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

• Conditions: Haemophilia
• Interventions: Diagnostic Test: Thrombophilia screen; Diagnostic Test: Initiation pathway analysis

• Registration Number: NCT03287999
• Lead Sponsor: Royal Free Hospital NHS Foundation Trust

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-09-13
• Study First Submitted QC: 2017-09-15
• Study Start: 2017-09-19
• Study First Posted: 2017-09-19
• Status Verified: 2019-03
• Last Update Submitted: 2019-03-25
• Last Update Posted: 2019-03-27
• Primary Completion: 2019-10-02
• Study Completion: 2020-10-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Male
• Target Recruitment: 250

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Healthy volunteers	Initiation pathway analysis	Healthy volunteers - 10 to be recruited
Haemophilia patients	Thrombophilia screen	Persons with haemophilia A or B - 240 to be recruited
Haemophilia patients	Initiation pathway analysis	Persons with haemophilia A or B - 240 to be recruited
Healthy volunteers	Thrombophilia screen	Healthy volunteers - 10 to be recruited

Primary Outcome Measures

Name	Time	Method
Initiation pathway correlation with clinical phenotype	Within 18 months of consent	Correlate lab assays that characterise initiation pathway with clinical phenotype.

Secondary Outcome Measures

Name	Time	Method
Evaluation the sensitivity and specificity of global assays for disease severity and clinical phenotype.	Within 18 months of consent
Correlation analysis between activation threshold of initiation pathway to thrombin generation and clinical phenotype	Within 18 months of consent
Correlation analysis between FVIII:C/FIX:C levels and whole blood clotting time, thrombin generation in platelet poor plasma.	Within 18 months of consent

Trial Locations

Locations (1)

Royal Free Hospital; 🇬🇧 London, United Kingdom