Thrombin Generation Parameters and Bleeding in Patients Treated With Anticoagulants for Cancer Associated Thrombosis

Official title

Association Between Thrombin Generation Parameters and the Risk of Bleeding in Patients Treated With Anticoagulants for Cancer Associated Thrombosis (CAT) (a Multicenter Study)

Overview

Pulmonary embolism, the second leading cause of death in cancer patients, is effectively treated with anticoagulants. In patients with cancer-associated thrombosis (CAT), the use of anticoagulants is associated with 10 to 15% of bleeding in the first 6 months. Most of the guidelines propose to integrate the bleeding risk in the choice of therapies. Thrombin generation assay (TGA) reflects an overall hemostatic response and could be a useful biomarker. Proven on the thrombotic side in the CAT population, useful in the assessment of the bleeding risk of hemophiliac patients, the TGA is emerging as a tool. The investigators to measure TGA in cancer patients included prospectively, having recently developed a CAT and to evaluate the association between the measurement and the risk of hemorrhagic complication under anticoagulant during the first 6 month of treatment.

Detailed description

Pulmonary embolism, the second leading cause of death in cancer patients, is effectively treated with anticoagulants. In patients with cancer-associated thrombosis (CAT), the use of anticoagulants is associated with 10 to 15% of bleeding in the first 6 months. Most of the guidelines propose to integrate the bleeding risk in the choice of therapies. Existing models for predicting anticoagulant associated bleeding risk applied to the CAT patients are not very predictive (AUC\<0.60). Thrombin generation assay (TGA) reflects an overall hemostatic response and could be a useful biomarker. Proven on the thrombotic side in the CAT population, useful in the assessment of the bleeding risk of hemophiliac patients, the TGA is emerging as a tool. The investigators wish to measure TGA in cancer patients included prospectively, having recently developed a CAT and to evaluate the association between the measurement and the risk of hemorrhagic complication under anticoagulant during the first 6 month of treatment.

Interventions

• Biological Thrombin Generation Assay (TGA)
  Hemostasis is a complex process in which genetic or environmental conditions can cause shifts either towards pro-thrombotic states resulting in thrombosis, or towards pro-hemorrhagic states resulting in uncontrolled bleeding. Tests to assess a more global hemostatic profile, such as the TGA, have appeared as a more reliable alternative to assess the real hemostatic capacity of an individual. TGA is a global dynamic assay simultaneously and continuously measuring thrombin generation. It monitors

Primary outcome measures

• The measurement of the area under the curve ( endogenious thrombin potential) nMxmin [Time frame: during the first 6 months of treatment]
• the measurement of the lag time unit = seconds [Time frame: during the first 6 months of treatment]
• the measurement of the peak height unit = nm [Time frame: during the first 6 months of treatment]
• the measurement of the time to peak unit = seconds [Time frame: during the first 6 months of treatment]

Secondary outcome measures (3)

• Effect of adding TGT results on the performance of bleeding risk prediction scores [Time frame: Month 1; Month 6]
• Occurrence of clinically relevant bleeding between m1 and m6, based on the change in TGT [Time frame: Month 1; Month 6]
• Occurrence of an event of interest under treatment [Time frame: Month : 1 to 6]

Eligibility criteria

Inclusion criteria

• Patients with active cancer, as defined by current French recommendations (Mahé I et al Rev Mal Respir 2021)
• Presenting acute proximal deep vein thrombosis of the lower limb (DVT) and/or proximal pulmonary embolism (at least segmental) (PE), confirmed by objective tests (Doppler ultrasound in the event of DVT; lung scintigraphy or CT scan in the event of PE)
• No contraindication for anticoagulant treatment at a curative dose at the time of inclusion

Exclusion criteria

• Patients participating in a therapeutic clinical trial with a blinded therapy or an open-label therapeutic trial who are included in the experimental treatment group.
• Patients already on anticoagulant at a curative dose for valvular or rhythmic embolic disease or a history of venous thromboembolic disease
• Hematological malignancies
• Patients with a contraindication to anticoagulant treatment on inclusion
• Patient whose relay by DOAC has already been carried out.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Other

Study locations

France · 4 centers

• Chu Clermont-Ferrand — Clermont-Ferrand
• CHU de Grenoble — Grenoble
• HCL — Lyon
• Chu St-Etienne — Saint-Etienne

Identifiers

NCT: NCT06386107 · 23PH188 · 2023-A02175-40

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗