Thrombin Generation Assay (TGA) as Predictive Test for Haemostatic. Effectiveness of FVIII Concentrates in Haemophiliac A With Inhibitors (PredicTGA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Grifols Italia S.p.A
Sponsor:
Collaborator:
Thrombinoscope
Information provided by (Responsible Party):
Grifols Italia S.p.A
ClinicalTrials.gov Identifier:
NCT01505946
First received: January 5, 2012
Last updated: June 14, 2013
Last verified: June 2013

January 5, 2012
June 14, 2013
March 2012
December 2015   (final data collection date for primary outcome measure)
Thrombin generation result [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Thrombin generation results of the TGA applied on plasma patients whith inhibitor matched with different class of FVIII concentrate
Same as current
Complete list of historical versions of study NCT01505946 on ClinicalTrials.gov Archive Site
  • Epitope mapping results [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    epitope mapping test on the plasma patient during the therapy for a follow-up period of 12 month
  • Incidence of all breakthrough (BT) bleedings [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    events/month
  • Total FVIII dose required to treat the patients [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    (IU/year)
  • the inhibitor titre course [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Use of bypassing agents [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    % 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)
Same as current
Not Provided
Not Provided
 
Thrombin Generation Assay (TGA) as Predictive Test for Haemostatic. Effectiveness of FVIII Concentrates in Haemophiliac A With Inhibitors
Thrombin Generation Assay (TGA) as Predictive Test for Haemostatic Effectiveness of Factor VIII (FVIII) Concentrates in Patients Affected by Inherited Haemophilia A With FVIII Inhibitors High and Low Anamnestic Response.

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.

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.

Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Retention:   Samples Without DNA
Description:

plasma samples

Non-Probability Sample

Patients with moderate or severe hemophilia A with inhibitors divided into two groups:

  1. Patients with inhibitors to FVIII and low anamnestic response: Low responders cohort
  2. Patients with inhibitors to FVIII and high anamnestic response: High responders cohort
Severe Hemophilia A With Inhibitor
Other: TGA (Thrombin generation Assay)
TGA will be performed on plasma in order to evaluate differences in the ability to stimulate the thrombin generation among the different class of FVIII concentrates and possibly identify the "most effective". The TGA will be quarterly repeated in order to verify if it is also adequate to check the therapy effectiveness during the study period
  • LOW RESPONDERS
    Documented low anamnestic response after FVIII exposure (FVIII inhibitors titre >0.6 and < 5 BU/ml tested by Bethesda assay, Nijmegen modification). 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)
    Intervention: Other: TGA (Thrombin generation Assay)
  • HIGH RESPONDERS
    Patients who documented high response after FVIII exposure (FVIII inhibitors titre > 5 BU/ml tested by Bethesda assay, Nijmegen modification) and who are potential candidates to a first or rescue ITI
    Intervention: Other: TGA (Thrombin generation Assay)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
25
June 2016
December 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
Male
Not Provided
No
Contact: Elena Santagostino, Scientific Coordinator +39 02 55035273 hemophilia_ctr@policlinico.mi.it
Contact: Elisa Mancuso +39 02 55035273 hemophilia_ctr@policlinico.mi.it
Italy
 
NCT01505946
PredicTGA, 373
Yes
Grifols Italia S.p.A
Grifols Italia S.p.A
Thrombinoscope
Principal Investigator: Elena Santagostino, MD, PhD Angelo Bianchi Bonomi" Haemophilia Thrombosis Centre I.R.C.S.S. Maggiore Hospital and University of Milan Via Pace 9, 20122 Milan - Italy
Grifols Italia S.p.A
June 2013

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