Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 2 of 6 for:    "Hemophilia" | "HIV Protease Inhibitors"

Tissue Factor Pathway Inhibitor (TFPI) and Haemorrhagic Manifestations in Haemophilia A and B Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02540187
Recruitment Status : Completed
First Posted : September 3, 2015
Last Update Posted : March 10, 2016
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Saint Etienne

Brief Summary:

Haemophilia is a rare and serious congenital defect of blood coagulation due to a genetic mutation on a sexual chromosome. It affects quasi-essentially the men and it is responsible for bleeding. There are two types of haemophilia: Haemophilia A, (85 % of cases), due to a factor VIII (FVIII) deficiency and Haemophilia B (15 % of cases) due to factor IX (FIX) deficiency. According to the intensity of the defect, there are three forms of haemophilia: severe (FVIII or FIX lower than 1 %), moderate (factor level between 1 and 5 %), minor (factor level between 5 and 40 %). For a same level of factor VIII or IX, hemorrhagic manifestations are variable from one patient to the other. Moreover, several studies showed that haemophilic B patients bleed less and consume fewer anti-hemophilic concentrate that haemophilic A patients.

The main inhibitors of the coagulation are antithrombin, Protein C-Protein S-Thrombomodulin system, and tissue factor pathway inhibitor (TFPI). TFPI is the specific and exclusive inhibitor of tissue factor pathway that is the main way by which plasmatic coagulation starts. TFPI is a potent direct inhibitor of factor Xa and Xa-dependent inhibitor of the VIIa-Tissue Factor (TF) complex. In hemophilic patient, the production of Xa by the amplification pathway being strongly altered because of factor VIII or IX deficiency, thrombin generation (via Xa) comes exclusively from TFPI regulated tissue factor pathway. We can thus say that if haemophilic patients bleed, it is also because of the presence of TFPI that inhibits at the same time Xa and the complex TF-VIIa as soon as factor Xa is generated.


Condition or disease Intervention/treatment
Hemophilia Other: blood specimen

Layout table for study information
Study Type : Observational
Actual Enrollment : 164 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Tissue Factor Pathway Inhibitor (TFPI) and Haemorrhagic Manifestations in Haemophilia A and B Patients
Study Start Date : February 2012
Actual Primary Completion Date : February 2016
Actual Study Completion Date : February 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemophilia

Group/Cohort Intervention/treatment
haemophilia A
  1. Blood specimen for measuring :

    • Free TFPI and TFPI activity levels
    • Thrombin generation in platelet rich plasma (PRP) and platelet poor plasma (PPP)
    • Thrombin generation assay (TGA) in fresh PRP and frozen PPP
  2. Hemorrhage score for each patient
Other: blood specimen
Haemophilia B
  1. Blood specimen for measuring :

    • Free TFPI and TFPI activity levels
    • Thrombin generation in platelet rich plasma (PRP) and platelet poor plasma (PPP)
    • Thrombin generation assay (TGA) in fresh PRP and frozen PPP
  2. Hemorrhage score for each patient
Other: blood specimen



Primary Outcome Measures :
  1. Comparison for TFPI level between Haemophilia A and Haemophilia B [ Time Frame: day 1 ]
    Comparison for TFPI level between Haemophilia A and Haemophilia B

  2. Comparison for TFPI level between severe Haemophilia A and severe Haemophilia B [ Time Frame: Day 1 ]
    Comparison for TFPI level between severe Haemophilia A and severe Haemophilia B

  3. Comparison for TFPI level between moderate or mild Haemophilia A and moderate or mild Haemophilia B [ Time Frame: Day 1 ]
    Comparison for TFPI level between moderate or mild Haemophilia A and moderate or mild Haemophilia B


Secondary Outcome Measures :
  1. Correlation between free TFPI and hemorrhagic score [ Time Frame: day 1 ]

    Hemorrhagic score is established on the 5 to 10 last years. For severe hemophilic patients: it will use a composite scoring system designed to reflect the clinical severity of haemophilia and named HSS for Haemophilia Severity Score (HSS). It consists in the sum of three components: annual incidence of joint bleeds, orthopedic joint score and annual factor utilization. The orthopedic joint score combines pain and physical examination scores as recommended by the orthopedic Advisory Committee of the World Federation of Haemophilia.

    For mild or moderate hemophilic patients, HSS is not suitable. A composite measure will be used and consist in all bleeding events and consumption of factor concentrate in surgical situation.

    Free TFPI levels will be measured by ELISA according to the manufacturer's recommendations


  2. Correlation between TFPI activity and hemorrhagic score [ Time Frame: day 1 ]

    Hemorrhagic score is established on the 5 to 10 last years. For severe hemophilic patients: it will use a composite scoring system designed to reflect the clinical severity of haemophilia and named HSS for Haemophilia Severity Score. It consists in the sum of three components: annual incidence of joint bleeds, orthopedic joint score and annual factor utilization. The orthopedic joint score combines pain and physical examination scores as recommended by the orthopedic Advisory Committee of the World Federation of Haemophilia.

    For mild or moderate hemophilic patients, HSS is not suitable. A composite measure will be used and consist in all bleeding events and consumption of factor concentrate in surgical situation.

    TFPI activity will be measured according to the technique described and modified by Sandset


  3. Correlation between Endogenous Thrombin Potential (ETP) and free TFPI [ Time Frame: day 1 ]
    Endogenous Thrombin Potential (i.e. the aera under the thrombin generation curve, nM.min) is measured by thromboplastin Generation Test (TGTs) Free TFPI levels will be measured by ELISA according to the manufacturer's recommendations

  4. Correlation between Lag Time and free TFPI [ Time Frame: day 1 ]
    Lag time (min) of the thrombin Generation curve is measured by thromboplastin Generation Test (TGTs) Free TFPI levels will be measured by ELISA according to the manufacturer's recommendations

  5. Correlation between Peak value and free TFPI [ Time Frame: day 1 ]
    Peak Value (PV, nmol thrombin) of the thrombin Generation curve is measured by thromboplastin Generation Test (TGTs) Free TFPI levels will be measured by ELISA according to the manufacturer's recommendations

  6. Correlation between Time to Peak and free TFPI [ Time Frame: day 1 ]
    Time to Peak (TTP, min) of the thrombin Generation curve is measured by thromboplastin Generation Test (TGTs) Free TFPI levels will be measured by ELISA according to the manufacturer's recommendations

  7. Correlation between ETP and hemorrhagic score [ Time Frame: day 1 ]

    Endogenous Thrombin Potential (i.e. the aera under the thrombin generation curve, nM.min) is measured by Thromboplastin Generation Test (TGTs) Hemorrhagic score is established on the 5 to 10 last years. For severe hemophilic patients: it will use a composite scoring system designed to reflect the clinical severity of haemophilia and named HSS for Haemophilia Severity Score. It consists in the sum of three components: annual incidence of joint bleeds, orthopedic joint score and annual factor utilization. The orthopedic joint score combines pain and physical examination scores as recommended by the orthopedic Advisory Committee of the World Federation of Haemophilia.

    For mild or moderate hemophilic patients, HSS is not suitable. A composite measure will be used and consist in all bleeding events and consumption of factor concentrate in surgical situation.


  8. Correlation between Lag Time and hemorrhagic score [ Time Frame: day 1 ]

    Lag time (min) of the thrombin generation curve is measured by thromboplastin Generation Test (TGTs) Hemorrhagic score is established on the 5 to 10 last years. For severe hemophilic patients: it will use a composite scoring system designed to reflect the clinical severity of haemophilia and named HSS for Haemophilia Severity Score. It consists in the sum of three components: annual incidence of joint bleeds, orthopedic joint score and annual factor utilization. The orthopedic joint score combines pain and physical examination scores as recommended by the orthopedic Advisory Committee of the World Federation of Haemophilia.

    For mild or moderate hemophilic patients, HSS is not suitable. A composite measure will be used and consist in all bleeding events and consumption of factor concentrate in surgical situation.


  9. Correlation between Peak Value and hemorrhagic score [ Time Frame: day 1 ]

    Peak Value (PV, nmol thrombin) of the thrombin generation curve is measured by thromboplastin Generation Test (TGTs) Hemorrhagic score is established on the 5 to 10 last years. For severe hemophilic patients: it will use a composite scoring system designed to reflect the clinical severity of haemophilia and named HSS for Haemophilia Severity Score. It consists in the sum of three components: annual incidence of joint bleeds, orthopedic joint score and annual factor utilization. The orthopedic joint score combines pain and physical examination scores as recommended by the orthopedic Advisory Committee of the World Federation of Haemophilia.

    For mild or moderate hemophilic patients, HSS is not suitable. A composite measure will be used and consist in all bleeding events and consumption of factor concentrate in surgical situation.


  10. Correlation between Time to Peak and hemorrhagic score [ Time Frame: day 1 ]

    Time to Peak (TTP, min) of the thrombin generation curve is measured by thromboplastin Generation Test (TGTs) Hemorrhagic score is established on the 5 to 10 last years. For severe hemophilic patients: it will use a composite scoring system designed to reflect the clinical severity of haemophilia and named HSS for Haemophilia Severity Score. It consists in the sum of three components: annual incidence of joint bleeds, orthopedic joint score and annual factor utilization. The orthopedic joint score combines pain and physical examination scores as recommended by the orthopedic Advisory Committee of the World Federation of Haemophilia.

    For mild or moderate hemophilic patients, HSS is not suitable. A composite measure will be used and consist in all bleeding events and consumption of factor concentrate in surgical situation.


  11. Comparison for ETP between haemophilia A et Haemophilia B [ Time Frame: Day 1 ]
    Endogenous Thrombin Potential (i.e. the aera under the thrombin generation curve, nM.min) is measured by Thromboplastin Generation Test (TGTs)

  12. Comparison for lag time between haemophilia A et Haemophilia B [ Time Frame: Day 1 ]
    Lag time (min) of the thrombin generation curve is measured by thromboplastin Generation Test (TGTs)

  13. Comparison for Peak Value between haemophilia A et Haemophilia B [ Time Frame: Day 1 ]
    Peak Value (PV, nmol thrombin) of the thrombin generation curve is measured by thromboplastin Generation Test (TGTs)

  14. Comparison for Time to Peak between haemophilia A et Haemophilia B [ Time Frame: day 1 ]
    Time to Peak (TTP, min) of the thrombin generation curve is measured by thromboplastin Generation Test (TGTs)


Biospecimen Retention:   Samples Without DNA
blood specimen


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Haemophilia A and B patients between 18 and 65 years old, whatever the severity of their disease
Criteria

Inclusion Criteria:

  • Haemophilia A and B patients between 18 and 65 years old, whatever the severity of their disease, who have signed the informed consent form
  • On-demand or on prophylactic therapy.
  • Regular monitoring in investigator center.

Exclusion Criteria:

  • - Haemophilia patients under 18.
  • Presence of an inhibitor at any time before or during the study period.
  • Patients who received factor VIII concentrate less than 72 hours or factor IX concentrate less than 96 hours before blood collection
  • Patients who refused to sign informed consent
  • Patient data over the last 5 years at least not available.
  • No regular monitoring in haemophilia center (required at least one visit every 18 months for severe or moderate hemophiliac patients).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02540187


Locations
Layout table for location information
France
CHRU Lille
Lille, France
HCL
Lyon, France
AP-HM
Marseille, France
Chu Nancy
Nancy, France
Chu Reims
Reims, France
CHU Saint-Etienne
Saint-Etienne, France, 42055
Chu Tours
Tours, France
Sponsors and Collaborators
Centre Hospitalier Universitaire de Saint Etienne
Pfizer

Layout table for additonal information
Responsible Party: Centre Hospitalier Universitaire de Saint Etienne
ClinicalTrials.gov Identifier: NCT02540187     History of Changes
Other Study ID Numbers: 1108164
First Posted: September 3, 2015    Key Record Dates
Last Update Posted: March 10, 2016
Last Verified: March 2016
Keywords provided by Centre Hospitalier Universitaire de Saint Etienne:
haemophilia
TFPI
thrombin generation
hemorrhagic score
Additional relevant MeSH terms:
Layout table for MeSH terms
Hemophilia A
Protease Inhibitors
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Lipoprotein-associated coagulation inhibitor
Factor VIII
Thrombin
Thromboplastin
Coagulants
Hemostatics
Anticoagulants
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Serine Proteinase Inhibitors
Enzyme Inhibitors
Factor Xa Inhibitors
Antithrombins