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 ?

Hemophilia Clinical Trial

Official title:

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 ?

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02803502
• Other study ID #: CHUB-PK TGT
• Status: Recruiting
• Phase: N/A
• Start date: January 2017
• Est. completion date: December 2024

Study information

• Verified date: July 2023
• Source: Brugmann University Hospital
• Contact: Anne Demulder, MD
• Phone: 024773990
• Email: Anne.DEMULDER[@]chu-brugmann.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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)

Related Conditions & MeSH terms

• Hemophilia
• Hemophilia A

Intervention

Device:
• Chronometric method
Chronometric method of FVIII dosage on STA-R PLC automate (reactive Cephascreen STAGO, Unicalibrateur STAGO, plasma deficient Cryopep, Controls STAGO)
• Chromogenic method
Chromogenic FVIII assay method ( "BIOPHEN FVIII: C" and "BIOPHEN Factor IX" of the firm Hyphen BioMed)
• Thrombin generation test (TGT)
Briefly: 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. The reagent "PPP-reagent Low" respectively containing 1pm FT and 4µM phospholipid (PL) as a final concentration will be used.

Locations

Country	Name	City	State
Belgium	CHU Brugmann	Brussels
Belgium	HUDERF	Brussels
Belgium	Centre Hospitalier Régional de la Citadelle de Liège	Liège
Belgium	CHC de Liège	Liège
Belgium	CHU Liège Sart Tilman	Liège

Sponsors (1)

Lead Sponsor	Collaborator
Brugmann University Hospital

Country where clinical trial is conducted

Belgium, 

References & Publications (3)

Filippin L, Debaugnies F, Noubouossie D, Le PQ, Ferster A, Demulder A. [Thrombin generation test: establishment of reference values according to age and tissue factor concentration is essential before implementation into the laboratory]. Rev Med Brux. 2011 Mar-Apr;32(2):69-73. French. — View Citation

Hemker HC, Giesen P, AlDieri R, Regnault V, de Smed E, Wagenvoord R, Lecompte T, Beguin S. The calibrated automated thrombogram (CAT): a universal routine test for hyper- and hypocoagulability. Pathophysiol Haemost Thromb. 2002 Sep-Dec;32(5-6):249-53. doi: 10.1159/000073575. — View Citation

van den Berg HM, De Groot PH, Fischer K. Phenotypic heterogeneity in severe hemophilia. J Thromb Haemost. 2007 Jul;5 Suppl 1:151-6. doi: 10.1111/j.1538-7836.2007.02503.x. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Factor VIII blood concentration - chronometric method	Chronometric method of FVIII dosage on STA-R PLC automate (reactive Cephascreen STAGO, Unicalibrateur STAGO, plasma deficient Cryopep, Controls STAGO)	baseline: at factor VIII injection
Primary	Factor VIII blood concentration - chronometric method	Chronometric method of FVIII dosage on STA-R PLC automate (reactive Cephascreen STAGO, Unicalibrateur STAGO, plasma deficient Cryopep, Controls STAGO)	30 minutes after factor VIII injection
Primary	Factor VIII blood concentration - chronometric method	Chronometric method of FVIII dosage on STA-R PLC automate (reactive Cephascreen STAGO, Unicalibrateur STAGO, plasma deficient Cryopep, Controls STAGO)	60 minutes after factor VIII injection
Primary	Factor VIII blood concentration - chronometric method	Chronometric method of FVIII dosage on STA-R PLC automate (reactive Cephascreen STAGO, Unicalibrateur STAGO, plasma deficient Cryopep, Controls STAGO)	120 minutes after factor VIII injection
Primary	Factor VIII blood concentration - chronometric method	Chronometric method of FVIII dosage on STA-R PLC automate (reactive Cephascreen STAGO, Unicalibrateur STAGO, plasma deficient Cryopep, Controls STAGO)	24h after factor VIII injection
Primary	Factor VIII blood concentration - Chromogenic method	Chromogenic FVIII assay method ( "BIOPHEN FVIII: C" and "BIOPHEN Factor IX" of the firm Hyphen BioMed)	baseline: at factor VIII injection
Primary	Factor VIII blood concentration - Chromogenic method	Chromogenic FVIII assay method ( "BIOPHEN FVIII: C" and "BIOPHEN Factor IX" of the firm Hyphen BioMed)	30 minutes after factor VIII injection
Primary	Factor VIII blood concentration - Chromogenic method	Chromogenic FVIII assay method ( "BIOPHEN FVIII: C" and "BIOPHEN Factor IX" of the firm Hyphen BioMed)	60 minutes after factor VIII injection
Primary	Factor VIII blood concentration - Chromogenic method	Chromogenic FVIII assay method ( "BIOPHEN FVIII: C" and "BIOPHEN Factor IX" of the firm Hyphen BioMed)	120 minutes after factor VIII injection
Primary	Factor VIII blood concentration - Chromogenic method	Chromogenic FVIII assay method ( "BIOPHEN FVIII: C" and "BIOPHEN Factor IX" of the firm Hyphen BioMed)	24h after factor VIII injection
Primary	total thrombin generation	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.	baseline: at factor VIII injection
Primary	total thrombin generation	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.	30 minutes after factor VIII injection
Primary	total thrombin generation	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.	60 minutes after factor VIII injection
Primary	total thrombin generation	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.	120 minutes after factor VIII injection
Primary	total thrombin generation	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.	24h after factor VIII injection