Clinical trial NCT03287999: Inter Individual Variability in Initiation Pathway Activation and Regulation and Phenotypic Heterogeneity in Patients With Haemophilia A and B
Official title: Inter Individual Variability in Initiation Pathway Activation and Regulation and Phenotypic Heterogeneity in Patients With Haemophilia A and B
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Haemophilia
Lead sponsor: Royal Free Hospital NHS Foundation Trust
Sponsor class: OTHER
First posted: 2017-09-19
Enrollment: 250
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will include patients severe or moderate haemophilia A or B who are currently attending study sites for routine follow up visits. In addition, 10 healthy volunteers will also be recruited to act as controls

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Initiation pathway correlation with clinical phenotype
timeFrame: Within 18 months of consent
Secondary outcomes:
measure: Correlation analysis between FVIII:C/FIX:C levels and whole blood clotting time, thrombin generation in platelet poor plasma.
timeFrame: Within 18 months of consent
measure: Evaluation the sensitivity and specificity of global assays for disease severity and clinical phenotype.
timeFrame: Within 18 months of consent
measure: Correlation analysis between activation threshold of initiation pathway to thrombin generation and clinical phenotype
timeFrame: Within 18 months of consent
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Royal Free Hospital
Study officials:
affiliation: Royal Free Hospitals NHS Foundation Trust
name: Pratima Chowdary
role: PRINCIPAL_INVESTIGATOR
References: