Clinical trial NCT02803502: 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: 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 ?
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Hemophilia
Keywords: thrombin generation test
factor VIII
hemophilia
Lead sponsor: Brugmann University Hospital
Sponsor class: OTHER
First posted: 2016-06-17
Enrollment: 50
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.


Eligibility 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)

Primary outcomes:
measure: Factor VIII blood concentration - chronometric method
timeFrame: baseline: at factor VIII injection
measure: Factor VIII blood concentration - chronometric method
timeFrame: 30 minutes after factor VIII injection
measure: Factor VIII blood concentration - chronometric method
timeFrame: 60 minutes after factor VIII injection
measure: Factor VIII blood concentration - chronometric method
timeFrame: 120 minutes after factor VIII injection
measure: Factor VIII blood concentration - chronometric method
timeFrame: 24h after factor VIII injection
measure: Factor VIII blood concentration - Chromogenic method
timeFrame: baseline: at factor VIII injection
measure: Factor VIII blood concentration - Chromogenic method
timeFrame: 30 minutes after factor VIII injection
measure: Factor VIII blood concentration - Chromogenic method
timeFrame: 60 minutes after factor VIII injection
measure: Factor VIII blood concentration - Chromogenic method
timeFrame: 120 minutes after factor VIII injection
measure: Factor VIII blood concentration - Chromogenic method
timeFrame: 24h after factor VIII injection
measure: total thrombin generation
timeFrame: baseline: at factor VIII injection
measure: total thrombin generation
timeFrame: 30 minutes after factor VIII injection
measure: total thrombin generation
timeFrame: 60 minutes after factor VIII injection
measure: total thrombin generation
timeFrame: 120 minutes after factor VIII injection
measure: total thrombin generation
timeFrame: 24h after factor VIII injection
Secondary outcomes:
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: CHU Brugmann
city: Brussels
country: Belgium
facility: HUDERF
city: Liège
country: Belgium
facility: Centre Hospitalier Régional de la Citadelle de Liège
city: Liège
country: Belgium
facility: CHC de Liège
city: Liège
country: Belgium
facility: CHU Liège Sart Tilman
Study officials:
affiliation: CHU Brugmann
name: Anne Demulder, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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.