<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/NCT03243604</url>
  </required_header>
  <id_info>
    <org_study_id>CIC1421-17-08</org_study_id>
    <nct_id>NCT03243604</nct_id>
  </id_info>
  <brief_title>cARdiotoxicity Profile of aBIraTeRone in prostAte Cancer : a pharmacoviGilancE Study</brief_title>
  <acronym>ARBITRAGE</acronym>
  <official_title>Cardiotoxicity of Abiraterone in the National French Pharmacovigilance Database and in the European Clinical Trials Database (EudraCT)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Groupe Hospitalier Pitie-Salpetriere</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Groupe Hospitalier Pitie-Salpetriere</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>
      Abiraterone associated with prednisone is used in prostate cancer. Abiraterone is a selective&#xD;
      small-molecule inhibiting cytochrome P450 17A1 (CYP17A1), a key enzyme in androgen synthesis.&#xD;
&#xD;
      CYP17A inhibition is also responsible for mineral corticosteroid related adverse events as&#xD;
      hypokaliemia, fluid retention, and hypertension. Primary hyperaldosteronism is associated&#xD;
      with cardiovascular toxicities such as atrial fibrillation and cardiac failure. Other&#xD;
      androgen-deprivation therapies are not associated with increased mineral corticosteroid&#xD;
      level.&#xD;
&#xD;
      This study investigates reports of cardiovascular toxicities for treatment including L02 (sex&#xD;
      hormones used in treatment of neoplastic diseases), and G03 (sex hormones) used in prostate&#xD;
      cancer in the French pharmacovigilance database and in the EudraCT database.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Due to its peculiar pharmacology, abiraterone is potentially associated with more&#xD;
      cardiotoxicity as compared to other androgen-deprivation therapies. This study investigates&#xD;
      the main characteristics of patients affected by cardiovascular side effects of which&#xD;
      supraventricular arrhythmias (including atrial fibrillation, atrial flutter, supraventricular&#xD;
      tachycardia), and cardiac failure imputed to drugs classified as L02, and G03 according to&#xD;
      anatomical therapeutic chemical (ATC) classification. A causality assessment according to the&#xD;
      World Health Organization-The Uppsala Monitoring Centre (WHO-UMC) is systematically applied.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 16, 2017</start_date>
  <completion_date type="Actual">July 13, 2017</completion_date>
  <primary_completion_date type="Actual">July 13, 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Analysis of disproportionality of reports for cardiotoxicity associated with abiraterone as compared to enzalutamide by performing a case- non-case study</measure>
    <time_frame>2 months</time_frame>
    <description>Analysis of disproportionality of reports for cardiotoxicity associated with abiraterone as compared to enzalutamide by performing a case- non-case study</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Compare the reporting of suspected drug-induced supraventricular arrhythmias with abiraterone as compared to enzalutamide by performing a disproportionality analysis</measure>
    <time_frame>2 months</time_frame>
    <description>Compare the reporting of suspected drug-induced supraventricular arrhythmias with abiraterone as compared to enzalutamide by performing a disproportionality analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the reporting of drug-induced cardiac failure with abiraterone as compared to enzalutamide by performing a disproportionality analysis</measure>
    <time_frame>2 months</time_frame>
    <description>Compare the reporting of drug-induced cardiac failure with abiraterone as compared to enzalutamide by performing a disproportionality analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the reporting of drug-induced cardiac failure and/or supraventricular arrhythmias with abiraterone as compared to other androgen-deprivation therapies by performing a disproportionality analysis</measure>
    <time_frame>2 months</time_frame>
    <description>Compare the reporting of drug-induced cardiac failure and/or supraventricular arrhythmias with abiraterone as compared to other androgen-deprivation therapies by performing a disproportionality analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Description of other mineralocorticoid related adverse events (hypokaliemia, fluid retention, and hypertension) when the cardio toxicity occurs</measure>
    <time_frame>2 months</time_frame>
    <description>Description of other mineralocorticoid related adverse events (hypokaliemia, fluid retention, and hypertension) when the cardio toxicity occurs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Description of the population of patients having a cardio-vascular adverse event</measure>
    <time_frame>2 months</time_frame>
    <description>Description of the population of patients having a cardio-vascular adverse event</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Description of the duration of treatment when the toxicity happens (role of cumulative dose)</measure>
    <time_frame>2 months</time_frame>
    <description>Description of the duration of treatment when the toxicity happens (role of cumulative dose)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Description of the drug-drug interactions associated with adverse events</measure>
    <time_frame>2 months</time_frame>
    <description>Description of the drug-drug interactions associated with adverse events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Causality assessment of reported cardiovascular events according to the WHO-UMC system</measure>
    <time_frame>2 months</time_frame>
    <description>Causality assessment of reported cardiovascular events according to the WHO-UMC system</description>
  </secondary_outcome>
  <enrollment type="Actual">1717</enrollment>
  <condition>Arrhythmias, Cardiac</condition>
  <condition>Atrial Fibrillation and Flutter</condition>
  <condition>Tachycardia, Supraventricular</condition>
  <condition>Cardiac Failure</condition>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>L02 (sex hormones used in treatment of neoplastic diseases) and G03 (sex hormones)</intervention_name>
    <description>Androgen-deprivation therapies including L02 (sex hormones used in treatment of neoplastic diseases), and G03 (sex hormones)</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        The population is selected in the French pharmacovigilance database and EudraCT database&#xD;
        from 01/01/1985 to May 2017 and included patients treated with hormonal therapies included&#xD;
        in the ATC L02, and G03&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Case reported in the French pharmacovigilance database from 01/01/1985 to 16/05/2017&#xD;
&#xD;
          -  Case reported in the EudraCT database to May 2017&#xD;
&#xD;
          -  Adverse event reported were including the MedDRA terms: SOC Cardiac Disorders; SOC&#xD;
             Vascular Disorders; HLT Death, Sudden Death; HLGT Water, electrolyte and mineral&#xD;
             investigations; HLGT Cardiac and vascular investigations (excl enzyme tests); and PT&#xD;
             Syncope.&#xD;
&#xD;
          -  Patients treated with hormonal therapies included in the ATC L02, and G03&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Chronology not compatible between the drug and the toxicity&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Male</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Centre Régional de Pharmaco-vigilance - Paris, Pitié-Salpétrière</name>
      <address>
        <city>Paris</city>
        <state>Ile De France</state>
        <zip>75013</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>July 20, 2017</study_first_submitted>
  <study_first_submitted_qc>August 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 9, 2017</study_first_posted>
  <last_update_submitted>October 17, 2018</last_update_submitted>
  <last_update_submitted_qc>October 17, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 18, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Groupe Hospitalier Pitie-Salpetriere</investigator_affiliation>
    <investigator_full_name>Joe Elie Salem</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Cardiotoxicity</keyword>
  <keyword>abiraterone acetate</keyword>
  <keyword>androgen antagonist</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</mesh_term>
    <mesh_term>Arrhythmias, Cardiac</mesh_term>
    <mesh_term>Tachycardia</mesh_term>
    <mesh_term>Cardiotoxicity</mesh_term>
    <mesh_term>Heart Failure</mesh_term>
    <mesh_term>Tachycardia, Supraventricular</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hormones</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03243604
org study id: CIC1421-17-08
nct id: NCT03243604
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Abiraterone associated with prednisone is used in prostate cancer. Abiraterone is a selective
      small-molecule inhibiting cytochrome P450 17A1 (CYP17A1), a key enzyme in androgen synthesis.

      CYP17A inhibition is also responsible for mineral corticosteroid related adverse events as
      hypokaliemia, fluid retention, and hypertension. Primary hyperaldosteronism is associated
      with cardiovascular toxicities such as atrial fibrillation and cardiac failure. Other
      androgen-deprivation therapies are not associated with increased mineral corticosteroid
      level.

      This study investigates reports of cardiovascular toxicities for treatment including L02 (sex
      hormones used in treatment of neoplastic diseases), and G03 (sex hormones) used in prostate
      cancer in the French pharmacovigilance database and in the EudraCT database.
Due to its peculiar pharmacology, abiraterone is potentially associated with more
      cardiotoxicity as compared to other androgen-deprivation therapies. This study investigates
      the main characteristics of patients affected by cardiovascular side effects of which
      supraventricular arrhythmias (including atrial fibrillation, atrial flutter, supraventricular
      tachycardia), and cardiac failure imputed to drugs classified as L02, and G03 according to
      anatomical therapeutic chemical (ATC) classification. A causality assessment according to the
      World Health Organization-The Uppsala Monitoring Centre (WHO-UMC) is systematically applied.
observational model: Case-Only
time perspective: Retrospective
measure: Analysis of disproportionality of reports for cardiotoxicity associated with abiraterone as compared to enzalutamide by performing a case- non-case study
time frame: 2 months
description: Analysis of disproportionality of reports for cardiotoxicity associated with abiraterone as compared to enzalutamide by performing a case- non-case study
measure: Compare the reporting of suspected drug-induced supraventricular arrhythmias with abiraterone as compared to enzalutamide by performing a disproportionality analysis
time frame: 2 months
description: Compare the reporting of suspected drug-induced supraventricular arrhythmias with abiraterone as compared to enzalutamide by performing a disproportionality analysis
measure: Compare the reporting of drug-induced cardiac failure with abiraterone as compared to enzalutamide by performing a disproportionality analysis
time frame: 2 months
description: Compare the reporting of drug-induced cardiac failure with abiraterone as compared to enzalutamide by performing a disproportionality analysis
measure: Compare the reporting of drug-induced cardiac failure and/or supraventricular arrhythmias with abiraterone as compared to other androgen-deprivation therapies by performing a disproportionality analysis
time frame: 2 months
description: Compare the reporting of drug-induced cardiac failure and/or supraventricular arrhythmias with abiraterone as compared to other androgen-deprivation therapies by performing a disproportionality analysis
measure: Description of other mineralocorticoid related adverse events (hypokaliemia, fluid retention, and hypertension) when the cardio toxicity occurs
time frame: 2 months
description: Description of other mineralocorticoid related adverse events (hypokaliemia, fluid retention, and hypertension) when the cardio toxicity occurs
measure: Description of the population of patients having a cardio-vascular adverse event
time frame: 2 months
description: Description of the population of patients having a cardio-vascular adverse event
measure: Description of the duration of treatment when the toxicity happens (role of cumulative dose)
time frame: 2 months
description: Description of the duration of treatment when the toxicity happens (role of cumulative dose)
measure: Description of the drug-drug interactions associated with adverse events
time frame: 2 months
description: Description of the drug-drug interactions associated with adverse events
measure: Causality assessment of reported cardiovascular events according to the WHO-UMC system
time frame: 2 months
description: Causality assessment of reported cardiovascular events according to the WHO-UMC system
intervention type: Drug
intervention name: L02 (sex hormones used in treatment of neoplastic diseases) and G03 (sex hormones)
description: Androgen-deprivation therapies including L02 (sex hormones used in treatment of neoplastic diseases), and G03 (sex hormones)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Male
gender based: Yes
gender description: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: France
responsible party type: Principal Investigator
investigator affiliation: Groupe Hospitalier Pitie-Salpetriere
investigator full name: Joe Elie Salem
investigator title: MD, PhD
mesh term: Atrial Fibrillation
mesh term: Arrhythmias, Cardiac
mesh term: Tachycardia
mesh term: Cardiotoxicity
mesh term: Heart Failure
mesh term: Tachycardia, Supraventricular
mesh term: Hormones