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

Haemophilia Clinical Trial

— InPath  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03287999
• Other study ID #: 11296
• Status: Recruiting
• Start date: September 19, 2017
• Est. completion date: October 2, 2020

Study information

• Verified date: March 2019
• Source: Royal Free Hospital NHS Foundation Trust
• Contact: Thomas Roberts
• Phone: 02078302068
• Email: thomas.roberts1[@]nhs.net
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: October 2, 2020
• Est. primary completion date: October 2, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years and older

Eligibility

Patients

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.

Exclusion Criteria:

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

Healthy Volunteers

Inclusion Criteria:

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.

Related Conditions & MeSH terms

• Haemophilia
• Hemophilia A

Intervention

Diagnostic Test:
• 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.
• 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)

Locations

Country	Name	City	State
United Kingdom	Royal Free Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
Royal Free Hospital NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Initiation pathway correlation with clinical phenotype	Correlate lab assays that characterise initiation pathway with clinical phenotype.	Within 18 months of consent
Secondary	Correlation analysis between FVIII:C/FIX:C levels and whole blood clotting time, thrombin generation in platelet poor plasma.		Within 18 months of consent
Secondary	Evaluation the sensitivity and specificity of global assays for disease severity and clinical phenotype.		Within 18 months of consent
Secondary	Correlation analysis between activation threshold of initiation pathway to thrombin generation and clinical phenotype		Within 18 months of consent