Clinical trial NCT01856751: Use of a TGA and TEM in the Assessment of the Efficacy of Treatment With APCC or rFVIIa
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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Haemophilia
Keywords: Haemophilia
TGA
TEM
Lead sponsor: Stowarzyszenie Pomocy Chorym na Zakrzepicę i Skazy Krwotoczne Thrombus
Sponsor class: OTHER
First posted: 2013-05-17
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 60 patients with acquired haemophilia 20 patients with congenital haemophilia A with inhibitor

Brief 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.

Detailed description: This section is Not applicable

Eligibility criteria: Inclusion Criteria:

* patients with acquired haemophilia
* patients with congenital haemophilia A with inhibitor

Exclusion Criteria:

Primary outcomes:
measure: Assessment of patient's individual response to therapy with by-passing agents by simultaneous use of TGA and TEM methods.
timeFrame: 48 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Gdansk
country: Poland
facility: Katedra i Klinika Hematologii i Transplantologii Gdanski Uniwersytet Medyczny
city: Krakow
country: Poland
facility: Szpital Uniwersytecki w Krakowie, Oddzial Kliniczny Alergii i Immunologii
city: Lodz
country: Poland
facility: Klinika Hematologii Uniwersytetu Medycznego w Lodzi Wojewodzki Szpital Specjalistyczny im. M. Kopernika
city: Poznan
country: Poland
facility: Centrum Diagnostyczno - Lecznicze INTERLAB
city: Warszawa
country: Poland
facility: Instytut Hematologii i Transfuzjologii w Warszawie
city: Wroclaw
country: Poland
facility: Katedra i Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku, Akademia Medyczna
Study officials:
affiliation: Centrum Diagnostyczno - Lecznicze INTERLAB
name: Krystyna Zawilska, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Katedra i Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku, Akademia Medyczna
name: Maria Podolak-Dawidziak, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Katedra i Klinika Hematologii i Transplantologii Gdanski Uniwersytet Medyczny
name: Andrzej Mital, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Instytut Hematologii i Transfuzjologii w Warszawie
name: Jerzy Windyga, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Klinika Hematologii Uniwersytetu Medycznego w Lodzi Wojewodzki Szpital Specjalistyczny im. M. Kopernika
name: Krzysztof Chojnowski, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Szpital Uniwersytecki w Krakowie, Oddzial Kliniczny Alergii i Immunologii
name: Jacek Musial, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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. No abstract available.
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.