HemophiliaNCT02540187
Tissue Factor Pathway Inhibitor (TFPI) and Haemorrhagic Manifestations in Haemophilia A and B Patients
An observational study of Hemophilia, run by Centre Hospitalier Universitaire de Saint Etienne at 7 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years, men only
- Conditions the study is for
- Hemophilia
- What is being tested?
- blood specimen
- How many people
- 164 participants
- Where
- 7 sitesFrance
- Study dates
- Feb 2012to Feb 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Men only
- No healthy volunteers
- Adult, Older adult
Study population: Haemophilia A and B patients between 18 and 65 years old, whatever the severity of their disease
Who may be able to join
- 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.
Who cannot join
- - 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).
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
France7 sites
CHRU Lille
Lille
HCL
Lyon
AP-HM
Marseille
Chu Nancy
Nancy
Chu Reims
Reims
CHU Saint-Etienne
Saint-Etienne, 42055
Chu Tours
Tours
About this study
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.
- Conditions
- Hemophilia
- Being tested
- blood specimen
- Keywords
- haemophilia, TFPI, thrombin generation, hemorrhagic score
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood specimenOther
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Other: blood specimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison for TFPI level between Haemophilia A and Haemophilia B
Comparison for TFPI level between Haemophilia A and Haemophilia B
Measured: day 1
Comparison for TFPI level between severe Haemophilia A and severe Haemophilia B
Comparison for TFPI level between severe Haemophilia A and severe Haemophilia B
Measured: Day 1
Comparison for TFPI level between moderate or mild Haemophilia A and moderate or mild Haemophilia B
Comparison for TFPI level between moderate or mild Haemophilia A and moderate or mild Haemophilia B
Measured: Day 1
Secondary outcomes (14)
Correlation between free TFPI and hemorrhagic score
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
Measured: day 1
Correlation between TFPI activity and hemorrhagic score
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
Measured: day 1
Correlation between Endogenous Thrombin Potential (ETP) and free TFPI
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
Measured: day 1
Correlation between Lag Time and free TFPI
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
Measured: day 1
Correlation between Peak value and free TFPI
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
Measured: day 1
Correlation between Time to Peak and free TFPI
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
Measured: day 1
Correlation between ETP and hemorrhagic score
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.
Measured: day 1
Correlation between Lag Time and hemorrhagic score
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.
Measured: day 1
Correlation between Peak Value and hemorrhagic score
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.
Measured: day 1
Correlation between Time to Peak and hemorrhagic score
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.
Measured: day 1
Comparison for ETP between haemophilia A et Haemophilia B
Endogenous Thrombin Potential (i.e. the aera under the thrombin generation curve, nM.min) is measured by Thromboplastin Generation Test (TGTs)
Measured: Day 1
Comparison for lag time between haemophilia A et Haemophilia B
Lag time (min) of the thrombin generation curve is measured by thromboplastin Generation Test (TGTs)
Measured: Day 1
Comparison for Peak Value between haemophilia A et Haemophilia B
Peak Value (PV, nmol thrombin) of the thrombin generation curve is measured by thromboplastin Generation Test (TGTs)
Measured: Day 1
Comparison for Time to Peak between haemophilia A et Haemophilia B
Time to Peak (TTP, min) of the thrombin generation curve is measured by thromboplastin Generation Test (TGTs)
Measured: day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2015 (estimated)
- Study startFeb 2012
- Primary completionFeb 2016
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HemophiliaStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de Saint EtienneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 164 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02540187
- Sponsor's protocol ID
- 1108164
- Status last verified
- Mar 2016
- First submitted
- 1 Sep 2015
- Last updated
- 10 Mar 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tissue Factor Pathway Inhibitor (TFPI) and Haemorrhagic Manifestations in Haemophilia A and B Patients
- ClinicalTrials.gov ID
- NCT02540187
- Acronym / sponsor ID
- 1108164
- Conditions
- Hemophilia
- Keywords
- haemophilia, TFPI, thrombin generation, hemorrhagic score
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 164 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de Saint EtienneUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- Feb 2012
- Primary completion
- Feb 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 3 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| haemophilia A | – | Other: blood specimen1. 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 |
| Haemophilia B | – | Other: blood specimen1. 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 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Haemophilia A and B patients between 18 and 65 years old, whatever the severity of their disease
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (6 listed)
- - 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| blood specimen | Other | Haemophilia B, haemophilia A |
Primary outcome
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
14 secondary outcomes
Correlation between free TFPI and hemorrhagic score
Time frame: day 1
Correlation between TFPI activity and hemorrhagic score
Time frame: day 1
Correlation between Endogenous Thrombin Potential (ETP) and free TFPI
Time frame: day 1
Correlation between Lag Time and free TFPI
Time frame: day 1
Correlation between Peak value and free TFPI
Time frame: day 1
Correlation between Time to Peak and free TFPI
Time frame: day 1
Correlation between ETP and hemorrhagic score
Time frame: day 1
Correlation between Lag Time and hemorrhagic score
Time frame: day 1
Correlation between Peak Value and hemorrhagic score
Time frame: day 1
Correlation between Time to Peak and hemorrhagic score
Time frame: day 1
Comparison for ETP between haemophilia A et Haemophilia B
Time frame: Day 1
Comparison for lag time between haemophilia A et Haemophilia B
Time frame: Day 1
Comparison for Peak Value between haemophilia A et Haemophilia B
Time frame: Day 1
Comparison for Time to Peak between haemophilia A et Haemophilia B
Time frame: day 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hemophilia, run by Centre Hospitalier Universitaire de Saint Etienne at 7 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison for TFPI level between Haemophilia A and Haemophilia B (time frame: day 1). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2016.