TGA (Thrombin Generation Assay) and Prophylaxis in Haemophilia

Study Overview
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Brief Summary
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Haemophilic arthropathy is one of the major complications of severe haemophilia. In order to maintain plasma clotting factor activity levels above 1% and avoid spontaneous joint bleeds and other serious bleeding events, prophylactic factor replacement therapy is used. Because of the high cost and limited availability of clotting factor concentrates, dosing is a crucial issue for prophylaxis therapy. Several studies reported a better correlation between clinical bleeding tendency of patients with haemophilia and thrombin generation assay results compared to FVIII/FIX levels. However there is no specific data showing that thrombin generation may be a better indicator of the clinical efficacy of prophylaxis compared to the conventional FVIII measurement. The main objective of this open, multicentre, prospective study is to compare trough thrombin generation capacity and FVIII levels in severe haemophilia patients and compare these two laboratory results with: the number of spontaneous haemarthroses and other spontaneous serious bleeds occurred in the last 6 months the number of additional FVIII units used in the last 6 months This project requires no change in term of type of treatment : During the study, each patient will be treated by his usual clotting factor at the usual regimen (frequency and dosage). The clinical outcome with the usual prophylaxis regimen will be correlated to TGA results

Official Title
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Thrombin Generation Capacity of Patients With Severe Haemophilia Receiving Prophylaxis

Conditions
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Haemophilia A

Intervention / Treatment
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* Other: Thrombin generation measurement.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe haemophilia A (FVIII < 1 IU/dl) Currently on prophylactic therapy The same prophylaxis regimen in the last six months Age: 2 (with a body weight ≥12.5 kg ) - 45 years Adequate venous access Haemophilia patient's diary or equivalent regularly completed Ability of patient or family (for minors) to give informed consent Subject with health insurance Exclusion Criteria: Age <2 and >45 years Haemophilia A with documented inhibitor in the last 12 months Clinically symptomatic liver disease (historical evidence documented in patient's medical file) Platelet count < 100x109/l Poor venous access Presence of a documented target joint Subject under legal protection measure.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: One arm: patients with severe haemophilia A on prophylaxis<br>Patients with severe haemophilia A (FVIII < 1 IU/dl), currently on prophylactic therapy , having the same prophylaxis regimen in the last six months, aged between 2 (with a body weight ≥12.5 kg ) and 45 years , with adequate venous access, having patient's diary or equivalent regularly completed and able to give informed consent | Other: Thrombin generation measurement.<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The correlation between the trough TGA (ETP) results of severe haemophilia patients who are on prophylaxis and the clinical efficacy of the ongoing prophylaxis regimen will be studied |  | The clinical efficacy of prophylaxis will be evaluated on the basis of the number of spontaneous joint bleeds the number of other relevant spontaneous bleeds and the consumption of clotting factor concentrate in the last 6 months prior to TGA. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The correlation between the trough FVIII:C results of severe haemophilia patients who are on prophylaxis and the clinical efficacy of the ongoing prophylaxis regimen will be studied |  | The clinical efficacy of prophylaxis will be evaluated on the basis of the number of spontaneous joint bleeds the number of other relevant spontaneous bleeds and the consumption of clotting factor concentrate in the last 6 months prior to FVIII. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Haemophilia A, prophylaxis, thrombin generation assay, factor VIII, prophylactic therapy