Thrombin Generation Assay (TGA) as Predictive Test for Haemostatic. Effectiveness of FVIII Concentrates in Haemophiliac A With Inhibitors
- Conditions
- Severe Hemophilia A With Inhibitor
- Registration Number
- NCT01505946
- Lead Sponsor
- Grifols Italia S.p.A
- Brief Summary
This is an observational, prospective, longitudinal, multicenter, cohort study designed with the scope to verify whether or not TGA may predict effectiveness of different FVIII concentrates class (devoid or rich of VWF) in patient affected by severe or moderately severe inherited haemophilia A and inhibitors.
- Detailed Description
Rationale:
Hemophilia A is a serious and common hereditary bleeding disorder caused by deficiency of coagulation factor VIII (FVIII). Patients with this disease are treated with recombinant factor VIII or factor VIII concentrates derived from plasma.
Administration of exogenous FVIII in 15-35% of cases, cause the formation of antibodies to FVIII (inhibitors) that neutralize the activity of factor VIII, making the treatment ineffective.The development of inhibitors of factor VIII (FVIII) is the most serious and challenging complication of the treatment of hemophilia A and represents the highest economic burden for a chronic disease. Therefore, research is making great efforts to optimize the best therapeutic approach for the disease.
It has been observed that FVIII inhibitors display a wide range of immunoreactivity when tested against different classes of FVIII concentrates (with/without von Willebrand factor -VWF). It has been demonstrated that the different inhibitors reactivity may correlate with different ability of inhibitors to impair thrombin generation, as tested by Thrombin Generation Assay (TGA). In these patients TGA assay might be a tool to predict which FVIII concentrate has the greater haemostatic effectiveness.
It is also uncertain if the different classes of FVIII used in ITI protocols may have a different effectiveness in reducing the occurrence of BT bleedings and if this may correlate to lower reactivity, epitope specificity, VWF content and may be predicted by TGA. It would be very helpful to be able to give an evidence based diagnostic and prognostic instrument, the TGA, to aid physician to optimize the therapy for all inhibitors patients.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- Male
- Target Recruitment
- 25
- Diagnosis of inherited, severe (FVIII:C < 1%) or moderately severe haemophilia A (FVIII ≤ 2%)
- Any age
- Ability to comply with study methods and willingness to participate to the study
- Written informed consent.
FOR THE LOW RESPONDERS COHORT
- Documented low anamnestic response after FVIII exposure (FVIII inhibitors titre >0.6 and < 5 BU/ml tested by Bethesda assay, Nijmegen modification). It will be included in this study those patients who have never been submitted to ITI and also those patients who have completed ITI with partial success (defined as inhibitors titre >0.6 and < 5 BU/ml and no increase in the INH titer > 5 BU over treatment with FVIII)
INCLUSION CRITERIA FOR THE HIGH RESPONDERS COHORT
- Documented high response after FVIII exposure (FVIII inhibitors titre > 5 BU/ml tested by Bethesda assay, Nijmegen modification). It will be included in this study those patients who are potential candidates to a first or rescue ITI.
- Any historical peak ≥ 5 BU
- Diagnosis of acquired haemophilia
- Diagnosis of inherited mild haemophilia A (FVIII > 2%)
- Life expectancy lower than 1 year
- Psychiatric illness and any other conditions may impair ability to comply with study methods
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Thrombin generation result 12 months Thrombin generation results of the TGA applied on plasma patients whith inhibitor matched with different class of FVIII concentrate
- Secondary Outcome Measures
Name Time Method Incidence of all breakthrough (BT) bleedings 12 months events/month
Total FVIII dose required to treat the patients 12 months (IU/year)
Use of bypassing agents 12 months incidence of BT bleedings who require bypassing agents (events/months) average dose of bypassing agents (or days of treatment) needed to treat BT bleedings total dose of bypassing agent (and days of treatment) required overall (IU/year) and (days of treatment/year)
ITI outcome only for patient under this kind of treatment 3 years % of Success (total, partial success or failure will be defined as in ITI study protocol) Time to tolerance (months), defined as the time to ITI success (total/partial)
Epitope mapping results 12 months epitope mapping test on the plasma patient during the therapy for a follow-up period of 12 month
the inhibitor titre course 12 months
Trial Locations
- Locations (15)
Ospedale Civile dell' Annunziata
🇮🇹Cosenza, Calabria, Italy
Az. Universitaria Policlinico "Federico II" Dip. Assist. di Clinica Medica
🇮🇹Napoli, Campania, Italy
UO Angiologia e Malattie della Coagulazione "Marino Golinelli" Az Osp. Policlinico S. Orsola Malpighi
🇮🇹Bologna, Emilia Romagna, Italy
Azienda Ospedaliera "Santa Maria della Misericordia"
🇮🇹Udine, Friuli Venezia Giulia, Italy
Ematologia Dipartimento di Biotecnologie Cellulari Università La Sapienza - Policlinico Umberto I
🇮🇹Rome, Lazio, Italy
Ospedale Pediatrico Bambino Gesù di Roma
🇮🇹Rome, Lazio, Italy
Università Cattolica - Policlinico A. Gemelli
🇮🇹Rome, Lazio, Italy
Azienda Ospedialiera Ospedale Infantile Regina Margherita - S.Anna
🇮🇹Turin, Piemonte, Italy
Ospedale Le Molinette "S. G. Battista"
🇮🇹Turin, Piemonte, Italy
Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari
🇮🇹BAri, Puglia, Italy
Scroll for more (5 remaining)Ospedale Civile dell' Annunziata🇮🇹Cosenza, Calabria, ItalyFilomena Daniele, MDPrincipal Investigator