Inter Individual Variability in Initiation Pathway Activation and Regulation and Phenotypic Heterogeneity in Patients With Haemophilia A and B

NCT ID: NCT03287999

Last Updated: 2019-03-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

250 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-09-19

Study Completion Date

2020-10-02

Brief Summary

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Severe haemophilia A and B (SHA, SHB) are X - linked inherited bleeding disorders, characterised by factor VIII and IX levels of \<1 IU/dL respectively. The mainstay of treatment in SHA and SHB is replacement therapy with intravenous infusions of factor VIII and IX. However, there is significant variability in the bleeding phenotype within severe haemophiliacs with some presenting with minimal bleeding episodes even on less intensive treatment regimens. A significant contributor to inter-individual variability in the bleeding phenotype is the coagulation phenotype, but there are no established assays in routine clinical practice that can be used to quantify this. This study aims to study novel assays and characterise the observed phenotypic heterogeneity.

Detailed Description

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Conditions

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Haemophilia

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Haemophilia patients

Persons with haemophilia A or B - 240 to be recruited

Thrombophilia screen

Intervention Type DIAGNOSTIC_TEST

Thrombophilia screen (including antithrombin activity (AT:Ac), protein S antigen (PS:free), protein C activity (PC:Ac) , genetic analysis for FV Leiden and Prothrombin 3'UTR mutations and screening for lupus anticoagulant.

Initiation pathway analysis

Intervention Type DIAGNOSTIC_TEST

Evaluation of inter-individual variability in regulation of TF.VIIa.Xa.TFPI complex (tissue factor, activated Factor VII, activated factor X, tissue factor pathway inhibitor)

Healthy volunteers

Healthy volunteers - 10 to be recruited

Thrombophilia screen

Intervention Type DIAGNOSTIC_TEST

Thrombophilia screen (including antithrombin activity (AT:Ac), protein S antigen (PS:free), protein C activity (PC:Ac) , genetic analysis for FV Leiden and Prothrombin 3'UTR mutations and screening for lupus anticoagulant.

Initiation pathway analysis

Intervention Type DIAGNOSTIC_TEST

Evaluation of inter-individual variability in regulation of TF.VIIa.Xa.TFPI complex (tissue factor, activated Factor VII, activated factor X, tissue factor pathway inhibitor)

Interventions

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Thrombophilia screen

Thrombophilia screen (including antithrombin activity (AT:Ac), protein S antigen (PS:free), protein C activity (PC:Ac) , genetic analysis for FV Leiden and Prothrombin 3'UTR mutations and screening for lupus anticoagulant.

Intervention Type DIAGNOSTIC_TEST

Initiation pathway analysis

Evaluation of inter-individual variability in regulation of TF.VIIa.Xa.TFPI complex (tissue factor, activated Factor VII, activated factor X, tissue factor pathway inhibitor)

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

1. Patients with haemophilia A or B (baseline FVIII/FIX level \<30%)
2. Age ≥ 18 years
3. Written informed consent in accordance with local and institutional guidelines.


1. Currently not receiving any antiplatelet or anticoagulant therapy or other drugs that can affect the coagulation system.
2. Age ≥ 18 years
3. Written informed consent in accordance with local and institutional guidelines.

Exclusion Criteria

1\. Patients currently enrolled into a clinical trial of investigational medicinal product for haemophilia.

Healthy Volunteers
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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Royal Free Hospital NHS Foundation Trust

OTHER

Sponsor Role lead

Responsible Party

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Pratima Chowdary

Dr Pratima Chowdary

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Pratima Chowdary

Role: PRINCIPAL_INVESTIGATOR

Royal Free Hospitals NHS Foundation Trust

Locations

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Royal Free Hospital

London, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Thomas Roberts

Role: CONTACT

02078302068

Facility Contacts

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Thomas Roberts

Role: primary

Other Identifiers

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11296

Identifier Type: -

Identifier Source: org_study_id

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