Thrombin Generation Numerical Models Validation in Haemophilic Case

NCT ID: NCT02300519

Last Updated: 2015-08-13

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 40 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-03-31
• Study Completion Date: 2015-07-31

Brief 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.

Conditions

Haemophilia B; Haemophilia A

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Volunteers

Blood sampling : 1 blood punction of 36.5 ml for each volunteer

blood sampling

Intervention Type: OTHER

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

Interventions

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

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Saint Etienne School of Mine

OTHER

Sponsor Role: collaborator

Centre Hospitalier Universitaire de Saint Etienne

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brigitte TARDY-PONCET, MD

Role: PRINCIPAL_INVESTIGATOR

CHU SAINT-ETIENNE

Locations

Chu Saint-Etienne

Saint-Etienne, , France

Countries

France

Other Identifiers

2014-A01734-43

Identifier Type: OTHER

Identifier Source: secondary_id

1408185

Identifier Type: -

Identifier Source: org_study_id