparison with group I and/or group II. | 36 Months | 
| Duration and level of the plateau (s) | Evolution of the optical density delta (ODD) and temporal parameters in patients who have developed VTE in comparison with those without VTE; variations of the Fibrin Structure parameters in comparison with either coagulation activation or fibrinolysis resistance assays, or fibrin assay. Changes of the Fibrin structure parameters in patients of group III in comparison with group I and/or group II. | 36 Months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cancer, Thromboembolic event, Fibrin Structure, LMWH