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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 ?

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ClinicalTrials.gov Identifier: NCT02803502
Recruitment Status : Unknown
Verified November 2017 by Dr Anne Demulder, Brugmann University Hospital.
Recruitment status was:  Recruiting
First Posted : June 17, 2016
Last Update Posted : November 30, 2017
Sponsor:
Information provided by (Responsible Party):
Dr Anne Demulder, 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.

Condition or disease Intervention/treatment Phase
Hemophilia Device: Chronometric method Device: Chromogenic method Device: Thrombin generation test (TGT) Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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 ?
Actual Study Start Date : January 2017
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : July 2020


Arm Intervention/treatment
Experimental: hemophilia
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
Chronometric method of FVIII dosage on STA-R PLC automate (reactive Cephascreen STAGO, Unicalibrateur STAGO, plasma deficient Cryopep, Controls STAGO)

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

Device: 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.




Primary Outcome Measures :
  1. Factor VIII blood concentration - chronometric method [ Time Frame: baseline: at factor VIII injection ]
    Chronometric method of FVIII dosage on STA-R PLC automate (reactive Cephascreen STAGO, Unicalibrateur STAGO, plasma deficient Cryopep, Controls STAGO)

  2. Factor VIII blood concentration - chronometric method [ Time Frame: 30 minutes after factor VIII injection ]
    Chronometric method of FVIII dosage on STA-R PLC automate (reactive Cephascreen STAGO, Unicalibrateur STAGO, plasma deficient Cryopep, Controls STAGO)

  3. Factor VIII blood concentration - chronometric method [ Time Frame: 60 minutes after factor VIII injection ]
    Chronometric method of FVIII dosage on STA-R PLC automate (reactive Cephascreen STAGO, Unicalibrateur STAGO, plasma deficient Cryopep, Controls STAGO)

  4. Factor VIII blood concentration - chronometric method [ Time Frame: 120 minutes after factor VIII injection ]
    Chronometric method of FVIII dosage on STA-R PLC automate (reactive Cephascreen STAGO, Unicalibrateur STAGO, plasma deficient Cryopep, Controls STAGO)

  5. Factor VIII blood concentration - chronometric method [ Time Frame: 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)

  6. Factor VIII blood concentration - Chromogenic method [ Time Frame: baseline: at factor VIII injection ]
    Chromogenic FVIII assay method ( "BIOPHEN FVIII: C" and "BIOPHEN Factor IX" of the firm Hyphen BioMed)

  7. Factor VIII blood concentration - Chromogenic method [ Time Frame: 30 minutes after factor VIII injection ]
    Chromogenic FVIII assay method ( "BIOPHEN FVIII: C" and "BIOPHEN Factor IX" of the firm Hyphen BioMed)

  8. Factor VIII blood concentration - Chromogenic method [ Time Frame: 60 minutes after factor VIII injection ]
    Chromogenic FVIII assay method ( "BIOPHEN FVIII: C" and "BIOPHEN Factor IX" of the firm Hyphen BioMed)

  9. Factor VIII blood concentration - Chromogenic method [ Time Frame: 120 minutes after factor VIII injection ]
    Chromogenic FVIII assay method ( "BIOPHEN FVIII: C" and "BIOPHEN Factor IX" of the firm Hyphen BioMed)

  10. Factor VIII blood concentration - Chromogenic method [ Time Frame: 24h after factor VIII injection ]
    Chromogenic FVIII assay method ( "BIOPHEN FVIII: C" and "BIOPHEN Factor IX" of the firm Hyphen BioMed)

  11. total thrombin generation [ Time Frame: baseline: at 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.

  12. total thrombin generation [ Time Frame: 30 minutes 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.

  13. total thrombin generation [ Time Frame: 60 minutes 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.

  14. total thrombin generation [ Time Frame: 120 minutes 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.

  15. total thrombin generation [ Time Frame: 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.



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02803502


Contacts
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Contact: Anne Demulder, MD 024773990 Anne.DEMULDER@chu-brugmann.be

Locations
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Belgium
CHU Brugmann Recruiting
Brussels, Belgium, 1020
Contact: Anne Demulder, MD    024773990    Anne.DEMULDER@chu-brugmann.be   
Principal Investigator: Anne Demulder, MD         
HUDERF Recruiting
Brussels, Belgium, 1020
Contact: Anne Demulder, MD    02 477 39 90    Anne.DEMULDER@chu-brugmann.be   
Principal Investigator: Anne Demulder, MD         
Centre Hospitalier Régional de la Citadelle de Liège Recruiting
Liège, Belgium, 4000
Contact: Jean-Marc Minon, MD    32 4 223 87 81    jean.marc.minon@chrcitadelle.be   
Principal Investigator: Jean-Marc Minon, MD         
CHC de Liège Recruiting
Liège, Belgium, 4000
Contact: Laure Gilis, MD    04.224.89.90    Laure.gilis@chc.be   
Principal Investigator: Laure Gilis, MD         
CHU Liège Sart Tilman Recruiting
Liège, Belgium, 4000
Contact: Pierre Peters, MD    32 4 366.75.36    pierre.peters@chu.ulg.ac.be   
Principal Investigator: Pierre Peters, MD         
Sponsors and Collaborators
Brugmann University Hospital
Investigators
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Principal Investigator: Anne Demulder, MD CHU Brugmann
Publications:
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Responsible Party: Dr Anne Demulder, Head of clinic, Brugmann University Hospital
ClinicalTrials.gov Identifier: NCT02803502    
Other Study ID Numbers: CHUB-PK TGT
First Posted: June 17, 2016    Key Record Dates
Last Update Posted: November 30, 2017
Last Verified: November 2017
Keywords provided by Dr Anne Demulder, Brugmann University Hospital:
thrombin generation test
factor VIII
hemophilia
Additional relevant MeSH terms:
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Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Thrombin
Hemostatics
Coagulants