Does the Thrombin Generation Test Performed During the Pharmacokinetic Profile of the Substitutive Factor VIII Bring Benefits to the Personalized Treatment of Pediatric Patients and Adult Hemophilia A Patients Under Prophylaxis ?

Not Applicable

Recruiting

• Conditions: Hemophilia
• Interventions: Device: Chronometric method; Device: Chromogenic method; Device: Thrombin generation test (TGT)

• Registration Number: NCT02803502
• Lead Sponsor: Brugmann University Hospital

Brief Summary

In the context of hemophilia, it is well know that the level of factor VIII alone does not reflect the clinical phenotype of the patients in an accurate way. At equal factor VIII levels, certain patients will bleed more than others.

The thrombin generation test (TGT) is a test that seems to provide a better prediction of the overall hemostatic status of an individual patient. In a previous study, the investigators have established normal reference values of the thrombin generation curve in children aged 6 months to 16 years and adults. The goal was to evaluate the use of this test in different clinical contexts and in severe hemophilia patients in particular. A pilot study showed that the patients having a thrombin generation \<150 had a severe phenotype, whether those who received an appropriate prophylaxy had a thrombin generation superior to 150.

Moreover, the investigators now have access to a software tool that allows them to individually determine the pharmacokinetic profile of the factor VIII injected to each patient. The factor VIII concentration is measured at injection and 30 minutes, 1 hour, 2 hours and 24 hours afterwards. The introduction of these concentrations in the software allows to obtain the half-life of factor for a given patient, the maximum peak, and the minimum factor level (though level). The injected dosis might be sufficient (disappearance of substantial diminution of the bleedings) or unsufficient (persisting bleeding) for a given patient.

This study aims:

* to measure the pharmacokinetic profile of factor VIII by two different methods, the time-based method and the chromogenic method

* to correlate the results with the TGT results obtained at the same time points and determine which method gives the best correlation

* to link the clinical symptomatology (improved symptomatology or not) with the TGT results

* to determine which minimal TGT result is linked to a minimal bleeding rate

* to adapt the prophylactic dosis of the patient in a personalized way.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-06-14
• Study First Submitted QC: 2016-06-14
• Study First Posted: 2016-06-17
• Study Start: 2017-01
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-27
• Last Update Posted: 2023-07-28
• Primary Completion: 2024-12
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Patients with severe or moderate hemophilia, on prophylaxis, and suffering from bleedings.

Exclusion Criteria

• Patients with difficult venous access
• Patients who have had surgery or trauma in the month before, patients with acute disease (infection, inflammation)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
hemophilia	Chronometric method	Patients with severe hemophilia (or moderate hemophilia if presence of hemorrhages) under prophylaxy and subjected to a pharmacokinetic profile of factor VIII
hemophilia	Chromogenic method	Patients with severe hemophilia (or moderate hemophilia if presence of hemorrhages) under prophylaxy and subjected to a pharmacokinetic profile of factor VIII
hemophilia	Thrombin generation test (TGT)	Patients with severe hemophilia (or moderate hemophilia if presence of hemorrhages) under prophylaxy and subjected to a pharmacokinetic profile of factor VIII

Primary Outcome Measures

Name	Time	Method
Factor VIII blood concentration - chronometric method	24h after factor VIII injection	Chronometric method of FVIII dosage on STA-R PLC automate (reactive Cephascreen STAGO, Unicalibrateur STAGO, plasma deficient Cryopep, Controls STAGO)
Factor VIII blood concentration - Chromogenic method	24h after factor VIII injection	Chromogenic FVIII assay method ( "BIOPHEN FVIII: C" and "BIOPHEN Factor IX" of the firm Hyphen BioMed)
total thrombin generation	24h after factor VIII injection	the measurement of thrombin generation is performed by the technique of calibrated and automated Thrombinography (CAT) developed by Hemker HC. This technique allows the simultaneous analysis of multiple samples using a fluorometer (Fluoroscan Ascent, ThermoLabsystems OY, Helsinki, Finland) and a Thrombinoscope® software that converts the fluorescence intensity obtained by concentration of active thrombin.

Trial Locations

Locations (5)

CHC de Liège; 🇧🇪 Liège, Belgium

CHU Brugmann; 🇧🇪 Brussels, Belgium

HUDERF; 🇧🇪 Brussels, Belgium

Centre Hospitalier Régional de la Citadelle de Liège; 🇧🇪 Liège, Belgium

CHU Liège Sart Tilman; 🇧🇪 Liège, Belgium