EVIGE: Evaluation of the Inter-center Variability of the Measurement of Thrombin Generation by the ST Genesia System

Sponsor

University Hospital, Clermont-Ferrand (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05422157

Collaborator

Diagnostica Stago (Industry)

Enrollment

Location

Anticipated Duration (Months)

3.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The thrombin generation test is a global test for the study of coagulation that allows the fine study of the balance between procoagulant and anticoagulant factors. For many years, it has been performed in laboratories by semi-automated techniques, sometimes using in-house reagents, which led to a high variability and did not allow multicenter studies. Recently, an automated device for the evaluation of thrombin generation has been placed on the market (ST-Genesia), allowing a better standardization of the technique. In order to allow multicenter studies, which are essential for the routine positioning of the thrombin generation test, the inter-center variability must be evaluated, as a priority, in the pathologies for which the test is routinely positioned.

Thrombin generation (TG) assays are long-established research tools in hemostasis. They are used for both fundamental and clinical research, but a multiplicity of test methodologies limits the large adoption of TG due to the variability of results despite the attempts to standardize practices.

Several publications already exist to evaluate its analytical performances, and thereby demonstrate that the test automation also allows its democratization to reach acceptable performances It also enables the evaluation of the device in various indications such as, for example, the evaluation of the effect of direct oral anticoagulants or the evaluation of the risk of breast cancer recurrence.

The confirmation of these anterior results allows further clinical investigations in larger cohorts. However, the absence of interchangeability between the two systems indicates that the results will need to be more rugged through multicenter studies on ST Genesia.

Condition or Disease	Intervention/Treatment	Phase
Patients Without a Medical History of Thrombosis or Hemorrhage Hemophilic Patient Patient With FV Leiden Mutation Patient With Cirrhosis Patient on Anticoagulant

Detailed Description

A preliminary step in the development of multi-center protocols is to confirm that inter-center variability is acceptable on ST Genesia, and even more acceptable than it was on Calibrated Automated Thrombogram (CAT). Since the variability of the results can be attributed to analytical, pre-analytical and inter-individual biological variabilities, it has been agreed that the evaluation that we will conduct will focus only on the analytical variability and will therefore be carried out on the same samples, collected and prepared in the sponsoring center of the study, and distributed in the form of frozen aliquots to the different co-investigating centers.

The evaluation of this inter-center variability of this new device will allow, if satisfactory, to propose multicenter studies. These are essential in order to position the thrombin generation test in routine in these various promising clinical contexts.

Study Design

Study Type:

Observational

Anticipated Enrollment :

65 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Evaluation of the Inter-center Variability of the Measurement of Thrombin Generation by the ST Genesia System

Anticipated Study Start Date :

Jul 31, 2022

Anticipated Primary Completion Date :

Jul 31, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Control No intervention. Collection of additional blood volume (50 mL) during blood tests provided as part of the usual medical care.
Hemophilia No intervention. Collection of additional blood volume (50 mL) during blood tests provided as part of the usual medical care.
FV Leiden No intervention. Collection of additional blood volume (50 mL) during blood tests provided as part of the usual medical care.
Cirrhosis No intervention. Collection of additional blood volume (50 mL) during blood tests provided as part of the usual medical care.
Anticoagulation No intervention. Collection of additional blood volume (50 mL) during blood tests provided as part of the usual medical care.

Outcome Measures

Primary Outcome Measures

Evaluate the inter-center analytical variability of the thrombin generation measurement on ST Genesia, on different types of normo-, hypo- or hyper-coagulable samples. [at the time of inclusion]
Assessing the analytical variability of the thrombin generation measurement on ST Genesia, compared to that observed on CAT, on different groups of patients

Secondary Outcome Measures

Assessment of inter-center analytical variability on ST Genesia related to different reagent lots, for centers with multiple reagent lots. [at the time of inclusion]
Measure of the thrombin generation in absolute value
Comparing the analytical variability between centers observed on the same samples on the reference system, the Calibrated Automated Thrombogram, for centers also equipped with this device [at the time of inclusion]
Investigate the differences between thrombin generation measurements on CAT and ST genesia

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Major patient, male or female
Affiliated to a social security system
In capacity to express informed consent to participate in research
Control group: 5 men, 5 women without oral contraception, 5 women with oral contraception and apparently healthy with a respect to hemostasis (no history of thrombosis or significant bleeding on examination)
Hemophilia groups: - 5 hemophiliacs A (treated or untreated), with predictable FVIII:C levels between < 1% and 40%.
5 hemophiliacs B (treated or not), with predictable FIX:C levels between < 1% and 40%.
FV Leiden group: 5 patients known to be heterozygous or homozygous for the R506Q mutation of the F5 gene (the so-called "Factor V Leiden" mutation)
Cirrhosis group: - 5 patients with Child-Pugh A
5 patients with Child-Pugh B
5 patients with Child-Pugh C
Anticoagulation group: - 5 patients on anti-vitamin K therapy for at least 1 month, with INR between 2 and 4
5 patients on apixaban for at least 1 week
5 patients on rivaroxaban for at least 1 week
5 patients on dabigatran for at least 1 week
5 patients on low molecular weight heparin for at least 1 day

Exclusion Criteria:

Refusal to participate
Patient under protective measures (guardianship, curatorship) or under judicial protection
Minor patients
Moderate to end-stage renal failure
Proven inflammatory state/infectious syndrome (body temperature > 38°C and/or clinical signs suggestive of infection) during or in the week prior to collection, at the discretion of the investigator
Transfusion in the week prior to collection
Pregnant or breastfeeding woman
Contraception by estrogen-progestin, except for the control group concerned
Anticoagulation of less than one week, except for the anticoagulation group
Control group: - Presence of drug treatment known to interfere with hemostasis
Presence of a pathology known to interfere with hemostasis such as renal or hepatic insufficiency
Presence of a history of venous thromboembolic disease or diagnosed hemorrhagic disease
Predicted inclusion hemoglobin level < 7g/L
Hemophilic groups: - Presence of anti FVIII or anti FIX inhibitors
Treatment with emicizumab
Predicted inclusion hemoglobin level < 7g/L
FV Leiden group: - Presence of anticoagulant therapy at the time of collection
Predicted baseline hemoglobin < 7g/L
Anticoagulation group: - Anticoagulant therapy not stabilized as determined by the practitioner
Presence of a therapeutic relaunch in progress
Hemoglobin at predicted inclusion < 9-10g/L
Cirrhosis group: Predicted inclusion hemoglobin level < 7g/L