<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/NCT04419337</url>
  </required_header>
  <id_info>
    <org_study_id>MOST 108-2314-B-182-017-</org_study_id>
    <nct_id>NCT04419337</nct_id>
  </id_info>
  <brief_title>Pioglitazone and SGLT2 Inhibitors vs. DPP4 Inhibitors in Patients With Stroke</brief_title>
  <official_title>Comparison of Combined Pioglitazone and SGLT2 Inhibitors vs. DPP4 Inhibitors in Diabetic Patients With Ischemic Stroke: Rationale and Study Design</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chang Gung Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Chiayi Christian Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Tainan Sin-lau Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Chang Gung Memorial Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Introduction: An optimal combination of antidiabetic drugs for diabetic patients with&#xD;
      ischemic stroke is not well-established. The objective of this randomized trial is to&#xD;
      evaluate whether combination of pioglitazone and a sodium glucose cotransporter 2 (SGLT-2)&#xD;
      inhibitor, compared with a dipeptidyl peptidase-4 (DPP-4) inhibitor, reduces recurrent stroke&#xD;
      in diabetic patients with recent ischemic stroke.&#xD;
&#xD;
      Methods and analysis: The trial is a randomized, parallel-group study conducted at 7&#xD;
      hospitals in Taiwan. Inclusion criteria are adult patients with a history of ischemic stroke&#xD;
      within 3 months, diabetes mellitus with Hba1C &gt; 7%, taking metformin currently or previously,&#xD;
      and estimated glomerular filtration rate ≥ 45 mL/min/1.73 m2. Eligible patients who sign the&#xD;
      informed consent forms will be randomly assigned in a 1:1 ratio to receive either combination&#xD;
      of pioglitazone and an SGLT2 inhibitor (empagliflozin or dapagliflozin or canagliflozin) vs.&#xD;
      a DPP4 inhibitor. Primary outcome is change in HbA1C between 6 months and baseline in active&#xD;
      vs comparator groups. Additional biomarker outcomes are change in hs-CRP insulin resistance,&#xD;
      B type natriuretic peptide, and urine albumin creatinine ratio between 6 months and baseline.&#xD;
&#xD;
      Ethics and dissemination Study protocol was approved by the Institutional Review Board of&#xD;
      Chang Gung Memorial Hospital, Chiayi Branch, Taiwan (201702353A3, 201802340A3 and&#xD;
      201902176A3). All participants will be required to sign and date an informed consent form.&#xD;
      Study findings will be disseminated via a peer-reviewed journal.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 15, 2019</start_date>
  <completion_date type="Anticipated">January 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">July 31, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>HbA1C</measure>
    <time_frame>6 months from baseline in active vs control arms</time_frame>
    <description>blood test to evaluate glycemic control</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>UACR</measure>
    <time_frame>6 months from randomization in active vs control arms</time_frame>
    <description>to evaluate microalbuminuria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>hs-CRP</measure>
    <time_frame>6 months from randomization</time_frame>
    <description>to evaluate hs-CRP in active vs control arms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NT-proBNP</measure>
    <time_frame>6 months from randomization</time_frame>
    <description>to evaluate NT-proBNP in active vs control arms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>insulin resistance</measure>
    <time_frame>6 months from randomization</time_frame>
    <description>Insulin resistance will be evaluated by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Diabetes Mellitus</condition>
  <condition>Stroke</condition>
  <arm_group>
    <arm_group_label>Active arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>metformin+pioglitazone+an SGLT2 inhibitor</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>metformin + DPP4 inhibitors</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin plus Pioglitazone plus an SGLT2 inhibitor</intervention_name>
    <description>Patients assigned to active group will stop their prior oral antidiabetic drugs and receive combination of metformin, pioglitazone, and an SGLT2 inhibitor (empagliflozin or dapagliflozin or canagliflozin) and dose will be adjusted by their physicians.</description>
    <arm_group_label>Active arm</arm_group_label>
    <arm_group_label>Control arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Ischemic stroke within 3 months of randomization&#xD;
&#xD;
          2. Type 2 diabetes mellitus and Hba1C &gt; 7.0% and under metformin therapy currently or&#xD;
             previously&#xD;
&#xD;
          3. Estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m2&#xD;
&#xD;
          4. Age ≥ 20 y at study entry&#xD;
&#xD;
          5. Ability and willingness to provide informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of congestive heart failure (NYHA class 1-4)&#xD;
&#xD;
          2. History of bladder cancer&#xD;
&#xD;
          3. History of repeated (&gt; 2 episodes) urinary tract infection or genital tract infection&#xD;
&#xD;
          4. Irreversible medical conditions with predicted survival &lt; 1 years&#xD;
&#xD;
          5. Current use of an insulin&#xD;
&#xD;
          6. Current use of a glucagon-like peptide-1 receptor agonist&#xD;
&#xD;
          7. Current use of pioglitazone or an SGLT-2 inhibitor&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Meng Lee, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chang Gung Memorial Hospital, Chiayi Branch</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Meng Lee, MD</last_name>
    <phone>8863621000</phone>
    <phone_ext>2806</phone_ext>
    <email>menlee5126@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Chang Gung Memorial Hospital, Chiayi Branch</name>
      <address>
        <city>Chiayi City</city>
        <zip>613</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Meng Lee, MD</last_name>
      <phone>88653621000</phone>
      <phone_ext>2806</phone_ext>
      <email>menglee5126@gmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>February 26, 2020</study_first_submitted>
  <study_first_submitted_qc>June 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 5, 2020</study_first_posted>
  <last_update_submitted>March 28, 2023</last_update_submitted>
  <last_update_submitted_qc>March 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 30, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>stroke</keyword>
  <keyword>diabetes mellitus</keyword>
  <keyword>sodium-glucose transport protein 2 inhibitor</keyword>
  <keyword>pioglitazone</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
    <mesh_term>Diabetes Mellitus</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
    <mesh_term>Pioglitazone</mesh_term>
    <mesh_term>Sodium-Glucose Transporter 2 Inhibitors</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/NCT04419337
org study id: MOST 108-2314-B-182-017-
nct id: NCT04419337
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Introduction: An optimal combination of antidiabetic drugs for diabetic patients with
      ischemic stroke is not well-established. The objective of this randomized trial is to
      evaluate whether combination of pioglitazone and a sodium glucose cotransporter 2 (SGLT-2)
      inhibitor, compared with a dipeptidyl peptidase-4 (DPP-4) inhibitor, reduces recurrent stroke
      in diabetic patients with recent ischemic stroke.

      Methods and analysis: The trial is a randomized, parallel-group study conducted at 7
      hospitals in Taiwan. Inclusion criteria are adult patients with a history of ischemic stroke
      within 3 months, diabetes mellitus with Hba1C > 7%, taking metformin currently or previously,
      and estimated glomerular filtration rate ≥ 45 mL/min/1.73 m2. Eligible patients who sign the
      informed consent forms will be randomly assigned in a 1:1 ratio to receive either combination
      of pioglitazone and an SGLT2 inhibitor (empagliflozin or dapagliflozin or canagliflozin) vs.
      a DPP4 inhibitor. Primary outcome is change in HbA1C between 6 months and baseline in active
      vs comparator groups. Additional biomarker outcomes are change in hs-CRP insulin resistance,
      B type natriuretic peptide, and urine albumin creatinine ratio between 6 months and baseline.

      Ethics and dissemination Study protocol was approved by the Institutional Review Board of
      Chang Gung Memorial Hospital, Chiayi Branch, Taiwan (201702353A3, 201802340A3 and
      201902176A3). All participants will be required to sign and date an informed consent form.
      Study findings will be disseminated via a peer-reviewed journal.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: HbA1C
time frame: 6 months from baseline in active vs control arms
description: blood test to evaluate glycemic control
measure: UACR
time frame: 6 months from randomization in active vs control arms
description: to evaluate microalbuminuria
measure: hs-CRP
time frame: 6 months from randomization
description: to evaluate hs-CRP in active vs control arms
measure: NT-proBNP
time frame: 6 months from randomization
description: to evaluate NT-proBNP in active vs control arms
measure: insulin resistance
time frame: 6 months from randomization
description: Insulin resistance will be evaluated by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)
arm group label: Active arm
arm group type: Experimental
description: metformin+pioglitazone+an SGLT2 inhibitor
arm group label: Control arm
arm group type: Active Comparator
description: metformin + DPP4 inhibitors
intervention type: Drug
intervention name: Metformin plus Pioglitazone plus an SGLT2 inhibitor
description: Patients assigned to active group will stop their prior oral antidiabetic drugs and receive combination of metformin, pioglitazone, and an SGLT2 inhibitor (empagliflozin or dapagliflozin or canagliflozin) and dose will be adjusted by their physicians.
arm group label: Active arm
arm group label: Control arm
criteria: 
gender: All
minimum age: 20 Years
maximum age: 99 Years
healthy volunteers: No
last name: Meng Lee, MD
role: Principal Investigator
affiliation: Chang Gung Memorial Hospital, Chiayi Branch
last name: Meng Lee, MD
phone: 8863621000
phone ext: 2806
email: menlee5126@gmail.com
facility: 
status: Recruiting
contact: 
country: Taiwan
responsible party type: Sponsor
mesh term: Stroke
mesh term: Diabetes Mellitus
mesh term: Metformin
mesh term: Pioglitazone
mesh term: Sodium-Glucose Transporter 2 Inhibitors
sharing ipd: No