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Trial record 2 of 6 for:    "Hemophilia" | "HIV Protease Inhibitors"

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

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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

Tracking Information
First Submitted Date September 1, 2015
First Posted Date September 3, 2015
Last Update Posted Date March 10, 2016
Study Start Date February 2012
Actual Primary Completion Date February 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: September 1, 2015)
  • Comparison for TFPI level between Haemophilia A and Haemophilia B [ Time Frame: day 1 ]
    Comparison for TFPI level between Haemophilia A and Haemophilia B
  • 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
  • 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
Original Primary Outcome Measures Same as current
Change History Complete list of historical versions of study NCT02540187 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: September 1, 2015)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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)
  • 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)
  • 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)
  • 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)
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Tissue Factor Pathway Inhibitor (TFPI) and Haemorrhagic Manifestations in Haemophilia A and B Patients
Official Title Tissue Factor Pathway Inhibitor (TFPI) and Haemorrhagic Manifestations in Haemophilia A and B Patients
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.

Detailed Description Not Provided
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
blood specimen
Sampling Method Probability Sample
Study Population Haemophilia A and B patients between 18 and 65 years old, whatever the severity of their disease
Condition Hemophilia
Intervention Other: blood specimen
Study Groups/Cohorts
  • 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
    Intervention: 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
    Intervention: Other: blood specimen
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: September 1, 2015)
164
Original Estimated Enrollment Same as current
Actual Study Completion Date February 2016
Actual Primary Completion Date February 2016   (Final data collection date for primary outcome measure)
Eligibility 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).
Sex/Gender
Sexes Eligible for Study: Male
Ages 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries France
Removed Location Countries  
 
Administrative Information
NCT Number NCT02540187
Other Study ID Numbers 1108164
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Centre Hospitalier Universitaire de Saint Etienne
Study Sponsor Centre Hospitalier Universitaire de Saint Etienne
Collaborators Pfizer
Investigators Not Provided
PRS Account Centre Hospitalier Universitaire de Saint Etienne
Verification Date March 2016