<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/NCT03015025</url>
  </required_header>
  <id_info>
    <org_study_id>FC/HULP_005/2011</org_study_id>
    <nct_id>NCT03015025</nct_id>
  </id_info>
  <brief_title>Pharmacogenetic Dosage Algorithm for Acenocoumarol</brief_title>
  <official_title>Creation and Validation of a Pharmacogenetic Dosage Algorithm for Acenocoumarol in Patients With Venous Thromboembolic Disease, Atrial Fibrillation and/or Mechanical Valvular Heart Prosthesis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Instituto de Investigación Hospital Universitario La Paz</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Instituto de Investigación Hospital Universitario La Paz</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The use of coumarins has been a challenge for doctors because of its narrow therapeutic range&#xD;
      and they show great inter and intra-individual variability in the dose necessary to achieve&#xD;
      an international normalized ratio (INR) within the therapeutic range. Among the factors&#xD;
      influencing the interindividual variability in the dose required include age, weight, Vitamin&#xD;
      K in the diet, comorbidity as well as drug interactions and in recent years has also seen the&#xD;
      importance of pharmacogenetic factors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Demographic and clinical factors contribute approximately 20% to the total variability of&#xD;
      dose requirements. In recent years it has highlighted the close relationship between the dose&#xD;
      requirements of coumarin drugs and certain polymorphisms of genes involved in&#xD;
      pharmacokinetics and pharmacodynamics of these drugs. The use of dosing algorithms that&#xD;
      include pharmacogenetic information may help in the dose selection, improving efficacy and&#xD;
      reducing adverse events. Studies have shown the relationship between genotype variants of&#xD;
      CYP2C9 and VKORC1, CYP4F2 and apolipoprotein E (ApoE), which together with the demographic&#xD;
      and clinical variants can explain between 50-60% of the variability in the response to these&#xD;
      drugs.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2011</start_date>
  <completion_date type="Actual">October 2013</completion_date>
  <primary_completion_date type="Actual">October 2013</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>Creation of a pharmacogenetic algorithm of dosage for acenocoumarol</measure>
    <time_frame>Up to 5 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Validation of the pharmacogenetic algorithm.</measure>
    <time_frame>Up to 5 years</time_frame>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">340</enrollment>
  <condition>Atrial Fibrillation</condition>
  <condition>Venous Thromboses</condition>
  <condition>Cardiac Valve Disease</condition>
  <arm_group>
    <arm_group_label>Stable treatment with acenocoumarol</arm_group_label>
    <description>Patients in stable anticoagulant treatment with acenocoumarol for auricular fibrillation, venous thromboembolic disease and/or cardiac valve replacement.</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>Acenocoumarol</intervention_name>
    <description>A blood sample was collected for CYP2C9, VKORC1, CYP4F2, APOE and 2 variants of POR genotypes.</description>
    <arm_group_label>Stable treatment with acenocoumarol</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Patients' consent was requested for the preservation of their DNA sample, in case of new&#xD;
      genes related to the pharmacokinetics or pharmacodynamics of acenocoumarol are discovered in&#xD;
      the future.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients receiving stable anticoagulant treatment with acenocoumarol for auricular&#xD;
        fibrillation, venous thromboembolic disease and/or cardiac valve replacement in Hospital La&#xD;
        Paz and Barrio del Pilar primary care center.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with Auricular fibrillation, venous thromboembolic disease and cardiac valve&#xD;
             replacement receiving acenocoumarol.&#xD;
&#xD;
          -  Patients with stable dose of acenocoumarol (weekly dose variation of &lt;20% in the last&#xD;
             3 months).&#xD;
&#xD;
          -  Patients with an international normalised ratio within the range of 2 to 3 (in&#xD;
             Auricular Fibrillation and venous thromboembolic disease) or 2.5 to 3.5 (in cardiac&#xD;
             valve replacement) for at least the 3 previous consecutive months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with renal failure (calculated creatinine clearance ≤30 ml/min), hepatic&#xD;
             disease (stage C of Child Plough Stage), thyroid dysfunction and/or cancer.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Antonio Carcas, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Universitario La Paz</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Universitario La Paz</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>September 2011</verification_date>
  <study_first_submitted>January 2, 2017</study_first_submitted>
  <study_first_submitted_qc>January 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 9, 2017</study_first_posted>
  <last_update_submitted>January 5, 2017</last_update_submitted>
  <last_update_submitted_qc>January 5, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 9, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Acenocoumarol</keyword>
  <keyword>Cytochrome P450</keyword>
  <keyword>Pharmacogenetics</keyword>
  <keyword>Algorithm</keyword>
  <keyword>CYP2C9</keyword>
  <keyword>VKORC1</keyword>
  <keyword>CYP4F2</keyword>
  <keyword>P450 oxidoreductase (POR)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</mesh_term>
    <mesh_term>Thrombosis</mesh_term>
    <mesh_term>Venous Thrombosis</mesh_term>
    <mesh_term>Heart Valve Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acenocoumarol</mesh_term>
  </intervention_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/NCT03015025
org study id: FC/HULP_005/2011
nct id: NCT03015025
lead sponsor: 
has dmc: No
The use of coumarins has been a challenge for doctors because of its narrow therapeutic range
      and they show great inter and intra-individual variability in the dose necessary to achieve
      an international normalized ratio (INR) within the therapeutic range. Among the factors
      influencing the interindividual variability in the dose required include age, weight, Vitamin
      K in the diet, comorbidity as well as drug interactions and in recent years has also seen the
      importance of pharmacogenetic factors.
Demographic and clinical factors contribute approximately 20% to the total variability of
      dose requirements. In recent years it has highlighted the close relationship between the dose
      requirements of coumarin drugs and certain polymorphisms of genes involved in
      pharmacokinetics and pharmacodynamics of these drugs. The use of dosing algorithms that
      include pharmacogenetic information may help in the dose selection, improving efficacy and
      reducing adverse events. Studies have shown the relationship between genotype variants of
      CYP2C9 and VKORC1, CYP4F2 and apolipoprotein E (ApoE), which together with the demographic
      and clinical variants can explain between 50-60% of the variability in the response to these
      drugs.
observational model: Cohort
time perspective: Prospective
measure: Creation of a pharmacogenetic algorithm of dosage for acenocoumarol
time frame: Up to 5 years
measure: Validation of the pharmacogenetic algorithm.
time frame: Up to 5 years
arm group label: Stable treatment with acenocoumarol
description: Patients in stable anticoagulant treatment with acenocoumarol for auricular fibrillation, venous thromboembolic disease and/or cardiac valve replacement.
intervention type: Genetic
intervention name: Acenocoumarol
description: A blood sample was collected for CYP2C9, VKORC1, CYP4F2, APOE and 2 variants of POR genotypes.
arm group label: Stable treatment with acenocoumarol
Patients' consent was requested for the preservation of their DNA sample, in case of new
      genes related to the pharmacokinetics or pharmacodynamics of acenocoumarol are discovered in
      the future.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Antonio Carcas, MD, PhD
role: Principal Investigator
affiliation: Hospital Universitario La Paz
facility: 
country: Spain
responsible party type: Sponsor
mesh term: Atrial Fibrillation
mesh term: Thrombosis
mesh term: Venous Thrombosis
mesh term: Heart Valve Diseases
mesh term: Acenocoumarol
sharing ipd: No