AzTrials
AzTrials

Severe Hemophilia A With InhibitorPredicTGANCT01505946

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

An observational study of Severe Hemophilia A With Inhibitor, run by Grifols Italia S.p.A at 15 sites in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Any age, men only
Conditions the study is for
Severe Hemophilia A With Inhibitor
What is being tested?
TGA (Thrombin generation Assay)
How many people
25 participants
Where
15 sitesItaly
Study dates
Mar 2012to Jun 2016
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • Men only
  • No healthy volunteers
  • Child, Adult, Older adult

Study population: 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

Who may be able to join

  • 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)
  • 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

Who cannot join

  • 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

Trial locations and contacts

15 sites in 1 country.

Elena Santagostino, Scientific Coordinator contact

+39 02 55035273

hemophilia_ctr@policlinico.mi.it

Elisa Mancuso contact

+39 02 55035273

hemophilia_ctr@policlinico.mi.it

15 sites in 1 country

Italy15 sites, 10 recruiting

  • Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari

    Bari, Apulia, 70124

    Active, not recruiting

  • UO Angiologia e Malattie della Coagulazione "Marino Golinelli" Az Osp. Policlinico S. Orsola Malpighi

    Bologna, Emilia-Romagna, 40138

    Lelia Valdrè, MD, lvaldre@aosp.bo.it

    Gualtiero Palareti, MD

    Recruiting

  • Ospedale Civile dell' Annunziata

    Cosenza, Calabria, 87100

    Filomena Daniele, MD, fildaniele@libero.it

    Filomena Daniele, MD

    Recruiting

  • Agenzia per l'Emofilia Azienda Ospedaliera Universitaria Careggi

    Florence, Tuscany, 50134

    Massimo Morfini, MD, massimo.morfini@unfi.it

    Massimo Morfini, MD

    Recruiting

  • Az. Universitaria Policlinico "Federico II" Dip. Assist. di Clinica Medica

    Naples, Campania, 80131

    Active, not recruiting

  • Az. Ospedaliera di Padova, Clinica Medica IIa

    Padua, Veneto, 35128

    Ezio Zanon, MD, ezio.zanon@unipd.it

    Ezio Zanon, MD

    Recruiting

  • Centro di Riferimento Emostasi e Trombosi in età pediatrica Ospedale dei bambini G. Di Cristina

    Palermo, Palermo

    Fabio Gagliano, Physician, ematopediatriaob@teletu.it

    Fabio Gagliano, Dr.

    Recruiting

  • Ematologia Dipartimento di Biotecnologie Cellulari Università La Sapienza - Policlinico Umberto I

    Rome, Lazio, 00161

    Active, not recruiting

  • Ospedale Pediatrico Bambino Gesù di Roma

    Rome, Lazio, 00165

    Matteo Luciani, MD, matteo.luciani@opbg.net

    Matteo Luciani, MD

    Recruiting

  • Università Cattolica - Policlinico A. Gemelli

    Rome, Lazio, 00168

    Active, not recruiting

  • Azienda Ospedialiera Ospedale Infantile Regina Margherita - S.Anna

    Turin, Piedmont, 10126

    Maria Messina, MD, maria.messina@oirmsantanna.piemonte.it

    Maria Messina, MD

    Recruiting

  • Ospedale Le Molinette "S. G. Battista"

    Turin, Piedmont, 10126

    Alessandra Borchiellini, MD, aborchiellini@molinette.piemonte.it

    Alessandra Borchiellini, MD

    Recruiting

  • Azienda Ospedaliera "Santa Maria della Misericordia"

    Udine, Friuli Venezia Giulia, 33100

    Giovanni Barillari, MD, barillari.giovanni@aoud.sanita.fvg.it

    Giovanni Barillari, MD

    Recruiting

  • Azienda Ospedaliera Univesitaria Integrata di Verona - Borgo Roma

    Verona, Veneto, 37126

    Active, not recruiting

  • Dipartimento di Terapie Cellulari ed Ematologia Ospedale San Bortolo

    Vicenza, Veneto, 36100

    Giancarlo Castaman, MD

    Giancarlo Castaman, MD

    Recruiting

Other trials in Italy

About this study

Official title: 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.

Read the 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.

Being tested
TGA (Thrombin generation Assay)
Keywords
Thrombin, Hemophilia, Inhibitors, Immunotolerance, Haemostatic, FVIII, Epitopes, Moderately severe Hemophilia A with inhibitor
Medical subject headings
Hemophilia A

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TGA (Thrombin generation Assay)Other

    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

Study groups in NCT01505946
Study groupRoleWhat they receive
LOW RESPONDERSDocumented 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)
Receives: Other: TGA (Thrombin generation Assay)
HIGH RESPONDERSPatients 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
Receives: Other: TGA (Thrombin generation Assay)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Thrombin generation result

    Thrombin generation results of the TGA applied on plasma patients whith inhibitor matched with different class of FVIII concentrate

    Measured: 12 months

Secondary outcomes (6)

  1. Epitope mapping results

    epitope mapping test on the plasma patient during the therapy for a follow-up period of 12 month

    Measured: 12 months

  2. Incidence of all breakthrough (BT) bleedings

    events/month

    Measured: 12 months

  3. Total FVIII dose required to treat the patients

    (IU/year)

    Measured: 12 months

  4. the inhibitor titre course

    Measured: 12 months

  5. Use of bypassing agents

    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)

    Measured: 12 months

  6. ITI outcome only for patient under this kind of treatment

    % 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)

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jan 2012 (estimated)
  2. Study startMar 2012
  3. Primary completionDec 2015 (estimated)
  4. Study completionJun 2016 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
25 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01505946
Sponsor's protocol ID
PredicTGA
Other IDs
373
Acronym
PredicTGA
Status last verified
Jun 2013
First submitted
5 Jan 2012
Last updated
17 Jun 2013
Results posted
No
Data monitoring committee
Yes

Publications

  • Wight J, Paisley S. The epidemiology of inhibitors in haemophilia A: a systematic review. Haemophilia. 2003 Jul;9(4):418-35. doi: 10.1046/j.1365-2516.2003.00780.x.

    PubMed 12828678

  • Salvagno GL, Astermark J, Ekman M, Franchini M, Guidi GC, Lippi G, Poli G, Berntorp E. Impact of different inhibitor reactivities with commercial factor VIII concentrates on thrombin generation. Haemophilia. 2007 Jan;13(1):51-6. doi: 10.1111/j.1365-2516.2006.01400.x.

    PubMed 17212725

  • Iorio A, Halimeh S, Holzhauer S, Goldenberg N, Marchesini E, Marcucci M, Young G, Bidlingmaier C, Brandao LR, Ettingshausen CE, Gringeri A, Kenet G, Knofler R, Kreuz W, Kurnik K, Manner D, Santagostino E, Mannucci PM, Nowak-Gottl U. Rate of inhibitor development in previously untreated hemophilia A patients treated with plasma-derived or recombinant factor VIII concentrates: a systematic review. J Thromb Haemost. 2010 Jun;8(6):1256-65. doi: 10.1111/j.1538-7836.2010.03823.x. Epub 2010 Mar 17.

    PubMed 20345722

  • Astermark J, Santagostino E, Keith Hoots W. Clinical issues in inhibitors. Haemophilia. 2010 Jul;16 Suppl 5:54-60. doi: 10.1111/j.1365-2516.2010.02294.x.

    PubMed 20590857

  • Gringeri A, Mantovani LG, Scalone L, Mannucci PM; COCIS Study Group. Cost of care and quality of life for patients with hemophilia complicated by inhibitors: the COCIS Study Group. Blood. 2003 Oct 1;102(7):2358-63. doi: 10.1182/blood-2003-03-0941. Epub 2003 Jun 19.

    PubMed 12816859

  • Kopecky EM, Greinstetter S, Pabinger I, Buchacher A, Romisch J, Jungbauer A. Mapping of FVIII inhibitor epitopes using cellulose-bound synthetic peptide arrays. J Immunol Methods. 2006 Jan 20;308(1-2):90-100. doi: 10.1016/j.jim.2005.10.016. Epub 2005 Dec 5.

    PubMed 16376372

  • Chambost H. Assessing risk factors: prevention of inhibitors in haemophilia. Haemophilia. 2010 Mar;16 Suppl 2:10-5. doi: 10.1111/j.1365-2516.2009.02197.x.

    PubMed 20132333

  • Boekhorst J, Lari GR, D'Oiron R, Costa JM, Novakova IR, Ala FA, Lavergne JM, VAN Heerde WL. Factor VIII genotype and inhibitor development in patients with haemophilia A: highest risk in patients with splice site mutations. Haemophilia. 2008 Jul;14(4):729-35. doi: 10.1111/j.1365-2516.2008.01694.x. Epub 2008 May 12.

    PubMed 18503540

  • Coppola A, Margaglione M, Santagostino E, Rocino A, Grandone E, Mannucci PM, Di Minno G; AICE PROFIT Study Group. Factor VIII gene (F8) mutations as predictors of outcome in immune tolerance induction of hemophilia A patients with high-responding inhibitors. J Thromb Haemost. 2009 Nov;7(11):1809-15. doi: 10.1111/j.1538-7836.2009.03615.x. Epub 2009 Sep 9.

    PubMed 19740093

  • Kallas A, Talpsep T. von Willebrand factor in factor VIII concentrates protects against neutralization by factor VIII antibodies of haemophilia A patients. Haemophilia. 2001 Jul;7(4):375-80. doi: 10.1046/j.1365-2516.2001.00530.x.

    PubMed 11442642

  • Astermark J, Voorberg J, Lenk H, DiMichele D, Shapiro A, Tjonnfjord G, Berntorp E. Impact of inhibitor epitope profile on the neutralizing effect against plasma-derived and recombinant factor VIII concentrates in vitro. Haemophilia. 2003 Sep;9(5):567-72. doi: 10.1046/j.1365-2516.2003.00802.x.

    PubMed 14511295

  • Berntorp E. Variation in factor VIII inhibitor reactivity with different commercial factor VIII preparations: is it of clinical importance? Haematologica. 2003 Jun;88(6):EREP03.

    PubMed 12826529

  • Gringeri A. VWF/FVIII concentrates in high-risk immunotolerance: the RESIST study. Haemophilia. 2007 Dec;13 Suppl 5:73-7. doi: 10.1111/j.1365-2516.2007.01579.x.

    PubMed 18078402

  • Goudemand J, Rothschild C, Demiguel V, Vinciguerrat C, Lambert T, Chambost H, Borel-Derlon A, Claeyssens S, Laurian Y, Calvez T; FVIII-LFB and Recombinant FVIII study groups. Influence of the type of factor VIII concentrate on the incidence of factor VIII inhibitors in previously untreated patients with severe hemophilia A. Blood. 2006 Jan 1;107(1):46-51. doi: 10.1182/blood-2005-04-1371. Epub 2005 Sep 15.

    PubMed 16166584

  • Gringeri A, Monzini M, Tagariello G, Scaraggi FA, Mannucci PM; Emoclot15 Study Members. Occurrence of inhibitors in previously untreated or minimally treated patients with haemophilia A after exposure to a plasma-derived solvent-detergent factor VIII concentrate. Haemophilia. 2006 Mar;12(2):128-32. doi: 10.1111/j.1365-2516.2006.01201.x.

    PubMed 16476086

Questions about this trial

What is this clinical trial studying?

An observational study of Severe Hemophilia A With Inhibitor, run by Grifols Italia S.p.A at 15 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 17 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Elena Santagostino, Scientific Coordinator (+39 02 55035273, hemophilia_ctr@policlinico.mi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Thrombin generation result (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01505946, which also lists 18 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2013.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in