Thrombin Generation Numerical Models Validation in Haemophilic Case

Haemophilia A Clinical Trial

Official title:

Thrombin Generation Numerical Models Validation in Haemophilic Case

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02300519
• Other study ID #: 1408185
• Secondary ID: 2014-A01734-43
• Status: Completed
• Phase: N/A
• First received: November 18, 2014
• Last updated: August 12, 2015
• Start date: March 2015
• Est. completion date: July 2015

Study information

• Verified date: August 2015
• Source: Centre Hospitalier Universitaire de Saint Etienne
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Observational

Clinical 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). 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Signed consent form

• Age between 18 and 45 years old

• Male

• no smoker

Exclusion Criteria:

• 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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Haemophilia A
• Haemophilia B
• Hemophilia A
• Hemophilia B

Intervention

Other:
• blood sampling
Samplings will be taken on 4 citrated S-monovette tubes, 3 citrated tubes and 1 EDTA tube, namely 36.5 ml for each volunteer

Locations

Country	Name	City	State
France	Chu Saint-Etienne	Saint-Etienne

Sponsors (3)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Saint Etienne	Ecole Normale Supérieure des Mines de Saint-Etienne, Pfizer

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	up to 12 monthes	No
Primary	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	up to 12 monthes	No
Primary	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	up to 12 monthes	No
Primary	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	up to 12 monthes	No
Primary	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	up to 12 monthes	No
Secondary	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)	day 1	No
Secondary	Lag Time of the thrombin generation curve for volunteers	Lag time (min) of the thrombin generation curve is measured by Thromboplastin Generation Tests (TGTs)	day 1	No
Secondary	Peak value of the thrombin generation curve for volunteers	Peak value of the thrombin generation curve is measured by Thromboplastin Generation Tests (TGTs)	day 1	No
Secondary	Time to peak (TTP) of the thrombin generation curve for volunteers	TTP of the thrombin generation curve is measured by Thromboplastin Generation Tests (TGTs)	day 1	No
Secondary	Velocity Index (V) of the thrombin generation curve for volunteers	Velocity Index (V) of the thrombin generation curves measured by Thromboplastin Generation Tests (TGTs)	day 1	No