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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

Tracking Information
First Submitted Date  ICMJE June 14, 2016
First Posted Date  ICMJE June 17, 2016
Last Update Posted Date November 30, 2017
Actual Study Start Date  ICMJE January 2017
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 14, 2016)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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 ?
Official Title  ICMJE 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 ?
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Hemophilia
Intervention  ICMJE
  • 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.
Study Arms  ICMJE Experimental: hemophilia
Patients with severe hemophilia (or moderate hemophilia if presence of hemorrhages) under prophylaxy and subjected to a pharmacokinetic profile of factor VIII
Interventions:
  • Device: Chronometric method
  • Device: Chromogenic method
  • Device: Thrombin generation test (TGT)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: June 14, 2016)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2020
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02803502
Other Study ID Numbers  ICMJE CHUB-PK TGT
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dr Anne Demulder, Brugmann University Hospital
Study Sponsor  ICMJE Brugmann University Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Anne Demulder, MD CHU Brugmann
PRS Account Brugmann University Hospital
Verification Date November 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP