Haemophilia BNCT02300519
Thrombin Generation Numerical Models Validation in Haemophilic Case
An observational study of Haemophilia B and Haemophilia A, run by Centre Hospitalier Universitaire de Saint Etienne at 1 site in France.
Trial summary
Personalized therapy in haemophilia has not been reached yet. Treatment is substitutive and its doses are only based on the levels of deficient factor VIII (for haemophilia A) or IX (for haemophilia B). Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Haemophilia B, Haemophilia A
- What is being tested?
- blood sampling
- How many people
- 40 participants
- Where
- 1 siteFrance
- Study dates
- Mar 2015to Jul 2015
- 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 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Study population: volunteers witch work in CHU Saint-Etienne
Who may be able to join
- Signed consent form
- Age between 18 and 45 years old
- Male
- no smoker
Who cannot join
- other clinical research protocol participation during the 3 months before inclusion
- Personal or familial history of hemorrhagic disease (parents, brothers and sisters
- Personal history of thrombosis (arterial or venous)
- Familial history of thrombosis before 45 years old (parents, brothers and sisters)
- Drug treatments of aspirin or anti-inflammatory type during the week before sampling
- Surgery the month before sampling
- Chronic pathology responsible for inflammatory syndrome
- Infectious episode in course
Trial locations and contacts
1 site in 1 country.
About this study
Personalized therapy in haemophilia has not been reached yet. Treatment is substitutive and its doses are only based on the levels of deficient factor VIII (for haemophilia A) or IX (for haemophilia B). The bleeding severity is not only related to the factor deficiency but also to levels of other coagulation factors (e.g. factor X, II, AT or TFPI). It's necessary to take them into account in order to individualize treatments; and Thrombin Generation Assay (TGA) with the CAT method (Calibrated Automated Thrombography) is a good way because it measures the result of the coagulation cascade. TGA on Platelet Rich Plasma (PRP) is even closer to physiological conditions than on Platelet Poor Plasma (PPP) because platelet influence is represented. It has already been shown (at least in PPP) that the bleeding tendency in haemophilic patients is usually well correlated to TG. Some TG parameters are used to characterize the individual coagulation phenotype, the most important being the Endogenous Thrombin Potential (ETP) and the Lag Time (LT). A hemorrhagic profile usually provides a longer lag time and / or a lower ETP. However, only few studies tried to determine the influence of each coagulation factor and inhibitor on TG. They were done on Platelet Poor Plasma (PPP) or on lyophilized plasma. So the relation between coagulation factors and the different TG parameters remains to be determined, especially in the haemophilic case. It is possible, experimentally, to find the optimal dose of the factor to be added by measuring TG in samples with different factor VIII or IX concentrations, but this method would be time consuming and expensive, especially because it should be done for each haemophilic patient. A better way consists in using TG numerical models. For a set of initial factor levels they simulate the TG and its associated parameters. It is now essential to validate the existing models, especially in haemophilic cases, in order to see whether they are reliable and can be used in clinical practice afterwards.The objective of this study is to validate thrombin generation numerical models which could predict the factor VIII or IX activity correction to reach a thrombin generation sufficient to avoid bleeding. A comparison between the TG observed in haemophilic patients and the TG predicted by the models is needed to validate the models. In order to define a 'safe' TG i.e. sufficient to avoid bleeding, normal ranges of TG parameters have to be measured.
- Conditions
- Haemophilia B, Haemophilia A
- Being tested
- blood sampling
- Keywords
- Haemophilia, numerical models, thrombin generation, volunteers, endogenous thrombin potential
- Medical subject headings
- Hemophilia B, Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood samplingOther
Samplings will be taken on 4 citrated S-monovette tubes, 3 citrated tubes and 1 EDTA tube, namely 36.5 ml for each volunteer
| Study group | Role | What they receive |
|---|---|---|
| Volunteers | Blood sampling : 1 blood punction of 36.5 ml for each volunteer Receives: Other: blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Endogenous Thrombin Potential (ETP) predicted by numerical models
ETP (i.e. the aera under the thrombin generation curve, nM.min) measured in haemophilic patients is compared to ETP predicted by numerical models.
Measured: up to 12 monthes
Lag Time of the thrombin generation curve predicted by numerical models
Lag time (min) measured in haemophilic patients is compared to the lag time predicted by numerical models
Measured: up to 12 monthes
Peak value of the thrombin generation curve predicted by numerical models
Peak value (nmol thrombin) measured in haemophilic patients is compared to the peak value predicted by numerical models
Measured: up to 12 monthes
Time to peak (TTP) of the thrombin generation curve predicted by numerical models
TTP (min) measured in haemophilic patients is compared to TTP predicted by numerical models
Measured: up to 12 monthes
Velocity Index (V) of the thrombin generation curve predicted by numerical models
Velocity Index measured in haemophilic patients is compared to TTP predicted by numerical models
Measured: up to 12 monthes
Secondary outcomes (5)
Endogenous Thrombin Potential (ETP) for volunteers
ETP (i.e. the aera under the thrombin generation curve, nM.min) is measured by Thromboplastin Generation Tests (TGTs)
Measured: day 1
Lag Time of the thrombin generation curve for volunteers
Lag time (min) of the thrombin generation curve is measured by Thromboplastin Generation Tests (TGTs)
Measured: day 1
Peak value of the thrombin generation curve for volunteers
Peak value of the thrombin generation curve is measured by Thromboplastin Generation Tests (TGTs)
Measured: day 1
Time to peak (TTP) of the thrombin generation curve for volunteers
TTP of the thrombin generation curve is measured by Thromboplastin Generation Tests (TGTs)
Measured: day 1
Velocity Index (V) of the thrombin generation curve for volunteers
Velocity Index (V) of the thrombin generation curves measured by Thromboplastin Generation Tests (TGTs)
Measured: day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2014 (estimated)
- Study startMar 2015
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Haemophilia BStudies 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
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Saint Etienne
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer, Saint Etienne School of Mine
- Responsible party
- Sponsor
- Investigators
- Brigitte TARDY-PONCET, MD, Principal investigator, Centre Hospitalier Universitaire de Saint Etienne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02300519
- Sponsor's protocol ID
- 1408185
- Other IDs
- 2014-A01734-43
- Status last verified
- Aug 2015
- First submitted
- 18 Nov 2014
- Last updated
- 13 Aug 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Thrombin Generation Numerical Models Validation in Haemophilic Case
- ClinicalTrials.gov ID
- NCT02300519
- Acronym / sponsor ID
- 1408185
- Conditions
- Haemophilia B, Haemophilia A
- Keywords
- Haemophilia, numerical models, thrombin generation, volunteers, endogenous thrombin potential
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de Saint EtienneUniversity, hospital or other
- Collaborators
- Pfizer, Saint Etienne School of Mine
- Study start
- Mar 2015
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 25 Nov 2014 (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.
Personalized therapy in haemophilia has not been reached yet. Treatment is substitutive and its doses are only based on the levels of deficient factor VIII (for haemophilia A) or IX (for haemophilia B). The bleeding severity is not only related to the factor deficiency but also to levels of other coagulation factors (e.g. factor X, II, AT or TFPI). It's necessary to take them into account in order to individualize treatments; and Thrombin Generation Assay (TGA) with the CAT method (Calibrated Automated Thrombography) is a good way because it measures the result of the coagulation cascade. TGA on Platelet Rich Plasma (PRP) is even closer to physiological conditions than on Platelet Poor Plasma (PPP) because platelet influence is represented. It has already been shown (at least in PPP) that the bleeding tendency in haemophilic patients is usually well correlated to TG. Some TG parameters are used to characterize the individual coagulation phenotype, the most important being the Endogenous Thrombin Potential (ETP) and the Lag Time (LT). A hemorrhagic profile usually provides a longer lag time and / or a lower ETP. However, only few studies tried to determine the influence of each coagulation factor and inhibitor on TG. They were done on Platelet Poor Plasma (PPP) or on lyophilized plasma. So the relation between coagulation factors and the different TG parameters remains to be determined, especially in the haemophilic case. It is possible, experimentally, to find the optimal dose of the factor to be added by measuring TG in samples with different factor VIII or IX concentrations, but this method would be time consuming and expensive, especially because it should be done for each haemophilic patient. A better way consists in using TG numerical models. For a set of initial factor levels they simulate the TG and its associated parameters. It is now essential to validate the existing models, especially in haemophilic cases, in order to see whether they are reliable and can be used in clinical practice afterwards.The objective of this study is to validate thrombin generation numerical models which could predict the factor VIII or IX activity correction to reach a thrombin generation sufficient to avoid bleeding. A comparison between the TG observed in haemophilic patients and the TG predicted by the models is needed to validate the models. In order to define a 'safe' TG i.e. sufficient to avoid bleeding, normal ranges of TG parameters have to be measured.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Volunteers | – | Other: blood samplingBlood sampling : 1 blood punction of 36.5 ml for each volunteer |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- volunteers witch work in CHU Saint-Etienne
Key inclusion criteria (4 listed)
- Signed consent form
- Age between 18 and 45 years old
- Male
- no smoker
Key exclusion criteria (8 listed)
- other clinical research protocol participation during the 3 months before inclusion
- Personal or familial history of hemorrhagic disease (parents, brothers and sisters
- Personal history of thrombosis (arterial or venous)
- Familial history of thrombosis before 45 years old (parents, brothers and sisters)
- Drug treatments of aspirin or anti-inflammatory type during the week before sampling
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| blood samplingSamplings will be taken on 4 citrated S-monovette tubes, 3 citrated tubes and 1 EDTA tube, namely 36.5 ml for each volunteer | Other | Volunteers |
Primary outcome
Endogenous Thrombin Potential (ETP) predicted by numerical models
Time frame: up to 12 monthes
ETP (i.e. the aera under the thrombin generation curve, nM.min) measured in haemophilic patients is compared to ETP predicted by numerical models.
Lag Time of the thrombin generation curve predicted by numerical models
Time frame: up to 12 monthes
Lag time (min) measured in haemophilic patients is compared to the lag time predicted by numerical models
Peak value of the thrombin generation curve predicted by numerical models
Time frame: up to 12 monthes
Peak value (nmol thrombin) measured in haemophilic patients is compared to the peak value predicted by numerical models
Time to peak (TTP) of the thrombin generation curve predicted by numerical models
Time frame: up to 12 monthes
TTP (min) measured in haemophilic patients is compared to TTP predicted by numerical models
Velocity Index (V) of the thrombin generation curve predicted by numerical models
Time frame: up to 12 monthes
Velocity Index measured in haemophilic patients is compared to TTP predicted by numerical models
5 secondary outcomes
Endogenous Thrombin Potential (ETP) for volunteers
Time frame: day 1
Lag Time of the thrombin generation curve for volunteers
Time frame: day 1
Peak value of the thrombin generation curve for volunteers
Time frame: day 1
Time to peak (TTP) of the thrombin generation curve for volunteers
Time frame: day 1
Velocity Index (V) of the thrombin generation curve for volunteers
Time frame: day 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2015.
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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.
Brigitte TARDY-PONCET, MD principal investigator
Centre Hospitalier Universitaire de Saint Etienne
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Haemophilia B and Haemophilia A, run by Centre Hospitalier Universitaire de Saint Etienne at 1 site in France.
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 4 inclusion and 8 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: finished, as of the sponsor's last update on 13 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Endogenous Thrombin Potential (ETP) predicted by numerical models (time frame: up to 12 monthes). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Aug 2015.