Use of a TGA and TEM in the Assessment of the Efficacy of Treatment With APCC or rFVIIa

Haemophilia Clinical Trial

— Thrombus  

Official title:

Use of a TGA and TEM in the Assessment of the Efficacy of Treatment With APCC or rFVIIa Concentrate in Patients With Acquired Haemophilia and in Patients With Haemophilia A With Inhibitors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01856751
• Other study ID #: TGA-TEM
• Status: Recruiting
• Phase: N/A
• First received: May 14, 2013
• Last updated: December 17, 2015
• Start date: April 2014
• Est. completion date: June 2016

Study information

• Verified date: December 2015
• Source: Stowarzyszenie Pomocy Chorym na Zakrzepice i Skazy Krwotoczne Thrombus
• Contact: Krystyna M Zawilska, MD, PhD
• Phone: 48618333949
• Email: k.zawilska[@]interia.pl
• Is FDA regulated: No
• Health authority: Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
• Study type: Observational

Clinical Trial Summary

Occurrence of inhibitors to coagulation factor VIII is diagnosed in ~30% patients with haemophilia A. Presence of inhibitor with a titre >5 BU/ml requires the use of by-passing agents: recombinant activated Factor VIIa concentrate (rFVIIa) and/or activated prothrombin complex concentrate (APCC). Similarly, haemorrhagic complications in patients with acquired haemophilia and inhibitor titre >5 BU/ml should be treated with by-passing agents.

Response to treatment with by-passing agents is patient-specific, and can vary in the same patient during subsequent bleedings. Some patients have good response to both products, however in other patients a better bleeding control is provided by one of the mentioned above agents (APCC or rFVIIa). There are clinical situations when severe bleedings requires an alternate use of both these agents.

Traditional methods of laboratory tests used post-treatment in patients with haemophilia without inhibitors are useless in the presence of inhibitor. Laboratory monitoring of therapy with by-passing agents is possible with the use of global tests for the coagulation process assessment, which are as follows: thrombin generation assay (TGA) and thromboelastometry (TEM).

Several studies revealed that TGA allows a monitoring of therapy with by-passing agents in patients with haemophilia A and inhibitor - the choice of the most effective treatment option - agent type and its dose, as well as laboratory assessment of treatment efficacy.

Up to date, laboratory tests assessing the efficacy of by-passing agents in patients with acquired haemophilia were not conducted.

In Factor VIII or IX deficiency conditions, fibrin's fibres generated by thrombin are morphologically thicker, and blood clots have increased susceptibility to fibrinolytic enzymes. Blood clot stability may be assessed with the use of thromboelastometry (TEM). We can hypothesize that simultaneous use of TGA and TEM methods may allow for an assessment of patient's individual response to therapy with by-passing agents. Clinical significance of the minimal dose of APCC and rFVIIa, needed to TGA and TEM normalization, requires further studies.

Tests' purpose: Examination of the hypothesis that simultaneous use of thrombin generation assay (TGA) and thromboelastometry (TEM) may facilitate the choice of optimal therapy with by-passing agents and laboratory monitoring of efficacy of those agents in patients with acquired haemophilia or haemophilia A with inhibitor.

Description:

This section is Not applicable

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: June 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• patients with acquired haemophilia

• patients with congenital haemophilia A with inhibitor

Exclusion Criteria:

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Haemophilia
• Hemophilia A

Locations

Country	Name	City	State
Poland	Katedra i Klinika Hematologii i Transplantologii Gdanski Uniwersytet Medyczny	Gdansk
Poland	Szpital Uniwersytecki w Krakowie, Oddzial Kliniczny Alergii i Immunologii	Krakow
Poland	Klinika Hematologii Uniwersytetu Medycznego w Lodzi Wojewodzki Szpital Specjalistyczny im. M. Kopernika	Lodz
Poland	Centrum Diagnostyczno - Lecznicze INTERLAB	Poznan
Poland	Instytut Hematologii i Transfuzjologii w Warszawie	Warszawa
Poland	Katedra i Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku, Akademia Medyczna	Wroclaw

Sponsors (1)

Lead Sponsor	Collaborator
Stowarzyszenie Pomocy Chorym na Zakrzepice i Skazy Krwotoczne Thrombus

Country where clinical trial is conducted

Poland, 

References & Publications (4)

Berntorp E. Differential response to bypassing agents complicates treatment in patients with haemophilia and inhibitors. Haemophilia. 2009 Jan;15(1):3-10. doi: 10.1111/j.1365-2516.2008.01931.x. Epub 2008 Nov 10. Review. — View Citation

Dargaud Y, Bordet JC, Lienhart A, Negrier C. Use of the thrombin generation test to evaluate response to treatment with recombinant activated factor VII. Semin Hematol. 2008 Apr;45(2 Suppl 1):S72-3. doi: 10.1053/j.seminhematol.2008.03.008. — View Citation

Dargaud Y, Negrier C. Thrombin generation testing in haemophilia comprehensive care centres. Haemophilia. 2010 Mar;16(2):223-30. doi: 10.1111/j.1365-2516.2009.02082.x. Epub 2009 Aug 27. Review. — View Citation

Livnat T, Martinowitz U, Zivelin A, Seligsohn U. Effects of factor VIII inhibitor bypassing activity (FEIBA), recombinant factor VIIa or both on thrombin generation in normal and haemophilia A plasma. Haemophilia. 2008 Jul;14(4):782-6. doi: 10.1111/j.1365-2516.2008.01688.x. Epub 2008 Mar 21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of patient's individual response to therapy with by-passing agents by simultaneous use of TGA and TEM methods.	This is non-inverventional study as the protocol will not assign specific treatment to the particular subjects of the study. Patients will be treated with APCC or rFVIIa based on the experience of the study site. Patients are prescribed a treatment according to their physician's judgement or local clinical practice. This is observation of the everyday clinical practise on site.	48 hours	No