Thrombin Generation Numerical Models Validation in Haemophilic Case

NCT02300519 | Completed

• 2 other identifiers: 14081852014-A01734-43
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

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

Keywords

Haemophilia; numerical models; thrombin generation; volunteers; endogenous thrombin potential

Outcome Measures

Primary Outcomes (5)

• 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

• 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

• 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

• 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

• 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

Secondary Outcomes (5)

• Endogenous Thrombin Potential (ETP) for volunteers

  day 1

• Lag Time of the thrombin generation curve for volunteers

  day 1

• Peak value of the thrombin generation curve for volunteers

  day 1

• Time to peak (TTP) of the thrombin generation curve for volunteers

  day 1

• Velocity Index (V) of the thrombin generation curve for volunteers

  day 1

Study Arms (1)

Volunteers

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

Other: blood sampling

Interventions

blood sampling 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

Volunteers

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

volunteers witch work in CHU Saint-Etienne

You may qualify if:

• Signed consent form
• Age between 18 and 45 years old
• Male
• no smoker

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Saint Etienne: lead
• Pfizer: collaborator
• Saint Etienne School of Mine: collaborator

Study Sites (1)

Chu Saint-Etienne

Saint-Etienne, 42055, France

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

blood

MeSH Terms

Conditions

Hemophilia B; Hemophilia A

Interventions

Blood Specimen Collection

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; Genetic Diseases, X-Linked

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Brigitte TARDY-PONCET, MD

  CHU SAINT-ETIENNE

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 18, 2014
• First Posted: November 25, 2014
• Study Start: March 1, 2015
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: August 13, 2015

Record last verified: 2015-08

Locations

FR (1)