xml: <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/NCT05972785</url>
    </required_header>
    <id_info>
      <org_study_id>2014896</org_study_id>
      <nct_id>NCT05972785</nct_id>
    </id_info>
    <brief_title>Long-term Use of CCB and Breast Cancer Risk</brief_title>
    <official_title>Association of Long-term Use of Calcium Channel Blockers (CCB) and Risk of Breast Cancer: A Retrospective Longitudinal Observational Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Curtin University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Curtin University</source>
    <brief_summary>
      <textblock>
        The goal of this retrospective observational study is to examine whether long-term calcium&#xD;
        channel blocker (CCB) use is associated with the development of breast cancer amongst women&#xD;
        enrolled in three longitudinal cohort studies in Australia and the Netherlands . The main&#xD;
        questions it aims to answer are:&#xD;
  &#xD;
          -  Is long-term CCB use associated with the development of breast cancer amongst women&#xD;
             enrolled in three longitudinal cohort studies in Australia and the Netherlands and what&#xD;
             is the dose-response nature of this association.&#xD;
  &#xD;
          -  Does differences in the association between calcium channel blocker use and the&#xD;
             development of breast cancer exist between Australian and Dutch women.&#xD;
  &#xD;
        The investigators will utilise data from the Australian Longitudinal Study on Women's Health&#xD;
        (ALSWH) , 45 and Up Study and Rotterdam study.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Aims: To examine the association between long-term calcium channel blocker (CCB) use and the&#xD;
        development of breast cancer.&#xD;
  &#xD;
        Data sources: the Australian Longitudinal Study on Women's Health , 45 and Up Study,&#xD;
        Rotterdam study and linked administrative data.&#xD;
  &#xD;
        Study cohort: Women with self-reported hypertension (HTN) without prior breast cancer.&#xD;
  &#xD;
        Harmonisation: Relevant variables will be checked for harmonisation in which variables&#xD;
        available in all three cohort will be used in the harmonised analysis. The variables will be&#xD;
        checked on the definition, measurement and harmonisation rules. Variables that cannot be&#xD;
        harmonised across the cohorts will be used in the cohort specific analyses.&#xD;
  &#xD;
        Exposure measurement: The primary exposure is the use of CCB, which will be identified by the&#xD;
        anatomical therapeutic chemical code (C08) in the medicine data. Exposure to CCB as well as&#xD;
        other antihypertensive (AHT) medicines will be captured separately as the cumulative&#xD;
        dose-duration of exposure during follow up. Participants will be stratified in four groups:&#xD;
        women with HTN with no AHT use, women with HTN exposed to CCB only, women with HTN exposed to&#xD;
        non-CCB and women with HTN exposed to both CCB and non-CCB.&#xD;
  &#xD;
        Outcome measurement: Data on a diagnosis of invasive breast cancer will be obtained from&#xD;
        cancer registries and hospital admission data using ICD-10 code of C50.x.&#xD;
  &#xD;
        Potential confounders: age, education, marital status, socioeconomic status, body mass index,&#xD;
        diabetes, heart disease, stroke, age when had first child, parity, history of hysterectomy or&#xD;
        oophorectomy, use of hormonal contraception, use of hormonal replacement therapy.&#xD;
  &#xD;
        Statistical analysis: The association between CCB use and breast cancer risk will be&#xD;
        estimated by the Fine and Gray competing risk regression model in which a first diagnosis of&#xD;
        invasive breast cancer will be treated as the principle event and death and bilateral&#xD;
        mastectomy (without a diagnosis of breast cancer) will be competing risks. The nonlinear&#xD;
        threshold models will be used to capture any differential effect of the cumulative&#xD;
        dose-duration of CCB while simultaneously accounting for the cumulative dose-duration of&#xD;
        other AHT exposure on breast cancer risk. Other confounders will be accounted for in the&#xD;
        models using propensity scores.&#xD;
  &#xD;
        Implications: Results from this study will contribute to addressing the concerns about using&#xD;
        CCB for hypertension treatment in women, particularly in those who have high risk of breast&#xD;
        cancer.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Active, not recruiting</overall_status>
    <start_date type="Actual">July 1, 2022</start_date>
    <completion_date type="Anticipated">December 2025</completion_date>
    <primary_completion_date type="Anticipated">June 30, 2025</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>Incident rate of invasive breast cancer</measure>
      <time_frame>From cohort entry until the earliest date of one of the following: a diagnosis of invasive breast cancer, bilateral mastectomy (without breast cancer) or death, assessed up to 14 years.</time_frame>
      <description>The outcome will be defined based on the ICD-10 code of C50.x (malignant neoplasm of breast).</description>
    </primary_outcome>
    <number_of_groups>4</number_of_groups>
    <enrollment type="Anticipated">68500</enrollment>
    <condition>Hypertension,Essential</condition>
    <condition>Breast Cancer</condition>
    <arm_group>
      <arm_group_label>No AHT</arm_group_label>
      <description>Women with HTN with no AHT use</description>
    </arm_group>
    <arm_group>
      <arm_group_label>AHT but non-CCB</arm_group_label>
      <description>Women with HTN exposed to other antihypertensive medicines but not exposed to calcium channel blockers</description>
    </arm_group>
    <arm_group>
      <arm_group_label>CCB only</arm_group_label>
      <description>Women with HTN exposed to calcium channel blockers but not exposed to other antihypertensive medicines</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Both CCB and non-CCB</arm_group_label>
      <description>Women with HTN exposed to both calcium channel blockers and other antihypertensive medicines.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Calcium channel blocker</intervention_name>
      <description>Drugs with ATC code C08 will be categorised as calcium channel blockers.</description>
      <arm_group_label>Both CCB and non-CCB</arm_group_label>
      <arm_group_label>CCB only</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Beta blocker</intervention_name>
      <description>Drugs with ATC code C07 will be categorised as beta-blockers.</description>
      <arm_group_label>AHT but non-CCB</arm_group_label>
      <arm_group_label>Both CCB and non-CCB</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Diuretic</intervention_name>
      <description>Drugs with ATC code C03 will be categorised as diuretics.</description>
      <arm_group_label>AHT but non-CCB</arm_group_label>
      <arm_group_label>Both CCB and non-CCB</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>RAS</intervention_name>
      <description>Drugs with ATC code C09 will be categorised as RAS (agents acting on the renin angiotensin system).</description>
      <arm_group_label>AHT but non-CCB</arm_group_label>
      <arm_group_label>Both CCB and non-CCB</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Other AHT</intervention_name>
      <description>Drugs with ATC code C02 will be categorised as other antihypertensives.</description>
      <arm_group_label>AHT but non-CCB</arm_group_label>
      <arm_group_label>Both CCB and non-CCB</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>None AHT</intervention_name>
      <description>None AHT</description>
      <arm_group_label>No AHT</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          The study will include eligible women enrolled in three longitudinal cohorts: ALSWH, 45 and&#xD;
          Up Study and the Rotterdam study.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion criteria:&#xD;
  &#xD;
            -  Alive and still enrolled in the longitudinal cohort at the study entry (2004 to 2009)&#xD;
  &#xD;
            -  Self-reported/diagnosed hypertension at study entry.&#xD;
  &#xD;
          Exclusion criteria:&#xD;
  &#xD;
          + A history of breast cancer.&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <minimum_age>45 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
    </eligibility>
    <location>
      <facility>
        <name>Curtin university</name>
        <address>
          <city>Bentley</city>
          <state>Western Australia</state>
          <zip>6102</zip>
          <country>Australia</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Australia</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 24, 2023</study_first_submitted>
    <study_first_submitted_qc>August 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 2, 2023</study_first_posted>
    <last_update_submitted>August 1, 2023</last_update_submitted>
    <last_update_submitted_qc>August 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 2, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Curtin University</investigator_affiliation>
      <investigator_full_name>Rachael Moorin</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Breast Neoplasms</mesh_term>
      <mesh_term>Essential Hypertension</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Calcium Channel Blockers</mesh_term>
      <mesh_term>Calcium</mesh_term>
      <mesh_term>Diuretics</mesh_term>
      <mesh_term>Adrenergic beta-Antagonists</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05972785
  org study id: 2014896
  nct id: NCT05972785
  lead sponsor: 
  The goal of this retrospective observational study is to examine whether long-term calcium
        channel blocker (CCB) use is associated with the development of breast cancer amongst women
        enrolled in three longitudinal cohort studies in Australia and the Netherlands . The main
        questions it aims to answer are:
  
          -  Is long-term CCB use associated with the development of breast cancer amongst women
             enrolled in three longitudinal cohort studies in Australia and the Netherlands and what
             is the dose-response nature of this association.
  
          -  Does differences in the association between calcium channel blocker use and the
             development of breast cancer exist between Australian and Dutch women.
  
        The investigators will utilise data from the Australian Longitudinal Study on Women's Health
        (ALSWH) , 45 and Up Study and Rotterdam study.
  Aims: To examine the association between long-term calcium channel blocker (CCB) use and the
        development of breast cancer.
  
        Data sources: the Australian Longitudinal Study on Women's Health , 45 and Up Study,
        Rotterdam study and linked administrative data.
  
        Study cohort: Women with self-reported hypertension (HTN) without prior breast cancer.
  
        Harmonisation: Relevant variables will be checked for harmonisation in which variables
        available in all three cohort will be used in the harmonised analysis. The variables will be
        checked on the definition, measurement and harmonisation rules. Variables that cannot be
        harmonised across the cohorts will be used in the cohort specific analyses.
  
        Exposure measurement: The primary exposure is the use of CCB, which will be identified by the
        anatomical therapeutic chemical code (C08) in the medicine data. Exposure to CCB as well as
        other antihypertensive (AHT) medicines will be captured separately as the cumulative
        dose-duration of exposure during follow up. Participants will be stratified in four groups:
        women with HTN with no AHT use, women with HTN exposed to CCB only, women with HTN exposed to
        non-CCB and women with HTN exposed to both CCB and non-CCB.
  
        Outcome measurement: Data on a diagnosis of invasive breast cancer will be obtained from
        cancer registries and hospital admission data using ICD-10 code of C50.x.
  
        Potential confounders: age, education, marital status, socioeconomic status, body mass index,
        diabetes, heart disease, stroke, age when had first child, parity, history of hysterectomy or
        oophorectomy, use of hormonal contraception, use of hormonal replacement therapy.
  
        Statistical analysis: The association between CCB use and breast cancer risk will be
        estimated by the Fine and Gray competing risk regression model in which a first diagnosis of
        invasive breast cancer will be treated as the principle event and death and bilateral
        mastectomy (without a diagnosis of breast cancer) will be competing risks. The nonlinear
        threshold models will be used to capture any differential effect of the cumulative
        dose-duration of CCB while simultaneously accounting for the cumulative dose-duration of
        other AHT exposure on breast cancer risk. Other confounders will be accounted for in the
        models using propensity scores.
  
        Implications: Results from this study will contribute to addressing the concerns about using
        CCB for hypertension treatment in women, particularly in those who have high risk of breast
        cancer.
  observational model: Cohort
  time perspective: Retrospective
  measure: Incident rate of invasive breast cancer
  time frame: From cohort entry until the earliest date of one of the following: a diagnosis of invasive breast cancer, bilateral mastectomy (without breast cancer) or death, assessed up to 14 years.
  description: The outcome will be defined based on the ICD-10 code of C50.x (malignant neoplasm of breast).
  arm group label: No AHT
  description: Women with HTN with no AHT use
  arm group label: AHT but non-CCB
  description: Women with HTN exposed to other antihypertensive medicines but not exposed to calcium channel blockers
  arm group label: CCB only
  description: Women with HTN exposed to calcium channel blockers but not exposed to other antihypertensive medicines
  arm group label: Both CCB and non-CCB
  description: Women with HTN exposed to both calcium channel blockers and other antihypertensive medicines.
  intervention type: Drug
  intervention name: Calcium channel blocker
  description: Drugs with ATC code C08 will be categorised as calcium channel blockers.
  arm group label: Both CCB and non-CCB
  arm group label: CCB only
  intervention type: Drug
  intervention name: Beta blocker
  description: Drugs with ATC code C07 will be categorised as beta-blockers.
  arm group label: AHT but non-CCB
  arm group label: Both CCB and non-CCB
  intervention type: Drug
  intervention name: Diuretic
  description: Drugs with ATC code C03 will be categorised as diuretics.
  arm group label: AHT but non-CCB
  arm group label: Both CCB and non-CCB
  intervention type: Drug
  intervention name: RAS
  description: Drugs with ATC code C09 will be categorised as RAS (agents acting on the renin angiotensin system).
  arm group label: AHT but non-CCB
  arm group label: Both CCB and non-CCB
  intervention type: Drug
  intervention name: Other AHT
  description: Drugs with ATC code C02 will be categorised as other antihypertensives.
  arm group label: AHT but non-CCB
  arm group label: Both CCB and non-CCB
  intervention type: Drug
  intervention name: None AHT
  description: None AHT
  arm group label: No AHT
  study pop: 
  sampling method: Probability Sample
  criteria: 
  gender: Female
  minimum age: 45 Years
  maximum age: N/A
  facility: 
  country: Australia
  responsible party type: Principal Investigator
  investigator affiliation: Curtin University
  investigator full name: Rachael Moorin
  investigator title: Professor
  mesh term: Breast Neoplasms
  mesh term: Essential Hypertension
  mesh term: Calcium Channel Blockers
  mesh term: Calcium
  mesh term: Diuretics
  mesh term: Adrenergic beta-Antagonists
  sharing ipd: No