Clinical trial NCT02552381: Evaluation of Fibrin Structure Marker in Cancer Patients Treated and Not Treated With LMWH
Official title: Evaluation of Fibrin Structure Marker in Cancer Patients Treated and Not Treated With LMWH
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Malignant Tumor
Keywords: Cancer
Thromboembolic event
Fibrin Structure
LMWH
Lead sponsor: Diagnostica Stago R&D
Sponsor class: INDUSTRY
Collaborators: name: Hôpital Louis Mourier
name: Hopital Lariboisière
First posted: 2015-09-17
Enrollment: 389
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients from Internal Medicine Department, in a French Hospital

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.

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,..)

Primary outcomes:
measure: Dynamic evolution of the optical density delta (ODD)
timeFrame: 36 Months
Secondary outcomes:
measure: Clotting time (s)
timeFrame: 36 Months
measure: Fibrin formation time (s)
timeFrame: 36 Months
measure: Lysis time (s)
timeFrame: 36 Months
measure: Duration and level of the plateau (s)
timeFrame: 36 Months
Other outcomes:
Locations:
city: Colombes
country: France
facility: Internal Medecine Department - Adults Pole and Hematology Laboratory Hôpital Louis Mourier (AP-HP)
Study officials:
affiliation: Université of Paris 7 - Paris Diderot
name: Isabelle Mahe, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Diagnostica Stago
name: Geneviève Contant, PhD
role: STUDY_DIRECTOR
References:
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citation: Pieters M, Philippou H, Undas A, de Lange Z, Rijken DC, Mutch NJ; Subcommittee on Factor XIII and Fibrinogen, and the Subcommittee on Fibrinolysis. An international study on the feasibility of a standardized combined plasma clot turbidity and lysis assay: communication from the SSC of the ISTH. J Thromb Haemost. 2018 May;16(5):1007-1012. doi: 10.1111/jth.14002. Epub 2018 Apr 15. No abstract available.
citation: Longstaff C; subcommittee on fibrinolysis. Development of Shiny app tools to simplify and standardize the analysis of hemostasis assay data: communication from the SSC of the ISTH. J Thromb Haemost. 2017 May;15(5):1044-1046. doi: 10.1111/jth.13656. Epub 2017 Mar 17. No abstract available.