<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/NCT03249506</url>
  </required_header>
  <id_info>
    <org_study_id>CR108355</org_study_id>
    <secondary_id>RRA-17640</secondary_id>
    <nct_id>NCT03249506</nct_id>
  </id_info>
  <brief_title>Cardiovascular Outcomes in Participants With Type 2 Diabetes Mellitus (T2DM)</brief_title>
  <official_title>Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Janssen Research &amp; Development, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Janssen Research &amp; Development, LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to identify and evaluate the event rate of the composite&#xD;
      endpoint of all-cause mortality (ACM) or hospitalization for heart failure (HF) for&#xD;
      participants with Type 2 Diabetes mellitus (T2DM) and established cardiovascular (CV) disease&#xD;
      among new users of sodium-glucose co-transporter 2 inhibitor (SGLT2i) as compared with new&#xD;
      users of non-SGLT2i anti-hyperglycemic agent (AHA).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 12, 2016</start_date>
  <completion_date type="Actual">November 1, 2017</completion_date>
  <primary_completion_date type="Actual">November 1, 2017</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>Incidence Rate of the Composite of All-cause Mortality (ACM) or Hospitalization for Heart Failure (HF)</measure>
    <time_frame>approximately 3 years</time_frame>
    <description>Composite of ACM and hospitalization of HF will be assessed in participants with type 2 diabetes mellitus. ACM is defined as any record of death regardless of the cause of death and is identified through a master death file within the military health system (MHS) that compiles, processes, and validates all death records from the following data sources: inpatient hospitalization discharge dispositions from military and civilian hospitals, ambulatory and outpatient encounter records with recorded death disposition, casualty death feed related to active duty service member combat related deaths, survivor self-report, and an established, recurring social security death index (SSDI) feed from the social security administration. Hospitalization for HF will be defined as any inpatient hospitalization record, inclusive of both military and civilian hospitals, with an international classification of disease-9th or 10th edition (ICD-9/10) in the primary diagnosis field.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence Rate of All-Cause Mortality</measure>
    <time_frame>approximately 3 years</time_frame>
    <description>ACM is defined as any record of death regardless of the cause of death and is identified through a master death file within MHS that compiles, processes, and validates all death records from the following data sources: inpatient hospitalization discharge dispositions from military and civilian hospitals, ambulatory and outpatient encounter records with recorded death disposition, casualty death feed related to active duty service member combat related deaths, survivor self-report, and an established, recurring SSDI feed from the social security administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence Rate of Hospitalization for HF</measure>
    <time_frame>approximately 3 years</time_frame>
    <description>Hospitalization for HF will be defined as any inpatient hospitalization record, inclusive of both military and civilian hospitals, with an international classification of disease-9th or 10th edition (ICD-9/10) in the primary diagnosis field.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence Rate of Major Adverse Cardiovascular Events (MACE)</measure>
    <time_frame>approximately 3 years</time_frame>
    <description>MACE will be defined as the composite endpoint of ACM, non-fatal stroke, or non-fatal myocardial infarction (MI).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence Rate of Composite of MACE or Hospitalization for HF</measure>
    <time_frame>approximately 3 years</time_frame>
    <description>Participants for composite of ACM and hospitalization of HF will be assessed. MACE will be defined as the composite endpoint of ACM, non-fatal stroke, or non-fatal myocardial infarction (MI). Hospitalization for HF will be defined as any inpatient hospitalization record, inclusive of both military and civilian hospitals, with an international classification of disease-9th or 10th edition (ICD-9/10) in the primary diagnosis field.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence Rate of Non-fatal stroke</measure>
    <time_frame>approximately 3 years</time_frame>
    <description>Non-fatal stroke will be defined as any inpatient hospitalization record, inclusive of both military and civilian hospitals, with an ICD-9/10 in the primary diagnosis field pertaining to either ischemic stroke or hemorrhagic stroke and the participant did not die during the index hospitalization.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence Rate of Non-Fatal Myocardial Infarction</measure>
    <time_frame>approximately 3 years</time_frame>
    <description>Non-fatal MI will be defined as any inpatient hospitalization record, inclusive of both military and civilian hospitals, with an ICD-9/10 in the primary diagnosis field and the participant did not die during the index hospitalization.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Below Knee Lower Extremity (BKLE) Amputation</measure>
    <time_frame>approximately 3 years</time_frame>
    <description>The occurrence of a below-knee lower extremity amputation will be defined by observing an associated procedure code in the outpatient or inpatient medical service claims.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">25358</enrollment>
  <condition>Diabetes Mellitus, Type 2</condition>
  <arm_group>
    <arm_group_label>Cohort 1: Non-SGLT2i new Users</arm_group_label>
    <description>This is a retrospective cohort study identifying participants with type 2 diabetes mellitus (T2DM) and established cardiovascular (CV) disease using the Military Health System (MHS) over a 3-year period. Cohort 1 included participants with incident exposure of one or more non-sodium glucose co-transporter 2 inhibitor (SGLT2i) anti-hyperglycemic agent (AHA) therapy during the study period with no prior or subsequent SGLT2i exposure throughout the study period. New users are defined as participants whose first exposure to any non-metformin AHA medication occurs greater than or equal to (&gt;=) 365 days after their start of observation in the database with no prior exposure to any medication within the same AHA medication class in the prior 365 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2: SGLT2i new Users</arm_group_label>
    <description>Cohort 2 included participants with incident SGLT2i exposure during the study period regardless of prior or concurrent exposure to one or more additional AHA therapy. New users are defined as participants whose first exposure to SGLT2i medication occurs &gt;= 365 days after their start of observation in the database with no prior exposure to the same AHA medication class in the prior 365 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Canagliflozin</intervention_name>
    <description>Participants who received canagliflozin as a part of routine clinical practice and met new user criteria, will be included in SGLT2i new user group.</description>
    <arm_group_label>Cohort 2: SGLT2i new Users</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Empagliflozin</intervention_name>
    <description>Participants who received empagliflozin as a part of routine clinical practice and met new user criteria, will be included in SGLT2i new user group.</description>
    <arm_group_label>Cohort 2: SGLT2i new Users</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dapagliflozin</intervention_name>
    <description>Participants who received dapagliflozin as a part of routine clinical practice and met new user criteria, will be included in SGLT2i new user group.</description>
    <arm_group_label>Cohort 2: SGLT2i new Users</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dipeptidyl Peptidase-4 Inhibitor (DPP-4)</intervention_name>
    <description>Participants who received a DPP-4 as a part of routine clinical practice and met new user criteria, will be included in non-SGLT2i new users group.</description>
    <arm_group_label>Cohort 1: Non-SGLT2i new Users</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Glucagon-Like Peptide-1 Agonist (GLP-1)</intervention_name>
    <description>Participants who received a GLP-1 as a part of routine clinical practice and met new user criteria, will be included in non-SGLT2i new users group.</description>
    <arm_group_label>Cohort 1: Non-SGLT2i new Users</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Thiazolidinedione (TZD)</intervention_name>
    <description>Participants who received a TZD as a part of routine clinical practice and met new user criteria, will be included in non-SGLT2i new users group.</description>
    <arm_group_label>Cohort 1: Non-SGLT2i new Users</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sulfonylureas</intervention_name>
    <description>Participants who received a sulfonylureas as a part of routine clinical practice and met new user criteria, will be included in non-SGLT2i new users group.</description>
    <arm_group_label>Cohort 1: Non-SGLT2i new Users</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Insulin</intervention_name>
    <description>Participants who received a insulin as a part of routine clinical practice and met new user criteria, will be included in non-SGLT2i new users group.</description>
    <arm_group_label>Cohort 1: Non-SGLT2i new Users</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Participants diagnosed with type 2 diabetes mellitus (T2DM) and established cardiovascular&#xD;
        (CV) disease using the military health system (MHS) over a 3-year period (4/01/2013 to&#xD;
        3/31/2016) will be observed for the cardiovascular outcomes.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Type 2 diabetes mellitus (T2DM), defined as: greater than or equal to (&gt;=) 1&#xD;
             anti-hyperglycemic agent (AHA) medication in the study period, and; &gt;=1 diagnosis of&#xD;
             T2DM in any available diagnosis field on or prior to index&#xD;
&#xD;
          -  Established cardiovascular disease, defined as &gt;=1 diagnosis in any diagnosis field&#xD;
             for any of the following conditions: cerebrovascular disease; coronary artery disease&#xD;
             (including heart failure [HF]); peripheral artery disease&#xD;
&#xD;
          -  &gt;=1-year pre-index continuous eligibility; enrollment gaps of less than or equal to&#xD;
             (&lt;=) 30 days will be considered continuous enrollment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Type 1 Diabetes mellitus (T1DM) diagnosis on or prior to the index date&#xD;
&#xD;
          -  Secondary diabetes mellitus (DM) on or prior to the index date&#xD;
&#xD;
          -  Missing sex data&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Janssen Research &amp; Development, LLC Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Janssen Research &amp; Development, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Health ResearchTx, LLC</name>
      <address>
        <city>Trevose</city>
        <state>Pennsylvania</state>
        <zip>19053</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>August 11, 2017</study_first_submitted>
  <study_first_submitted_qc>August 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <last_update_submitted>November 17, 2017</last_update_submitted>
  <last_update_submitted_qc>November 17, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">November 21, 2017</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>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dapagliflozin</mesh_term>
    <mesh_term>Empagliflozin</mesh_term>
    <mesh_term>Canagliflozin</mesh_term>
    <mesh_term>2,4-thiazolidinedione</mesh_term>
    <mesh_term>Dipeptidyl-Peptidase IV Inhibitors</mesh_term>
    <mesh_term>Glucagon</mesh_term>
    <mesh_term>Glucagon-Like Peptide 1</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/NCT03249506
org study id: CR108355
secondary id: RRA-17640
nct id: NCT03249506
lead sponsor: 
has dmc: No
is fda regulated device: No
The purpose of this study is to identify and evaluate the event rate of the composite
      endpoint of all-cause mortality (ACM) or hospitalization for heart failure (HF) for
      participants with Type 2 Diabetes mellitus (T2DM) and established cardiovascular (CV) disease
      among new users of sodium-glucose co-transporter 2 inhibitor (SGLT2i) as compared with new
      users of non-SGLT2i anti-hyperglycemic agent (AHA).
observational model: Cohort
time perspective: Retrospective
measure: Incidence Rate of the Composite of All-cause Mortality (ACM) or Hospitalization for Heart Failure (HF)
time frame: approximately 3 years
description: Composite of ACM and hospitalization of HF will be assessed in participants with type 2 diabetes mellitus. ACM is defined as any record of death regardless of the cause of death and is identified through a master death file within the military health system (MHS) that compiles, processes, and validates all death records from the following data sources: inpatient hospitalization discharge dispositions from military and civilian hospitals, ambulatory and outpatient encounter records with recorded death disposition, casualty death feed related to active duty service member combat related deaths, survivor self-report, and an established, recurring social security death index (SSDI) feed from the social security administration. Hospitalization for HF will be defined as any inpatient hospitalization record, inclusive of both military and civilian hospitals, with an international classification of disease-9th or 10th edition (ICD-9/10) in the primary diagnosis field.
measure: Incidence Rate of All-Cause Mortality
time frame: approximately 3 years
description: ACM is defined as any record of death regardless of the cause of death and is identified through a master death file within MHS that compiles, processes, and validates all death records from the following data sources: inpatient hospitalization discharge dispositions from military and civilian hospitals, ambulatory and outpatient encounter records with recorded death disposition, casualty death feed related to active duty service member combat related deaths, survivor self-report, and an established, recurring SSDI feed from the social security administration.
measure: Incidence Rate of Hospitalization for HF
time frame: approximately 3 years
description: Hospitalization for HF will be defined as any inpatient hospitalization record, inclusive of both military and civilian hospitals, with an international classification of disease-9th or 10th edition (ICD-9/10) in the primary diagnosis field.
measure: Incidence Rate of Major Adverse Cardiovascular Events (MACE)
time frame: approximately 3 years
description: MACE will be defined as the composite endpoint of ACM, non-fatal stroke, or non-fatal myocardial infarction (MI).
measure: Incidence Rate of Composite of MACE or Hospitalization for HF
time frame: approximately 3 years
description: Participants for composite of ACM and hospitalization of HF will be assessed. MACE will be defined as the composite endpoint of ACM, non-fatal stroke, or non-fatal myocardial infarction (MI). Hospitalization for HF will be defined as any inpatient hospitalization record, inclusive of both military and civilian hospitals, with an international classification of disease-9th or 10th edition (ICD-9/10) in the primary diagnosis field.
measure: Incidence Rate of Non-fatal stroke
time frame: approximately 3 years
description: Non-fatal stroke will be defined as any inpatient hospitalization record, inclusive of both military and civilian hospitals, with an ICD-9/10 in the primary diagnosis field pertaining to either ischemic stroke or hemorrhagic stroke and the participant did not die during the index hospitalization.
measure: Incidence Rate of Non-Fatal Myocardial Infarction
time frame: approximately 3 years
description: Non-fatal MI will be defined as any inpatient hospitalization record, inclusive of both military and civilian hospitals, with an ICD-9/10 in the primary diagnosis field and the participant did not die during the index hospitalization.
measure: Percentage of Participants With Below Knee Lower Extremity (BKLE) Amputation
time frame: approximately 3 years
description: The occurrence of a below-knee lower extremity amputation will be defined by observing an associated procedure code in the outpatient or inpatient medical service claims.
arm group label: Cohort 1: Non-SGLT2i new Users
description: This is a retrospective cohort study identifying participants with type 2 diabetes mellitus (T2DM) and established cardiovascular (CV) disease using the Military Health System (MHS) over a 3-year period. Cohort 1 included participants with incident exposure of one or more non-sodium glucose co-transporter 2 inhibitor (SGLT2i) anti-hyperglycemic agent (AHA) therapy during the study period with no prior or subsequent SGLT2i exposure throughout the study period. New users are defined as participants whose first exposure to any non-metformin AHA medication occurs greater than or equal to (>=) 365 days after their start of observation in the database with no prior exposure to any medication within the same AHA medication class in the prior 365 days.
arm group label: Cohort 2: SGLT2i new Users
description: Cohort 2 included participants with incident SGLT2i exposure during the study period regardless of prior or concurrent exposure to one or more additional AHA therapy. New users are defined as participants whose first exposure to SGLT2i medication occurs >= 365 days after their start of observation in the database with no prior exposure to the same AHA medication class in the prior 365 days.
intervention type: Drug
intervention name: Canagliflozin
description: Participants who received canagliflozin as a part of routine clinical practice and met new user criteria, will be included in SGLT2i new user group.
arm group label: Cohort 2: SGLT2i new Users
intervention type: Drug
intervention name: Empagliflozin
description: Participants who received empagliflozin as a part of routine clinical practice and met new user criteria, will be included in SGLT2i new user group.
arm group label: Cohort 2: SGLT2i new Users
intervention type: Drug
intervention name: Dapagliflozin
description: Participants who received dapagliflozin as a part of routine clinical practice and met new user criteria, will be included in SGLT2i new user group.
arm group label: Cohort 2: SGLT2i new Users
intervention type: Drug
intervention name: Dipeptidyl Peptidase-4 Inhibitor (DPP-4)
description: Participants who received a DPP-4 as a part of routine clinical practice and met new user criteria, will be included in non-SGLT2i new users group.
arm group label: Cohort 1: Non-SGLT2i new Users
intervention type: Drug
intervention name: Glucagon-Like Peptide-1 Agonist (GLP-1)
description: Participants who received a GLP-1 as a part of routine clinical practice and met new user criteria, will be included in non-SGLT2i new users group.
arm group label: Cohort 1: Non-SGLT2i new Users
intervention type: Drug
intervention name: Thiazolidinedione (TZD)
description: Participants who received a TZD as a part of routine clinical practice and met new user criteria, will be included in non-SGLT2i new users group.
arm group label: Cohort 1: Non-SGLT2i new Users
intervention type: Drug
intervention name: Sulfonylureas
description: Participants who received a sulfonylureas as a part of routine clinical practice and met new user criteria, will be included in non-SGLT2i new users group.
arm group label: Cohort 1: Non-SGLT2i new Users
intervention type: Drug
intervention name: Insulin
description: Participants who received a insulin as a part of routine clinical practice and met new user criteria, will be included in non-SGLT2i new users group.
arm group label: Cohort 1: Non-SGLT2i new Users
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Janssen Research & Development, LLC Clinical Trial
role: Study Director
affiliation: Janssen Research & Development, LLC
facility: 
country: United States
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Dapagliflozin
mesh term: Empagliflozin
mesh term: Canagliflozin
mesh term: 2,4-thiazolidinedione
mesh term: Dipeptidyl-Peptidase IV Inhibitors
mesh term: Glucagon
mesh term: Glucagon-Like Peptide 1