<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03287999</url>
  </required_header>
  <id_info>
    <org_study_id>11296</org_study_id>
    <nct_id>NCT03287999</nct_id>
  </id_info>
  <brief_title>Inter Individual Variability in Initiation Pathway Activation and Regulation and Phenotypic Heterogeneity in Patients With Haemophilia A and B</brief_title>
  <acronym>InPath</acronym>
  <official_title>Inter Individual Variability in Initiation Pathway Activation and Regulation and Phenotypic Heterogeneity in Patients With Haemophilia A and B</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Royal Free Hospital NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Royal Free Hospital NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Severe haemophilia A and B (SHA, SHB) are X - linked inherited bleeding disorders,&#xD;
      characterised by factor VIII and IX levels of &lt;1 IU/dL respectively. The mainstay of&#xD;
      treatment in SHA and SHB is replacement therapy with intravenous infusions of factor VIII and&#xD;
      IX. However, there is significant variability in the bleeding phenotype within severe&#xD;
      haemophiliacs with some presenting with minimal bleeding episodes even on less intensive&#xD;
      treatment regimens. A significant contributor to inter-individual variability in the bleeding&#xD;
      phenotype is the coagulation phenotype, but there are no established assays in routine&#xD;
      clinical practice that can be used to quantify this. This study aims to study novel assays&#xD;
      and characterise the observed phenotypic heterogeneity.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">September 19, 2017</start_date>
  <completion_date type="Anticipated">October 2, 2020</completion_date>
  <primary_completion_date type="Anticipated">October 2, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Initiation pathway correlation with clinical phenotype</measure>
    <time_frame>Within 18 months of consent</time_frame>
    <description>Correlate lab assays that characterise initiation pathway with clinical phenotype.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Correlation analysis between FVIII:C/FIX:C levels and whole blood clotting time, thrombin generation in platelet poor plasma.</measure>
    <time_frame>Within 18 months of consent</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation the sensitivity and specificity of global assays for disease severity and clinical phenotype.</measure>
    <time_frame>Within 18 months of consent</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation analysis between activation threshold of initiation pathway to thrombin generation and clinical phenotype</measure>
    <time_frame>Within 18 months of consent</time_frame>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">250</enrollment>
  <condition>Haemophilia</condition>
  <arm_group>
    <arm_group_label>Haemophilia patients</arm_group_label>
    <description>Persons with haemophilia A or B - 240 to be recruited</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy volunteers</arm_group_label>
    <description>Healthy volunteers - 10 to be recruited</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Thrombophilia screen</intervention_name>
    <description>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.</description>
    <arm_group_label>Haemophilia patients</arm_group_label>
    <arm_group_label>Healthy volunteers</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Initiation pathway analysis</intervention_name>
    <description>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)</description>
    <arm_group_label>Haemophilia patients</arm_group_label>
    <arm_group_label>Healthy volunteers</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood plasma&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The study population will include patients severe or moderate haemophilia A or B who are&#xD;
        currently attending study sites for routine follow up visits. In addition, 10 healthy&#xD;
        volunteers will also be recruited to act as controls&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Patients&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with haemophilia A or B (baseline FVIII/FIX level &lt;30%)&#xD;
&#xD;
          2. Age ≥ 18 years&#xD;
&#xD;
          3. Written informed consent in accordance with local and institutional guidelines.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        1. Patients currently enrolled into a clinical trial of investigational medicinal product&#xD;
        for haemophilia.&#xD;
&#xD;
        Healthy Volunteers&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          1. Currently not receiving any antiplatelet or anticoagulant therapy or other drugs that&#xD;
             can affect the coagulation system.&#xD;
&#xD;
          2. Age ≥ 18 years&#xD;
&#xD;
          3. Written informed consent in accordance with local and institutional guidelines.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pratima Chowdary</last_name>
    <role>Principal Investigator</role>
    <affiliation>Royal Free Hospitals NHS Foundation Trust</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Thomas Roberts</last_name>
    <phone>02078302068</phone>
    <email>thomas.roberts1@nhs.net</email>
  </overall_contact>
  <location>
    <facility>
      <name>Royal Free Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Thomas Roberts</last_name>
    </contact>
    <investigator>
      <last_name>Pratima Chowdary</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>September 13, 2017</study_first_submitted>
  <study_first_submitted_qc>September 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 19, 2017</study_first_posted>
  <last_update_submitted>March 25, 2019</last_update_submitted>
  <last_update_submitted_qc>March 25, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 27, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Royal Free Hospital NHS Foundation Trust</investigator_affiliation>
    <investigator_full_name>Pratima Chowdary</investigator_full_name>
    <investigator_title>Dr Pratima Chowdary</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hemophilia A</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03287999
org study id: 11296
nct id: NCT03287999
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
observational model: Cohort
time perspective: Prospective
measure: Initiation pathway correlation with clinical phenotype
time frame: Within 18 months of consent
description: Correlate lab assays that characterise initiation pathway with clinical phenotype.
measure: Correlation analysis between FVIII:C/FIX:C levels and whole blood clotting time, thrombin generation in platelet poor plasma.
time frame: Within 18 months of consent
measure: Evaluation the sensitivity and specificity of global assays for disease severity and clinical phenotype.
time frame: Within 18 months of consent
measure: Correlation analysis between activation threshold of initiation pathway to thrombin generation and clinical phenotype
time frame: Within 18 months of consent
arm group label: Haemophilia patients
description: Persons with haemophilia A or B - 240 to be recruited
arm group label: Healthy volunteers
description: Healthy volunteers - 10 to be recruited
intervention type: Diagnostic Test
intervention name: Thrombophilia screen
description: 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.
arm group label: Haemophilia patients
arm group label: Healthy volunteers
intervention type: Diagnostic Test
intervention name: Initiation pathway analysis
description: 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)
arm group label: Haemophilia patients
arm group label: Healthy volunteers
Blood plasma
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Pratima Chowdary
role: Principal Investigator
affiliation: Royal Free Hospitals NHS Foundation Trust
last name: Thomas Roberts
phone: 02078302068
email: thomas.roberts1@nhs.net
facility: 
status: Recruiting
contact: 
investigator: 
country: United Kingdom
responsible party type: Principal Investigator
investigator affiliation: Royal Free Hospital NHS Foundation Trust
investigator full name: Pratima Chowdary
investigator title: Dr Pratima Chowdary
mesh term: Hemophilia A
sharing ipd: No