HaemophiliaThrombusNCT01856751
Use of a TGA and TEM in the Assessment of the Efficacy of Treatment With APCC or rFVIIa
An observational study of Haemophilia, run by Stowarzyszenie Pomocy Chorym na Zakrzepicę i Skazy Krwotoczne Thrombus at 6 sites in Poland.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Haemophilia
- How many people
- 80 participants
- Where
- 6 sitesPoland
- Study dates
- Apr 2014to 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 60 patients with acquired haemophilia 20 patients with congenital haemophilia A with inhibitor
Who may be able to join
- patients with acquired haemophilia
- patients with congenital haemophilia A with inhibitor
Who cannot join
None listed.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Poland6 sites, 6 recruiting
- Recruiting
Katedra i Klinika Hematologii i Transplantologii Gdanski Uniwersytet Medyczny
Gdansk, 80-952
Andrzej Mital, MD, PhD
- Recruiting
Szpital Uniwersytecki w Krakowie, Oddzial Kliniczny Alergii i Immunologii
Krakow, 31-501
Jacek Musial, MD, PhD
- Recruiting
Klinika Hematologii Uniwersytetu Medycznego w Lodzi Wojewodzki Szpital Specjalistyczny im. M. Kopernika
Lodz, 93-510
Krzysztof Chojnowski, MD, PhD
- Recruiting
Centrum Diagnostyczno - Lecznicze INTERLAB
Poznan, 61-505
Krystyna Zawilska, MD,PhD
- Recruiting
Instytut Hematologii i Transfuzjologii w Warszawie
Warsaw, 02-776
Jerzy Windyga, MD, PhD
- Recruiting
Katedra i Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku, Akademia Medyczna
Wroclaw, 50-367
Maria Podolak-Dawidziak, MD, PhD
About this study
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
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.
Read more
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.
Read the detailed description
This section is Not applicable
- Conditions
- Haemophilia
- Keywords
- Haemophilia, TGA, TEM
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| haemophilia | Patients with acquired haemophilia. Patients with haemophilia A with inhibitor. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2013 (estimated)
- Study startApr 2014
- Primary completionApr 2016 (estimated)
- Study completionJun 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HaemophiliaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stowarzyszenie Pomocy Chorym na Zakrzepicę i Skazy Krwotoczne Thrombus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Krystyna Zawilska, MD, PhD, Principal investigator, Centrum Diagnostyczno - Lecznicze INTERLABMaria Podolak-Dawidziak, MD,PhD, Principal investigator, Katedra i Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku, Akademia MedycznaAndrzej Mital, MD, PhD, Principal investigator, Katedra i Klinika Hematologii i Transplantologii Gdanski Uniwersytet MedycznyJerzy Windyga, MD, PhD, Principal investigator, Instytut Hematologii i Transfuzjologii w WarszawieKrzysztof Chojnowski, MD, PhD, Principal investigator, Klinika Hematologii Uniwersytetu Medycznego w Lodzi Wojewodzki Szpital Specjalistyczny im. M. KopernikaJacek Musial, MD, PhD, Principal investigator, Szpital Uniwersytecki w Krakowie, Oddzial Kliniczny Alergii i Immunologii
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01856751
- Sponsor's protocol ID
- TGA-TEM
- Acronym
- Thrombus
- Status last verified
- Dec 2015
- First submitted
- 14 May 2013
- Last updated
- 18 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 19719549Berntorp 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.
PubMed 19016901Dargaud 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.
PubMed 18544431Livnat 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.
PubMed 18371162
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01856751
- Acronym / sponsor ID
- Thrombus / TGA-TEM
- Conditions
- Haemophilia
- Keywords
- Haemophilia, TGA, TEM
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Stowarzyszenie Pomocy Chorym na Zakrzepicę i Skazy Krwotoczne ThrombusUniversity, hospital or other
- Study start
- Apr 2014
- Primary completion
- Apr 2016 (estimated)
- Study completion
- Jun 2016 (estimated)
- First posted
- 17 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| haemophilia | – | –Patients with acquired haemophilia. Patients with haemophilia A with inhibitor. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 60 patients with acquired haemophilia 20 patients with congenital haemophilia A with inhibitor
Key inclusion criteria (2 listed)
- patients with acquired haemophilia
- patients with congenital haemophilia A with inhibitor
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Assessment of patient's individual response to therapy with by-passing agents by simultaneous use of TGA and TEM methods.
Time frame: 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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2015.
- Background: PubMed 19719549Dargaud 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.
- Background: PubMed 19016901Berntorp 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.
- Background: PubMed 18544431Dargaud 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.
- Background: PubMed 18371162Livnat 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Krystyna Zawilska, MD, PhD principal investigator
Centrum Diagnostyczno - Lecznicze INTERLAB
Maria Podolak-Dawidziak, MD,PhD principal investigator
Katedra i Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku, Akademia Medyczna
Andrzej Mital, MD, PhD principal investigator
Katedra i Klinika Hematologii i Transplantologii Gdanski Uniwersytet Medyczny
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Haemophilia, run by Stowarzyszenie Pomocy Chorym na Zakrzepicę i Skazy Krwotoczne Thrombus at 6 sites in Poland.
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 2 inclusion and 0 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 18 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Poland. 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 Krystyna M Zawilska, MD, PhD (48618333949, k.zawilska@interia.pl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of patient's individual response to therapy with by-passing agents by simultaneous use of TGA and TEM methods. (time frame: 48 hours). 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 NCT01856751, which also lists 4 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 18 Dec 2015; AzTrials last refreshed its copy on 7 Nov 2026.