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

NCT01856751 | Unknown

• 1 other identifier: TGA-TEM
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 6

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.

Conditions

Haemophilia

Keywords

Haemophilia; TGA; TEM

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

haemophilia

Patients with acquired haemophilia. Patients with haemophilia A with inhibitor.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

60 patients with acquired haemophilia 20 patients with congenital haemophilia A with inhibitor

You may qualify if:

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

Sponsors & Collaborators

• Stowarzyszenie Pomocy Chorym na Zakrzepicę i Skazy Krwotoczne Thrombus: lead

Study Sites (6)

Katedra i Klinika Hematologii i Transplantologii Gdanski Uniwersytet Medyczny

Gdansk, 80-952, Poland

RECRUITING

Szpital Uniwersytecki w Krakowie, Oddzial Kliniczny Alergii i Immunologii

Krakow, 31-501, Poland

RECRUITING

Klinika Hematologii Uniwersytetu Medycznego w Lodzi Wojewodzki Szpital Specjalistyczny im. M. Kopernika

Lodz, 93-510, Poland

RECRUITING

Centrum Diagnostyczno - Lecznicze INTERLAB

Poznan, 61-505, Poland

RECRUITING

Instytut Hematologii i Transfuzjologii w Warszawie

Warsaw, 02-776, Poland

RECRUITING

Katedra i Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku, Akademia Medyczna

Wroclaw, 50-367, Poland

RECRUITING

Related Publications (4)

• 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.

  PMID: 19719549 BACKGROUND

• 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.

  PMID: 19016901 BACKGROUND

• 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.

  PMID: 18544431 BACKGROUND

• 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.

  PMID: 18371162 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

this data is not applicable

MeSH Terms

Conditions

Hemophilia A

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Krystyna Zawilska, MD, PhD

  Centrum Diagnostyczno - Lecznicze INTERLAB

  PRINCIPAL INVESTIGATOR

• Maria Podolak-Dawidziak, MD,PhD

  Katedra i Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku, Akademia Medyczna

  PRINCIPAL INVESTIGATOR

• Andrzej Mital, MD, PhD

  Katedra i Klinika Hematologii i Transplantologii Gdanski Uniwersytet Medyczny

  PRINCIPAL INVESTIGATOR

• Jerzy Windyga, MD, PhD

  Instytut Hematologii i Transfuzjologii w Warszawie

  PRINCIPAL INVESTIGATOR

• Krzysztof Chojnowski, MD, PhD

  Klinika Hematologii Uniwersytetu Medycznego w Lodzi Wojewodzki Szpital Specjalistyczny im. M. Kopernika

  PRINCIPAL INVESTIGATOR

• Jacek Musial, MD, PhD

  Szpital Uniwersytecki w Krakowie, Oddzial Kliniczny Alergii i Immunologii

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Krystyna M Zawilska, MD, PhD

CONTACT

48618333949; k.zawilska@interia.pl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2013
• First Posted: May 17, 2013
• Study Start: April 1, 2014
• Primary Completion: April 1, 2016
• Study Completion: June 1, 2016
• Last Updated: December 18, 2015

Record last verified: 2015-12

Locations

PL (6)