<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/NCT03290287</url>
  </required_header>
  <id_info>
    <org_study_id>D6560R00004</org_study_id>
    <secondary_id>EUPAS13616</secondary_id>
    <nct_id>NCT03290287</nct_id>
  </id_info>
  <brief_title>Aclidinium Bromide Post-Authorisation Safety Study to Evaluate the Risk of Cardiovascular Endpoints</brief_title>
  <acronym>PASS</acronym>
  <official_title>Aclidinium Bromide Post-Authorisation Safety Study to Evaluate the Risk of Cardiovascular Endpoints: Common Study Protocol</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>RTI Health Solutions</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>AstraZeneca</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the potential cardiovascular safety concerns and&#xD;
      all-cause mortality described in the risk management plan for aclidinium bromide, through&#xD;
      sequential, nested case-control studies for each endpoint of interest&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a post-authorisation safety study (PASS) of new users of aclidinium bromide, fixed&#xD;
      dose aclidinium bromide/formoterol fumarate dihydrate, and other inhaled medications&#xD;
      frequently used by patients with COPD&#xD;
&#xD;
      The plan is for the PASS study to be conducted on one population-based automated health&#xD;
      database; the initial candidate database is the CRPD in the United Kingdom.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 1, 2017</start_date>
  <completion_date type="Actual">June 30, 2022</completion_date>
  <primary_completion_date type="Actual">June 30, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence rate of mortality from all causes</measure>
    <time_frame>From the launch of Aclidinium Bromide in the UK (October 2012) to the end of the study period (2-3 months following start of data collection [January 2017]).</time_frame>
    <description>Age- and sex-standardised incidence rate per 1,000 person-years (95% CI). Potential cases will be identified by general practitioner diagnosis, hospital discharge codes and mortality data from national statistics.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence rate of first-ever hospitalisation for heart failure</measure>
    <time_frame>From the launch of Aclidinium Bromide in the UK (October 2012) to the end of the study period (2-3 months following start of data collection [First semester 2017]).</time_frame>
    <description>Age- and sex-standardised incidence rate per 1,000 person-years (95% CI). Potential cases will be identified by general practitioner diagnosis, hospital discharge codes and mortality data from national statistics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence rate of hospitalisation for acute myocardial infarction (fatal or non-fatal)</measure>
    <time_frame>From the launch of Aclidinium Bromide in the UK (October 2012) to the end of the study period (2-3 months following start of data collection [First semester 2021]).</time_frame>
    <description>Including community (out-of-hospital) coronary heart disease deaths. Age- and sex-standardised incidence rate per 1,000 person-years (95% CI). Potential cases will be identified by general practitioner diagnosis, hospital discharge codes and mortality data from national statistics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence rate of acute stroke (fatal or non-fatal)</measure>
    <time_frame>From the launch of Aclidinium Bromide in the UK (October 2012) to the end of the study period (2-3 months following start of data collection [First semester 2020]).</time_frame>
    <description>Including community (out-of-hospital) cerebrovascular disease deaths. Age- and sex-standardised incidence rate per 1,000 person-years (95% CI). Potential cases will be identified by general practitioner diagnosis, hospital discharge codes and mortality data from national statistics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence rate of new episodes of any type of diagnosed cardiac arrhythmia</measure>
    <time_frame>From the launch of Aclidinium Bromide in the UK (October 2012) to the end of the study period (2-3 months following start of data collection [First semester 2022]).</time_frame>
    <description>Age- and sex-standardised incidence rate per 1,000 person-years (95% CI). Potential cases will be identified by general practitioner diagnosis, hospital discharge codes and mortality data from national statistics.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Relative risk of acute myocardial infarction, stroke, and out-of-hospital coronary heart disease or cerebrovascular death</measure>
    <time_frame>From the launch of Aclidinium Bromide in the UK (October 2012) to the end of the study period of individual components (2-3 months following start of data collection).</time_frame>
    <description>A composite endpoint of acute myocardial infarction, stroke, and out-of-hospital coronary heart disease or cerebrovascular death (if confirmed that the direction and magnitude of the risk is similar across the individual components). Potential cases will be identified by general practitioner diagnosis, hospital discharge codes and mortality data from national statistics.</description>
  </other_outcome>
  <other_outcome>
    <measure>Incidence rate of new episodes of atrial fibrillation or flutter</measure>
    <time_frame>From the launch of Aclidinium Bromide in the UK (October 2012) to the end of the study period (2-3 months following start of data collection [First semester 2022]).</time_frame>
    <description>Including episodes of paroxysmal (intermittent) atrial fibrillation or a new episode (first ever) or atrial fibrillation in patients without atrial fibrillation or flutter. Age- and sex-standardised incidence rate per 1,000 person-years (95% CI). Potential cases will be identified by general practitioner diagnosis, hospital discharge codes and mortality data from national statistics.</description>
  </other_outcome>
  <other_outcome>
    <measure>Incidence rate of new episodes of serious ventricular arrhythmias (SVA)</measure>
    <time_frame>From the launch of Aclidinium Bromide in the UK (October 2012) to the end of the study period (2-3 months following start of data collection [First semester 2022]).</time_frame>
    <description>Age- and sex-standardised incidence rate per 1,000 person-years (95% CI). Potential cases will be identified by general practitioner diagnosis, hospital discharge codes and mortality data from national statistics.</description>
  </other_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">26839</enrollment>
  <condition>Pulmonary Disease, Chronic Obstructive</condition>
  <arm_group>
    <arm_group_label>New users of aclidinium bromide</arm_group_label>
    <description>This nested cohort will be composed of patients aged 40 years or older who have previously been diagnosed with COPD and who are new users of aclidinium bromide (monotherapy; concomitant with formoterol not in fixed-dose combination; and aclidinium/formoterol)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>New users of other COPD medication</arm_group_label>
    <description>This nested cohort will include patients aged 40 years or older who have previously been diagnosed with COPD and who are new users of other COPD medication: tiotropium, other LAMAs, LABA, LABA/ICS and LAMA/LABA.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aclidinium bromide</intervention_name>
    <description>Administered as monotherapy, concomitant with formoterol not in fixed-dose combination, or fixed-dose aclidinium/formoterol</description>
    <arm_group_label>New users of aclidinium bromide</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Other COPD medication</intervention_name>
    <description>Users of the following COPD medications:&#xD;
Tiotropium&#xD;
Other long-acting anticholinergic (LAMAs): glycopyrronium bromide, umeclidinium&#xD;
LABA: formoterol, salmeterol, indacaterol&#xD;
LABA/ICS (LABA in fixed-dose combinations with ICS): formoterol/budesonide, formoterol/beclometasone, formoterol/mometasone, formoterol/fluticasone, salmeterol/fluticasone, and vilanterol/fluticasone.&#xD;
LAMA/LABA (approved or under regulatory review or in development): glycopyrrolate/formoterol, glycopyrronium/indacaterol, tiotropium/olodaterol, umeclidinium/vilanterol</description>
    <arm_group_label>New users of other COPD medication</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        The study will be conducted in patients aged 40 years or older diagnosed with COPD&#xD;
        initiating treatment with aclidinium bromide or other inhaled COPD treatments. Patients&#xD;
        must have at least 1 year of enrolment in the electronic database and to have not been&#xD;
        prescribed the study medication of interest during the 6-months before the date of the&#xD;
        first prescription for that specific study medication. Patients with life-threatening&#xD;
        non-cardiovascular comorbidity (e.g., malignancy, HIV infection, other) will be excluded&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Have at least 1 year of enrolment in the electronic database. In the CPRD, only&#xD;
             patients with permanent registration status in &quot;up to standard&quot; participant general&#xD;
             practices will be included in the cohort.&#xD;
&#xD;
          2. Be aged 40 years or older.&#xD;
&#xD;
          3. Have a recorded diagnosis of COPD.&#xD;
&#xD;
          4. Have not been prescribed a study medication of interest during the 6 months before the&#xD;
             date of the first prescription for that specific study medication.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with cancer or other serious, non-cardiovascular, life-threatening conditions&#xD;
             or indicators of severe comorbidity will be excluded from the study cohort.&#xD;
&#xD;
          2. Subjects who will be potentially excluded are those with the following conditions&#xD;
             recorded in the database at any time before the date of cohort entry: cancer, HIV,&#xD;
             respiratory failure, end-stage renal disease or dialysis, organ transplantation, drug&#xD;
             or alcohol abuse, coma, congenital abnormalities of the heart or great arteries.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Clinical Practice Research Datalink</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>August 18, 2017</study_first_submitted>
  <study_first_submitted_qc>September 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 21, 2017</study_first_posted>
  <last_update_submitted>January 30, 2023</last_update_submitted>
  <last_update_submitted_qc>January 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 31, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COPD</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bromides</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/NCT03290287
org study id: D6560R00004
secondary id: EUPAS13616
nct id: NCT03290287
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to evaluate the potential cardiovascular safety concerns and
      all-cause mortality described in the risk management plan for aclidinium bromide, through
      sequential, nested case-control studies for each endpoint of interest
This is a post-authorisation safety study (PASS) of new users of aclidinium bromide, fixed
      dose aclidinium bromide/formoterol fumarate dihydrate, and other inhaled medications
      frequently used by patients with COPD

      The plan is for the PASS study to be conducted on one population-based automated health
      database; the initial candidate database is the CRPD in the United Kingdom.
observational model: Case-Control
time perspective: Prospective
measure: Incidence rate of mortality from all causes
time frame: From the launch of Aclidinium Bromide in the UK (October 2012) to the end of the study period (2-3 months following start of data collection [January 2017]).
description: Age- and sex-standardised incidence rate per 1,000 person-years (95% CI). Potential cases will be identified by general practitioner diagnosis, hospital discharge codes and mortality data from national statistics.
measure: Incidence rate of first-ever hospitalisation for heart failure
time frame: From the launch of Aclidinium Bromide in the UK (October 2012) to the end of the study period (2-3 months following start of data collection [First semester 2017]).
description: Age- and sex-standardised incidence rate per 1,000 person-years (95% CI). Potential cases will be identified by general practitioner diagnosis, hospital discharge codes and mortality data from national statistics.
measure: Incidence rate of hospitalisation for acute myocardial infarction (fatal or non-fatal)
time frame: From the launch of Aclidinium Bromide in the UK (October 2012) to the end of the study period (2-3 months following start of data collection [First semester 2021]).
description: Including community (out-of-hospital) coronary heart disease deaths. Age- and sex-standardised incidence rate per 1,000 person-years (95% CI). Potential cases will be identified by general practitioner diagnosis, hospital discharge codes and mortality data from national statistics.
measure: Incidence rate of acute stroke (fatal or non-fatal)
time frame: From the launch of Aclidinium Bromide in the UK (October 2012) to the end of the study period (2-3 months following start of data collection [First semester 2020]).
description: Including community (out-of-hospital) cerebrovascular disease deaths. Age- and sex-standardised incidence rate per 1,000 person-years (95% CI). Potential cases will be identified by general practitioner diagnosis, hospital discharge codes and mortality data from national statistics.
measure: Incidence rate of new episodes of any type of diagnosed cardiac arrhythmia
time frame: From the launch of Aclidinium Bromide in the UK (October 2012) to the end of the study period (2-3 months following start of data collection [First semester 2022]).
description: Age- and sex-standardised incidence rate per 1,000 person-years (95% CI). Potential cases will be identified by general practitioner diagnosis, hospital discharge codes and mortality data from national statistics.
measure: Relative risk of acute myocardial infarction, stroke, and out-of-hospital coronary heart disease or cerebrovascular death
time frame: From the launch of Aclidinium Bromide in the UK (October 2012) to the end of the study period of individual components (2-3 months following start of data collection).
description: A composite endpoint of acute myocardial infarction, stroke, and out-of-hospital coronary heart disease or cerebrovascular death (if confirmed that the direction and magnitude of the risk is similar across the individual components). Potential cases will be identified by general practitioner diagnosis, hospital discharge codes and mortality data from national statistics.
measure: Incidence rate of new episodes of atrial fibrillation or flutter
time frame: From the launch of Aclidinium Bromide in the UK (October 2012) to the end of the study period (2-3 months following start of data collection [First semester 2022]).
description: Including episodes of paroxysmal (intermittent) atrial fibrillation or a new episode (first ever) or atrial fibrillation in patients without atrial fibrillation or flutter. Age- and sex-standardised incidence rate per 1,000 person-years (95% CI). Potential cases will be identified by general practitioner diagnosis, hospital discharge codes and mortality data from national statistics.
measure: Incidence rate of new episodes of serious ventricular arrhythmias (SVA)
time frame: From the launch of Aclidinium Bromide in the UK (October 2012) to the end of the study period (2-3 months following start of data collection [First semester 2022]).
description: Age- and sex-standardised incidence rate per 1,000 person-years (95% CI). Potential cases will be identified by general practitioner diagnosis, hospital discharge codes and mortality data from national statistics.
arm group label: New users of aclidinium bromide
description: This nested cohort will be composed of patients aged 40 years or older who have previously been diagnosed with COPD and who are new users of aclidinium bromide (monotherapy; concomitant with formoterol not in fixed-dose combination; and aclidinium/formoterol)
arm group label: New users of other COPD medication
description: This nested cohort will include patients aged 40 years or older who have previously been diagnosed with COPD and who are new users of other COPD medication: tiotropium, other LAMAs, LABA, LABA/ICS and LAMA/LABA.
intervention type: Drug
intervention name: Aclidinium bromide
description: Administered as monotherapy, concomitant with formoterol not in fixed-dose combination, or fixed-dose aclidinium/formoterol
arm group label: New users of aclidinium bromide
intervention type: Drug
intervention name: Other COPD medication
description: Users of the following COPD medications:
Tiotropium
Other long-acting anticholinergic (LAMAs): glycopyrronium bromide, umeclidinium
LABA: formoterol, salmeterol, indacaterol
LABA/ICS (LABA in fixed-dose combinations with ICS): formoterol/budesonide, formoterol/beclometasone, formoterol/mometasone, formoterol/fluticasone, salmeterol/fluticasone, and vilanterol/fluticasone.
LAMA/LABA (approved or under regulatory review or in development): glycopyrrolate/formoterol, glycopyrronium/indacaterol, tiotropium/olodaterol, umeclidinium/vilanterol
arm group label: New users of other COPD medication
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Bromides
sharing ipd: No