This research program is initiated to evaluate and document data on the success of ITI in 300 haemophilia A patients with newly developed or already existing FVIII-inhibitors (also patients who might potentially have failed in earlier ITIs), which will be treated with ITI - preferably high-dose based on individualized product selection, in order to improve management of this potentially devastating complication of haemophilia treatment.
In order to investigate the role of in vitro tests on individual ITI success rate in patients undergoing ITI, the inhibitor plasma samples can be assayed against different FVIII concentrates using the following in vitro tests: Batch selection, Thrombin generation assay (TGA), Thrombin Generation Test (TGT) to monitor FVIII efficacy, Epitope mapping,IgG Subclasses specific for FVIII, Immunogenotyping.
Based on the decision of the treating physicians in the participating centres, male patients at any age suffering from severe (FVIII activity < 1%), moderate (FVIII activity >1% - 5%), or mild (FVIII activity > 5%) haemophilia A will be included into this post marketing observation if relevant inhibitor levels (> 0.6 BU) have been detected, or - in case of an inhibitor level <0.6 BU - with reduced recovery or half-life of FVIII.
The observation is also open for patients who failed an earlier ITI attempt.
Female
all male patients with haemophilia A and inhibitor
Cohort
Prospective
Not listed
The efficacy of ITI, the primary endpoint of this observation, is defined according to the following criteria (The measure is a composite).: Inhibitor titre <0.6 BU, Incremental recovery of FVIII in the normal range,Half-life of FVIII > 7 hours.
The efficacy of ITI, the primary endpoint of this observation, is defined according to the following criteria (The measure is a composite): * Inhibitor titre \<0.6 BU (at least 2 consecutive determinations) * Incremental recovery of FVIII in the normal range (\> 80% of normal) with samples taken prior to and 15 or 30 minutes after FVIII treatment. * Half-life of FVIII \> 7 hours (blood samples for FVIII determination should be taken prior to and 15 or 30 minutes, 1, 2, 4, 8 and either 12 or 24 hours after FVIII treatment. Complete Success: All three criteria above met. Partial Success: Two of the three criteria above met. Partial Response: One of the three criteria above met. Partial Failure of ITI-treatment: Inhibitor still present, but titre has decreased to \<5 BU. Complete Failure of ITI-treatment: None of the above mentioned criteria met, and the inhibitor titre is still ≥5 BU.
The following secondary endpoints will also be evaluated.The measure is a composite.
The following secondary endpoints will be evaluated: * the success rates of the different types of products selected for ITI, especially those of pure and VWF-stabilized FVIII concentrates * the maintenance in case of complete or partial ITI success * the clinical relevance of the individual in vitro testing and batch selection, the selected type of concentrate will be correlated with the ITI success * the adverse drug reactions and possibly ITI efficacy related events occurring during the ITI-treatment phase * the compliance with the ITI-treatment regimen * the time necessary to achieve complete or partial success of individualized ITI * the impact of inhibitor titres at start of ITI and during the course of ITI, including the peak titre of the inhibitor * the number of break-through bleeding events during the course of ITI-treatment.
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Haemophilia Centre Rhine Main
Lead sponsor
University of Bonn
Collaborator
Skane University Hospital
Collaborator
Hopital Cardiologique Louis Pradel, Unité d'Hemostase Clinique Bron
Collaborator
