<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/NCT02993614</url>
  </required_header>
  <id_info>
    <org_study_id>D1690R00015</org_study_id>
    <nct_id>NCT02993614</nct_id>
  </id_info>
  <brief_title>Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors</brief_title>
  <acronym>CVD-REAL</acronym>
  <official_title>Characteristics and Cardiovascular and Mortality Outcomes in Patients With Type 2 Diabetes Mellitus Initiating Treatment With Sodium-glucose Co-transporter-2 Inhibitors (SGLT-2i) and Other Glucose Lowering Drugs</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AstraZeneca</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      CVD-REAL is a multinational, observational cohort study in patients with type 2 diabetes&#xD;
      mellitus evaluating the comparative effectiveness of initiating treatment with a&#xD;
      sodium-glucose co-transporter-2 (SGLT-2) inhibitor versus another glucose-lowering drug. This&#xD;
      study will compare the risk of all-cause mortality and clinically relevant cardiovascular&#xD;
      (CV) outcomes respectively in patients who are new users of SGLT-2 inhibitors with those who&#xD;
      are new users of other glucose-lowering drugs. CVD-REAL is aiming to collect data from&#xD;
      approximately 4 million patients overall, from twelve countries across three major world&#xD;
      regions.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Type 2 diabetes mellitus remains a major risk factor for cardiovascular disease with an&#xD;
      estimated 425 million adults worldwide having diabetes in 2017, with type 2 diabetes mellitus&#xD;
      accounting for about 90% of the cases. Recent evidence indicates that certain&#xD;
      glucose-lowering therapies are associated with reduction in cardiovascular outcomes. There&#xD;
      is, therefore, an urgent need to improve the understanding of the impact of newer classes of&#xD;
      glucose-lowering therapies, such as dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like&#xD;
      peptide-1 (GLP-1) receptor agonists and sodium-glucose co-transporter-2 (SGLT-2) inhibitors&#xD;
      on cardiovascular outcomes in clinical practice.&#xD;
&#xD;
      CVD-REAL is a comparative effectiveness study that aims to compare new users of SGLT-2&#xD;
      inhibitors with new users of other glucose-lowering drugs with regard to the risk of&#xD;
      all-cause mortality and clinically relevant CV outcomes (including stroke, myocardial&#xD;
      infarction, and hospitalization for heart failure) respectively. The study is based on data&#xD;
      from 12 countries across four major world regions.&#xD;
&#xD;
      The study is conducted using data from claims, medical records and national health registries&#xD;
      from twelve countries combined in two waves. CVD-REAL 1 includes Germany, Denmark, Norway,&#xD;
      Sweden, United Kingdom (UK) and United States of America (USA). CVD-REAL 2 comprises&#xD;
      Australia, Canada, Israel, Japan, Singapore and South Korea. The study will collect data from&#xD;
      approximately 4 million patients from the time they start treatment with a SGLT-2 inhibitor&#xD;
      or another glucose-lowering drug (index date) to the end of the follow-up period.&#xD;
&#xD;
      The Study Population will consist of new users of SGLT-2i and other glucose lowering drugs&#xD;
      respectively. These will be compared with all-cause mortality, hospitalization for heart&#xD;
      failure, myocardial infarction and stroke during the follow-up period. In addition certain&#xD;
      other cardiovascular and renal outcomes will be assessed descriptively in the two groups&#xD;
      respectively.&#xD;
&#xD;
      The study period will range from launch of the first SGLT-2i in each of the countries and end&#xD;
      at latest available data in each data source.&#xD;
&#xD;
      All-cause mortality and the incidence of cardiovascular events will be compared between new&#xD;
      users of SGLT-2 inhibitors and the comparator arm using a hazard ratio (relative risk) and&#xD;
      corresponding 95% confidence interval. The analysis will be performed using the Cox&#xD;
      proportional hazards model or some other appropriate method.&#xD;
&#xD;
      Matching by propensity scores will be used to balance the potential confounding covariates&#xD;
      between the SGLT-2i group and the reference group to ensure that the two groups are as&#xD;
      similar as possible at baseline.To achieve sufficient power, a meta-analysis will be applied&#xD;
      to integrate the point estimates from each of the individual database analyses and calculate&#xD;
      an overall weighted estimate and corresponding 95% CI.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 30, 2017</start_date>
  <completion_date type="Actual">December 17, 2020</completion_date>
  <primary_completion_date type="Actual">December 17, 2020</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>CVD REAL1 Incidence of hospitalization for heart failure. / CVD REAL 2 All-cause mortality</measure>
    <time_frame>From index date up to latest available data of first prescription of an SGLT-2i or a new oGLD in each of the countries ranging from Sep 11 (UK) until Apr 15 (IL) until the last date of data collection or outcome ranging from Sep 15 (US) to Nov 17 (SG)</time_frame>
    <description>Heart failure events obtained from general practice or hospital records, electronic health records or national health registers; All-cause mortality obtained from linkeage to death national registers</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>CVD REAL1 All-cause mortality; CVD REAL 2: Hospitalization for heart failure (HHF), stroke, myocardial infarction (MI) and including composite endpoints</measure>
    <time_frame>From index date up to latest available data of first prescription of an SGLT-2i or a new oGLD in each of the countries ranging from Sep 11 (UK) until Apr 15 (IL) until the last date of data collection or outcome ranging from Sep 15 (US) to Nov 17 (SG)</time_frame>
    <description>Events obtained from general practice or hospital records, electronic health records and national health registers. All cause mortality obtained from linkeage to death national registers</description>
  </secondary_outcome>
  <enrollment type="Actual">99999</enrollment>
  <condition>Diabetes Mellitus Type 2</condition>
  <eligibility>
    <study_pop>
      <textblock>
        New users of SGLT--2i and other glucose lowering drugs respectively&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  New user receiving or dispensed prescription of SGLT-2i medication or other glucose&#xD;
             lowering drug, oral as well as injectable, including fixed-dose combination (FDC)&#xD;
             products containing these medication groups&#xD;
&#xD;
          -  T2DM diagnosis on or prior to the index date&#xD;
&#xD;
          -  ≥ 18 years old at index date&#xD;
&#xD;
          -  &gt; 1 year data history in the database prior to the index date&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with a T1DM diagnosis&#xD;
&#xD;
          -  Patients with gestational diabetes within 1 year before index date&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Wilmington</city>
        <state>Delaware</state>
        <zip>19850</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Melbourne</city>
        <state>D1690r00015</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Mississauga</city>
        <state>D1690r00015</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Gentofte</city>
        <state>D1690r00015</state>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Espoo</city>
        <state>D1690r00015</state>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ulm</city>
        <state>D1690r00015</state>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Raanana</city>
        <state>D1690r00015</state>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Rome</city>
        <state>D1690r00015</state>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tokyo</city>
        <state>D1690r00015</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Seoul</city>
        <state>D1690r00015</state>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Oslo</city>
        <state>D1690r00015</state>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Porto</city>
        <state>D1690r00015</state>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Singapore</city>
        <state>D1690r00015</state>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Madrid</city>
        <state>D1690r00015</state>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sodertalje</city>
        <state>D1690r00015</state>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Taipei</city>
        <state>D1690r00015</state>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Luton</city>
        <state>D1690r00015</state>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Canada</country>
    <country>Denmark</country>
    <country>Finland</country>
    <country>Germany</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Norway</country>
    <country>Portugal</country>
    <country>Singapore</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>Taiwan</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&amp;studyid=14609&amp;filename=CSP_D1690R00015.pdf</url>
    <description>CSP_D1690R00015.</description>
  </link>
  <link>
    <url>http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&amp;studyid=14609&amp;filename=CSP_amendment_D1690R00015.pdf</url>
    <description>CSP_amendment_D1690R00015.</description>
  </link>
  <link>
    <url>https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;amp;parentIdentifier=D1690R00015&amp;amp;attachmentIdentifier=8e066078-f806-4731-a5d6-607baa08816f&amp;amp;fileName=CSR_CVD-REAL_15_Dec_redacted.docx&amp;amp;versionIdentifier=</url>
    <description>Redacted CSR Synopsis</description>
  </link>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>December 13, 2016</study_first_submitted>
  <study_first_submitted_qc>December 13, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 15, 2016</study_first_posted>
  <last_update_submitted>February 17, 2021</last_update_submitted>
  <last_update_submitted_qc>February 17, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 18, 2021</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>
  <!-- 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/NCT02993614
org study id: D1690R00015
nct id: NCT02993614
lead sponsor: 
has dmc: No
CVD-REAL is a multinational, observational cohort study in patients with type 2 diabetes
      mellitus evaluating the comparative effectiveness of initiating treatment with a
      sodium-glucose co-transporter-2 (SGLT-2) inhibitor versus another glucose-lowering drug. This
      study will compare the risk of all-cause mortality and clinically relevant cardiovascular
      (CV) outcomes respectively in patients who are new users of SGLT-2 inhibitors with those who
      are new users of other glucose-lowering drugs. CVD-REAL is aiming to collect data from
      approximately 4 million patients overall, from twelve countries across three major world
      regions.
Type 2 diabetes mellitus remains a major risk factor for cardiovascular disease with an
      estimated 425 million adults worldwide having diabetes in 2017, with type 2 diabetes mellitus
      accounting for about 90% of the cases. Recent evidence indicates that certain
      glucose-lowering therapies are associated with reduction in cardiovascular outcomes. There
      is, therefore, an urgent need to improve the understanding of the impact of newer classes of
      glucose-lowering therapies, such as dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like
      peptide-1 (GLP-1) receptor agonists and sodium-glucose co-transporter-2 (SGLT-2) inhibitors
      on cardiovascular outcomes in clinical practice.

      CVD-REAL is a comparative effectiveness study that aims to compare new users of SGLT-2
      inhibitors with new users of other glucose-lowering drugs with regard to the risk of
      all-cause mortality and clinically relevant CV outcomes (including stroke, myocardial
      infarction, and hospitalization for heart failure) respectively. The study is based on data
      from 12 countries across four major world regions.

      The study is conducted using data from claims, medical records and national health registries
      from twelve countries combined in two waves. CVD-REAL 1 includes Germany, Denmark, Norway,
      Sweden, United Kingdom (UK) and United States of America (USA). CVD-REAL 2 comprises
      Australia, Canada, Israel, Japan, Singapore and South Korea. The study will collect data from
      approximately 4 million patients from the time they start treatment with a SGLT-2 inhibitor
      or another glucose-lowering drug (index date) to the end of the follow-up period.

      The Study Population will consist of new users of SGLT-2i and other glucose lowering drugs
      respectively. These will be compared with all-cause mortality, hospitalization for heart
      failure, myocardial infarction and stroke during the follow-up period. In addition certain
      other cardiovascular and renal outcomes will be assessed descriptively in the two groups
      respectively.

      The study period will range from launch of the first SGLT-2i in each of the countries and end
      at latest available data in each data source.

      All-cause mortality and the incidence of cardiovascular events will be compared between new
      users of SGLT-2 inhibitors and the comparator arm using a hazard ratio (relative risk) and
      corresponding 95% confidence interval. The analysis will be performed using the Cox
      proportional hazards model or some other appropriate method.

      Matching by propensity scores will be used to balance the potential confounding covariates
      between the SGLT-2i group and the reference group to ensure that the two groups are as
      similar as possible at baseline.To achieve sufficient power, a meta-analysis will be applied
      to integrate the point estimates from each of the individual database analyses and calculate
      an overall weighted estimate and corresponding 95% CI.
observational model: Cohort
time perspective: Prospective
measure: CVD REAL1 Incidence of hospitalization for heart failure. / CVD REAL 2 All-cause mortality
time frame: From index date up to latest available data of first prescription of an SGLT-2i or a new oGLD in each of the countries ranging from Sep 11 (UK) until Apr 15 (IL) until the last date of data collection or outcome ranging from Sep 15 (US) to Nov 17 (SG)
description: Heart failure events obtained from general practice or hospital records, electronic health records or national health registers; All-cause mortality obtained from linkeage to death national registers
measure: CVD REAL1 All-cause mortality; CVD REAL 2: Hospitalization for heart failure (HHF), stroke, myocardial infarction (MI) and including composite endpoints
time frame: From index date up to latest available data of first prescription of an SGLT-2i or a new oGLD in each of the countries ranging from Sep 11 (UK) until Apr 15 (IL) until the last date of data collection or outcome ranging from Sep 15 (US) to Nov 17 (SG)
description: Events obtained from general practice or hospital records, electronic health records and national health registers. All cause mortality obtained from linkeage to death national registers
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
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facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
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facility: 
country: Australia
country: Canada
country: Denmark
country: Finland
country: Germany
country: Israel
country: Italy
country: Japan
country: Korea, Republic of
country: Norway
country: Portugal
country: Singapore
country: Spain
country: Sweden
country: Taiwan
country: United Kingdom
country: United States
url: http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=14609&filename=CSP_D1690R00015.pdf
description: CSP_D1690R00015.
url: http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=14609&filename=CSP_amendment_D1690R00015.pdf
description: CSP_amendment_D1690R00015.
url: https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D1690R00015&amp;attachmentIdentifier=8e066078-f806-4731-a5d6-607baa08816f&amp;fileName=CSR_CVD-REAL_15_Dec_redacted.docx&amp;versionIdentifier=
description: Redacted CSR Synopsis
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2