<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/NCT03835780</url>
  </required_header>
  <id_info>
    <org_study_id>P004</org_study_id>
    <nct_id>NCT03835780</nct_id>
  </id_info>
  <brief_title>The Risk of Venous Thromboembolism in Systemic Inflammatory Disorders: a United Kingdom (UK) Matched Cohort Study</brief_title>
  <official_title>The Risk of Venous Thromboembolism in Systemic Inflammatory Disorders: a UK Matched Cohort Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Momentum Data</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Surrey</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Momentum Data</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Blood clots occurring in the legs and in the lungs are relatively common; they occur in&#xD;
      around 3 in a 1000 people per year. They can cause disability and are also potentially life&#xD;
      threatening. When a clot occurs in the legs it is called a deep vein thrombosis or DVT. When&#xD;
      they occur in the lungs they are called a pulmonary embolism or PE. The risk for DVT and PE&#xD;
      is higher in people with conditions which cause inflammation. The most common of these are&#xD;
      inflammatory bowel disease (ulcerative colitis and Crohn's disease), rheumatoid arthritis,&#xD;
      and psoriatic arthritis (a condition comprised of psoriasis and joint inflammation).&#xD;
&#xD;
      What is not known is how much higher the risk of DVT and PE is in these groups compared with&#xD;
      people without inflammatory disease, and what causes the excess risk in these people. This&#xD;
      study aims to assess the measure the exact increase in risk for DVT and PE in people with&#xD;
      these inflammatory conditions and to identify which risk factors are most strongly associated&#xD;
      with the increased risk. These data should help with an understand the causes of blood clot&#xD;
      risk in these inflammatory conditions and in identify targets for reducing risk.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background&#xD;
&#xD;
      Venous thromboembolism (VTE), comprising pulmonary embolism (PE) and deep vein thrombosis&#xD;
      (DVT), are common and associated with significant morbidity and mortality. VTE risk is higher&#xD;
      in chronic inflammatory conditions including inflammatory bowel disease (IBD) and rheumatoid&#xD;
      arthritis (RA) compared to the general population. Evidence for differential VTE risk in&#xD;
      other inflammatory diseases, notably psoriatic arthritis (PsA) and vasculitis, is more&#xD;
      limited. Risk factors for VTE have been described in the general population, but there has&#xD;
      been little interrogation of VTE risk factors for individuals with chronic inflammatory&#xD;
      conditions and their association with subsequent VTE.&#xD;
&#xD;
      Objective&#xD;
&#xD;
      This study aims to describe the prevalence of VTE risk and risk factors in individuals with&#xD;
      systemic inflammatory disorders in a contemporary real-world population, by disease type&#xD;
      (IBD, RA, and PsA) and relative to a control population without systemic inflammatory&#xD;
      disease. In the same cohorts a further comparison will be performed of the influence of VTE&#xD;
      risk factors on risk of VTE events in individuals with systemic inflammatory disorders.&#xD;
&#xD;
      Method&#xD;
&#xD;
      A retrospective cohort study will be performed to compare VTE risk and VTE risk factors in&#xD;
      adults with IBD, RA, and PsA and matched controls between January 1, 1998 and January 1,&#xD;
      2018, within the Royal College of General Practitioners (RCGP) Research and Surveillance&#xD;
      Centre (RSC) network. In the cohorts with and without inflammatory conditions estimate will&#xD;
      be determined for the risk of VTE overall, and for PE and DVT separately, using unadjusted&#xD;
      Cox proportional hazards models, stratified by matched set (exposed cohort versus unexposed&#xD;
      cohort), to provide overall hazard ratios for the association with each outcome. Models will&#xD;
      be subsequently adjusted for sociodemographic and clinical and VTE risk factors in&#xD;
      multivariable analysis to explore potentially important associations with VTE. The same&#xD;
      analyses for each autoimmune condition will be repeated separately. Prespecified sensitivity&#xD;
      analyses will be performed to explore the robustness of any potential associations.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 1, 2019</start_date>
  <completion_date type="Actual">December 1, 2019</completion_date>
  <primary_completion_date type="Actual">August 1, 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>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Time to venous thromboembolism (VTE)</measure>
    <time_frame>A 20 year analysis period (1999-2018 inclusive)</time_frame>
    <description>Time to VTE (a composite of PE and DVT) in individuals with systemic inflammatory disorders compared to population controls.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to pulmonary embolism (PE)</measure>
    <time_frame>A 20 year analysis period (1999-2018 inclusive)</time_frame>
    <description>Time to PE in individuals with systemic inflammatory disorders compared to population controls.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to deep vein thrombosis (DVT)</measure>
    <time_frame>A 20 year analysis period (1999-2018 inclusive)</time_frame>
    <description>Time to DVT in individuals with systemic inflammatory disorders compared to population controls.</description>
  </secondary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Actual">266890</enrollment>
  <condition>Venous Thromboses</condition>
  <condition>Venous Thromboembolism</condition>
  <condition>Deep Vein Thrombosis</condition>
  <condition>Pulmonary Embolism</condition>
  <condition>Rheumatoid Arthritis</condition>
  <condition>Inflammatory Bowel Diseases</condition>
  <condition>Ulcerative Colitis</condition>
  <condition>Crohn Disease</condition>
  <condition>Psoriatic Arthritis</condition>
  <arm_group>
    <arm_group_label>People with inflammatory bowel disease</arm_group_label>
    <description>All individuals with an existing or incident diagnosis of IBD during the study period</description>
  </arm_group>
  <arm_group>
    <arm_group_label>People with rheumatoid arthritis</arm_group_label>
    <description>All individuals with an existing or incident diagnosis of RA during the study period</description>
  </arm_group>
  <arm_group>
    <arm_group_label>People with psoriatic arthritis</arm_group_label>
    <description>All individuals with an existing or incident diagnosis of IBD during the study period</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Controls</arm_group_label>
    <description>Age, gender and primary care practice matched individuals without an existing or incident diagnosis of IBD, RA, or PsA during the study period</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>No intervention</intervention_name>
    <description>A observation of outcomes in usual practice</description>
    <arm_group_label>Controls</arm_group_label>
    <arm_group_label>People with inflammatory bowel disease</arm_group_label>
    <arm_group_label>People with psoriatic arthritis</arm_group_label>
    <arm_group_label>People with rheumatoid arthritis</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        The exposed cohort will include all individuals with an existing or incident diagnosis of&#xD;
        IBD, RA or PsA (systemic inflammatory diseases) in the RCGP RSC over the study period. IBD,&#xD;
        RA or PsA will be identified using Read diagnostic codes previously validated in UK primary&#xD;
        care studies.&#xD;
&#xD;
        The matched unexposed cohort will be defined by matching individuals in the exposed cohort&#xD;
        with individuals who have never been diagnosed with a systemic inflammatory disease either&#xD;
        prior to or during the study period by age and sex at GP practice level. Unexposed&#xD;
        individuals will require at least one year of follow-up when matched to minimize the risk&#xD;
        they had a non-recorded existing diagnosis of a systemic inflammatory disease of interest.&#xD;
        Follow-up for each matched individual will begin at the start of follow-up of their matched&#xD;
        counterpart.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients (aged ≥18) contributing to RCGP RCS primary care database between&#xD;
             January 1, 1998 and January 1, 2018, will be eligible for inclusion&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  People with IBD which cannot be classified or is not ulcerative colitis or Crohn's&#xD;
             disease will be excluded.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Momentum Data Ltd</name>
      <address>
        <city>London</city>
        <zip>WC1X 8QT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>January 17, 2019</study_first_submitted>
  <study_first_submitted_qc>February 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 11, 2019</study_first_posted>
  <last_update_submitted>January 14, 2020</last_update_submitted>
  <last_update_submitted_qc>January 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthritis</mesh_term>
    <mesh_term>Arthritis, Psoriatic</mesh_term>
    <mesh_term>Crohn Disease</mesh_term>
    <mesh_term>Inflammatory Bowel Diseases</mesh_term>
    <mesh_term>Pulmonary Embolism</mesh_term>
    <mesh_term>Thrombosis</mesh_term>
    <mesh_term>Embolism</mesh_term>
    <mesh_term>Thromboembolism</mesh_term>
    <mesh_term>Venous Thromboembolism</mesh_term>
    <mesh_term>Venous Thrombosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Individual patient data is confidential but can be made available in an anonymised form to bone fide researchers subject to the required data protection training and other requirements. All data will remain behind a firewall and will only be available for access through a secured computer network.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 6, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/80/NCT03835780/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03835780
org study id: P004
nct id: NCT03835780
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
Blood clots occurring in the legs and in the lungs are relatively common; they occur in
      around 3 in a 1000 people per year. They can cause disability and are also potentially life
      threatening. When a clot occurs in the legs it is called a deep vein thrombosis or DVT. When
      they occur in the lungs they are called a pulmonary embolism or PE. The risk for DVT and PE
      is higher in people with conditions which cause inflammation. The most common of these are
      inflammatory bowel disease (ulcerative colitis and Crohn's disease), rheumatoid arthritis,
      and psoriatic arthritis (a condition comprised of psoriasis and joint inflammation).

      What is not known is how much higher the risk of DVT and PE is in these groups compared with
      people without inflammatory disease, and what causes the excess risk in these people. This
      study aims to assess the measure the exact increase in risk for DVT and PE in people with
      these inflammatory conditions and to identify which risk factors are most strongly associated
      with the increased risk. These data should help with an understand the causes of blood clot
      risk in these inflammatory conditions and in identify targets for reducing risk.
Background

      Venous thromboembolism (VTE), comprising pulmonary embolism (PE) and deep vein thrombosis
      (DVT), are common and associated with significant morbidity and mortality. VTE risk is higher
      in chronic inflammatory conditions including inflammatory bowel disease (IBD) and rheumatoid
      arthritis (RA) compared to the general population. Evidence for differential VTE risk in
      other inflammatory diseases, notably psoriatic arthritis (PsA) and vasculitis, is more
      limited. Risk factors for VTE have been described in the general population, but there has
      been little interrogation of VTE risk factors for individuals with chronic inflammatory
      conditions and their association with subsequent VTE.

      Objective

      This study aims to describe the prevalence of VTE risk and risk factors in individuals with
      systemic inflammatory disorders in a contemporary real-world population, by disease type
      (IBD, RA, and PsA) and relative to a control population without systemic inflammatory
      disease. In the same cohorts a further comparison will be performed of the influence of VTE
      risk factors on risk of VTE events in individuals with systemic inflammatory disorders.

      Method

      A retrospective cohort study will be performed to compare VTE risk and VTE risk factors in
      adults with IBD, RA, and PsA and matched controls between January 1, 1998 and January 1,
      2018, within the Royal College of General Practitioners (RCGP) Research and Surveillance
      Centre (RSC) network. In the cohorts with and without inflammatory conditions estimate will
      be determined for the risk of VTE overall, and for PE and DVT separately, using unadjusted
      Cox proportional hazards models, stratified by matched set (exposed cohort versus unexposed
      cohort), to provide overall hazard ratios for the association with each outcome. Models will
      be subsequently adjusted for sociodemographic and clinical and VTE risk factors in
      multivariable analysis to explore potentially important associations with VTE. The same
      analyses for each autoimmune condition will be repeated separately. Prespecified sensitivity
      analyses will be performed to explore the robustness of any potential associations.
observational model: Cohort
time perspective: Retrospective
measure: Time to venous thromboembolism (VTE)
time frame: A 20 year analysis period (1999-2018 inclusive)
description: Time to VTE (a composite of PE and DVT) in individuals with systemic inflammatory disorders compared to population controls.
measure: Time to pulmonary embolism (PE)
time frame: A 20 year analysis period (1999-2018 inclusive)
description: Time to PE in individuals with systemic inflammatory disorders compared to population controls.
measure: Time to deep vein thrombosis (DVT)
time frame: A 20 year analysis period (1999-2018 inclusive)
description: Time to DVT in individuals with systemic inflammatory disorders compared to population controls.
arm group label: People with inflammatory bowel disease
description: All individuals with an existing or incident diagnosis of IBD during the study period
arm group label: People with rheumatoid arthritis
description: All individuals with an existing or incident diagnosis of RA during the study period
arm group label: People with psoriatic arthritis
description: All individuals with an existing or incident diagnosis of IBD during the study period
arm group label: Controls
description: Age, gender and primary care practice matched individuals without an existing or incident diagnosis of IBD, RA, or PsA during the study period
intervention type: Other
intervention name: No intervention
description: A observation of outcomes in usual practice
arm group label: Controls
arm group label: People with inflammatory bowel disease
arm group label: People with psoriatic arthritis
arm group label: People with rheumatoid arthritis
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Arthritis, Psoriatic
mesh term: Crohn Disease
mesh term: Inflammatory Bowel Diseases
mesh term: Pulmonary Embolism
mesh term: Thrombosis
mesh term: Embolism
mesh term: Thromboembolism
mesh term: Venous Thromboembolism
mesh term: Venous Thrombosis
sharing ipd: Yes
ipd description: Individual patient data is confidential but can be made available in an anonymised form to bone fide researchers subject to the required data protection training and other requirements. All data will remain behind a firewall and will only be available for access through a secured computer network.
ipd info type: Study Protocol
provided document: 