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

• Conditions: Haemophilia

• Registration Number: NCT01856751
• Lead Sponsor: Stowarzyszenie Pomocy Chorym na Zakrzepicę i Skazy Krwotoczne Thrombus

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

Study Timeline

• Study First Submitted: 2013-05-14
• Study First Submitted QC: 2013-05-16
• Study First Posted: 2013-05-17
• Study Start: 2014-04
• Status Verified: 2015-12
• Last Update Submitted: 2015-12-17
• Last Update Posted: 2015-12-18
• Primary Completion: 2016-04
• Study Completion: 2016-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• patients with acquired haemophilia
• patients with congenital haemophilia A with inhibitor

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Assessment of patient's individual response to therapy with by-passing agents by simultaneous use of TGA and TEM methods.	48 hours	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.

Trial Locations

Locations (6)

Katedra i Klinika Hematologii i Transplantologii Gdanski Uniwersytet Medyczny; 🇵🇱 Gdansk, Poland

Klinika Hematologii Uniwersytetu Medycznego w Lodzi Wojewodzki Szpital Specjalistyczny im. M. Kopernika; 🇵🇱 Lodz, Poland

Katedra i Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku, Akademia Medyczna; 🇵🇱 Wroclaw, Poland

Szpital Uniwersytecki w Krakowie, Oddzial Kliniczny Alergii i Immunologii; 🇵🇱 Krakow, Poland

Centrum Diagnostyczno - Lecznicze INTERLAB; 🇵🇱 Poznan, Poland

Instytut Hematologii i Transfuzjologii w Warszawie; 🇵🇱 Warszawa, Poland