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 ?

NCT02803502 | Unknown

• 1 other identifier: CHUB-PK TGT
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 5

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.

Conditions

Hemophilia

Keywords

thrombin generation test; factor VIII; hemophilia

Outcome Measures

Primary Outcomes (15)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

Study Arms (1)

hemophilia

EXPERIMENTAL

Patients with severe hemophilia (or moderate hemophilia if presence of hemorrhages) under prophylaxy and subjected to a pharmacokinetic profile of factor VIII

Device: Chronometric method; Device: Chromogenic method; Device: Thrombin generation test (TGT)

Interventions

Chronometric method DEVICE

Chronometric method of FVIII dosage on STA-R PLC automate (reactive Cephascreen STAGO, Unicalibrateur STAGO, plasma deficient Cryopep, Controls STAGO)

hemophilia

Chromogenic method DEVICE

Chromogenic FVIII assay method ( "BIOPHEN FVIII: C" and "BIOPHEN Factor IX" of the firm Hyphen BioMed)

hemophilia

Thrombin generation test (TGT) DEVICE

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.

hemophilia

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Brugmann University Hospital: lead

Study Sites (5)

CHU Brugmann

Brussels, 1020, Belgium

RECRUITING

HUDERF

Brussels, 1020, Belgium

RECRUITING

Centre Hospitalier Régional de la Citadelle de Liège

Liège, 4000, Belgium

RECRUITING

CHC de Liège

Liège, 4000, Belgium

RECRUITING

CHU Liège Sart Tilman

Liège, 4000, Belgium

RECRUITING

Related Publications (3)

• 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.

  PMID: 13679651 BACKGROUND

• 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.

  PMID: 21688590 BACKGROUND

• 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.

  PMID: 17635721 BACKGROUND

MeSH Terms

Conditions

Hemophilia A

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Anne Demulder, MD

  CHU Brugmann

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anne Demulder, MD

CONTACT

024773990; Anne.DEMULDER@chu-brugmann.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of clinic

Study Record Dates

• First Submitted: June 14, 2016
• First Posted: June 17, 2016
• Study Start: January 1, 2017
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: July 28, 2023

Record last verified: 2023-07

Locations

BE (5)