<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/NCT02253121</url>
  </required_header>
  <id_info>
    <org_study_id>NL49690.048.14</org_study_id>
    <secondary_id>2014-001877-15</secondary_id>
    <nct_id>NCT02253121</nct_id>
  </id_info>
  <brief_title>Glucose Control During Glucocorticoid Therapy in Acute Exacerbation of Chronic Obstructive Pulmonary Disease</brief_title>
  <acronym>GluCon-COPD</acronym>
  <official_title>Randomized, Double-blind, Placebo-controlled Trial on the Effectiveness and Safety of Dapagliflozin for Blood Glucose Control During Glucocorticoid Treatment for Acute Exacerbation COPD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Slotervaart Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Isala</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Spaarne Gasthuis</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Slotervaart Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Purpose of this study is to treat glucocorticoid induced hyperglycemia due to glucocorticoid&#xD;
      pulse therapy in a efficacious, safe and convenient way. Patients with acute exacerbation of&#xD;
      COPD treated with glucocorticoid pulse therapy and at high risk for glucocorticoid induced&#xD;
      hyperglycemia (defined as known type 2 DM or glucose &gt; 10mmol/l at admission) will be&#xD;
      randomized to treatment of dapagliflozin or placebo orally, once daily.&#xD;
&#xD;
      Percentage of time within glucose target range (3,9-10 mmol/l) and incidence rate of&#xD;
      hypoglycemia will be compared between dapagliflozin group and placebo group.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Rationale: Patients hospitalized for COPD exacerbation treated with high dose&#xD;
      glucocorticoids, frequently develop hyperglycaemia. Currently, sliding scale insulin is often&#xD;
      used to bridge such episodes. However, sliding scale insulin is patient unfriendly, does not&#xD;
      reduce glycaemic excursion nor glycaemic variability. In contrast, pharmacologic inhibition&#xD;
      of the sodium glucose transporter-2 (SGLT-2) can be given as an oral agent and is likely to&#xD;
      result in better glucose control with lower risk of hypoglycaemia Objective: glucose control&#xD;
      and safety (risk of hypoglycaemia). Secondary objectives are patient satisfaction, other&#xD;
      safety outcomes and other parameters of glucose control Study design: Double-blind placebo&#xD;
      controlled intervention study Study population: Patients hospitalized for an exacerbation of&#xD;
      chronic obstructive lung disease who are treated with high dose glucocorticoids.&#xD;
&#xD;
      Intervention: One group receives once daily a 10mg tablet of dapagliflozin and the other&#xD;
      group receives once daily a placebo tablet as add on to their prestudy glucose-lowering&#xD;
      medication. Both groups will be treated with glucose lowering escape medication if required.&#xD;
&#xD;
      Main study parameters/endpoints: Glucose control is measured as the average time spent within&#xD;
      target range in each patient. Safety is measured as the incidence rate of hypoglycaemia&#xD;
      during study follow-up.&#xD;
&#xD;
      Nature and extent of the burden and risks associated with participation, benefit and group&#xD;
      relatedness: The burden of participation consists of the extra capillary glucose measurements&#xD;
      that will be done 3-4 times daily and wearing a coin size glucose sensor. Furthermore,&#xD;
      patients have to fill out a treatment satisfaction questionnaire. There will be no extra site&#xD;
      visits for participants.&#xD;
&#xD;
      Dapagliflozin (experimental group) carries a risk of hypoglycaemia, especially for patient&#xD;
      who have concomitant therapy with insulin or sulfonylurea derivatives. Patients will be&#xD;
      instructed to anticipate, and if required dosing of glucose lowering therapy will be&#xD;
      adjusted. Furthermore, dapagliflozin carries an increased risk of urogenital infections,&#xD;
      increased haematocrit and LDL cholesterol.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 2015</start_date>
  <completion_date type="Actual">May 2017</completion_date>
  <primary_completion_date type="Actual">March 2016</primary_completion_date>
  <phase>Phase 4</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Glucose control</measure>
    <time_frame>2nd till 7th day of treatment</time_frame>
    <description>% time within target range (3.9-10 mmol/l)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Risk of hypoglycemia</measure>
    <time_frame>Randomisation till end of study (expected duration of 12 days)</time_frame>
    <description>Incidence rate of hypoglycaemic events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Patient satisfaction</measure>
    <time_frame>During hospital stay (expected average of 9 days)</time_frame>
    <description>Diabetes treatment satisfaction questionnaire for inpatients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical outcomes</measure>
    <time_frame>During hospital stay (expected average of 9 days)</time_frame>
    <description>Duration of hospitalisation, need for treatment escalation, incidence (re-)infections, change in body weight and blood pressure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety</measure>
    <time_frame>Randomisation till end of study (expected duration of 12 days)</time_frame>
    <description>incidence rate of asymptomatic hypoglycaemia, incidence adverse events of special interest (genital infections, urinary tract infections, renal impairment, liver injury and breast-, bladder- and prostate cancer), incidence of other adverse events.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">46</enrollment>
  <condition>Hyperglycemia Steroid-induced</condition>
  <arm_group>
    <arm_group_label>Dapagliflozin + sliding scale insulin.</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment with dapagliflozin 10mg once daily orally. Treatment will start as soon as possible after initation of glucocorticoid pulse therapy for acute exacerbation COPD and will end when pulse therapy is finished (expected duration 10-14 days). In case of persistent glucose levels &gt; 12 mmol/l, subjects will receive escape treatment with sliding scale insulin.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo + sliding scale insulin</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Treatment with placebo once daily orally. Treatment will start as soon as possible after initation of glucocorticoid pulse therapy for acute exacerbation COPD and will end when pulse therapy is finished (expected duration 10-14 days). In case of persistent glucose levels &gt; 12 mmol/l, subjects will receive escape treatment with sliding scale insulin.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dapagliflozin</intervention_name>
    <description>Dapagliflozin 10mg during glucocorticoid therapy for acute exacerbation COPD</description>
    <arm_group_label>Dapagliflozin + sliding scale insulin.</arm_group_label>
    <other_name>Forxiga</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sliding scale insulin</intervention_name>
    <description>Sliding scale insulin with short acting insulin based on current glucose levels</description>
    <arm_group_label>Dapagliflozin + sliding scale insulin.</arm_group_label>
    <arm_group_label>Placebo + sliding scale insulin</arm_group_label>
    <other_name>Supplemental insulin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Informed consent&#xD;
&#xD;
          -  Hospitalization due to AECOPD&#xD;
&#xD;
          -  Treatment with ≥30mg prednisone daily or equivalent dose of glucocorticoid for AECOPD&#xD;
&#xD;
          -  An expected duration of glucocorticoid treatment of 3-14 days at study entry&#xD;
&#xD;
          -  Known type 2 diabetes or glucose ≥ 10 mmol/l at admission&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  High dose glucocorticoid treatment started ≥7 days before study entry&#xD;
&#xD;
          -  Need for ICU admission&#xD;
&#xD;
          -  Chronic kidney disease stage G3 (glomerular filtration rate &lt;60ml/minute)&#xD;
&#xD;
          -  Recurrent genital or urinary tract infection&#xD;
&#xD;
          -  Current use of any SGLT-2 inhibiting agent&#xD;
&#xD;
          -  Suspected volume depletion&#xD;
&#xD;
          -  Congestive heart failure functional classification NYHA class IV/IV or instable heart&#xD;
             failure&#xD;
&#xD;
          -  Acute stroke within 2 months before inclusion.&#xD;
&#xD;
          -  Recent cardiovascular event: acute coronary syndrome, hospitalisation for unstable&#xD;
             angina or coronary revascularisation within 2 months before inclusion&#xD;
&#xD;
          -  Suspected liver disease, confirmed by AST/ALT &gt; 3x ULN or bilirubin &gt;2.0mg/dl (34.2&#xD;
             μmol/l) or serologically proven infection with hepatitis B or hepatitis C&#xD;
&#xD;
          -  Pregnancy or breast feeding&#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>Victor Gerdes, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Slotervaart Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Slotervaart Hospital</name>
      <address>
        <city>Amsterdam</city>
        <zip>1066 EC</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OLVG West</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spaarne Ziekenhuis</name>
      <address>
        <city>Hoofddorp</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Isala</name>
      <address>
        <city>Zwolle</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5947126/</url>
    <description>Related Info</description>
  </link>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>September 22, 2014</study_first_submitted>
  <study_first_submitted_qc>September 26, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 1, 2014</study_first_posted>
  <last_update_submitted>May 19, 2018</last_update_submitted>
  <last_update_submitted_qc>May 19, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 22, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COPD</keyword>
  <keyword>acute exacerbation</keyword>
  <keyword>glucocorticoid therapy</keyword>
  <keyword>hyperglycemia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperglycemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin</mesh_term>
    <mesh_term>Insulin, Globin Zinc</mesh_term>
    <mesh_term>Dapagliflozin</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/NCT02253121
org study id: NL49690.048.14
secondary id: 2014-001877-15
nct id: NCT02253121
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
Purpose of this study is to treat glucocorticoid induced hyperglycemia due to glucocorticoid
      pulse therapy in a efficacious, safe and convenient way. Patients with acute exacerbation of
      COPD treated with glucocorticoid pulse therapy and at high risk for glucocorticoid induced
      hyperglycemia (defined as known type 2 DM or glucose > 10mmol/l at admission) will be
      randomized to treatment of dapagliflozin or placebo orally, once daily.

      Percentage of time within glucose target range (3,9-10 mmol/l) and incidence rate of
      hypoglycemia will be compared between dapagliflozin group and placebo group.
Rationale: Patients hospitalized for COPD exacerbation treated with high dose
      glucocorticoids, frequently develop hyperglycaemia. Currently, sliding scale insulin is often
      used to bridge such episodes. However, sliding scale insulin is patient unfriendly, does not
      reduce glycaemic excursion nor glycaemic variability. In contrast, pharmacologic inhibition
      of the sodium glucose transporter-2 (SGLT-2) can be given as an oral agent and is likely to
      result in better glucose control with lower risk of hypoglycaemia Objective: glucose control
      and safety (risk of hypoglycaemia). Secondary objectives are patient satisfaction, other
      safety outcomes and other parameters of glucose control Study design: Double-blind placebo
      controlled intervention study Study population: Patients hospitalized for an exacerbation of
      chronic obstructive lung disease who are treated with high dose glucocorticoids.

      Intervention: One group receives once daily a 10mg tablet of dapagliflozin and the other
      group receives once daily a placebo tablet as add on to their prestudy glucose-lowering
      medication. Both groups will be treated with glucose lowering escape medication if required.

      Main study parameters/endpoints: Glucose control is measured as the average time spent within
      target range in each patient. Safety is measured as the incidence rate of hypoglycaemia
      during study follow-up.

      Nature and extent of the burden and risks associated with participation, benefit and group
      relatedness: The burden of participation consists of the extra capillary glucose measurements
      that will be done 3-4 times daily and wearing a coin size glucose sensor. Furthermore,
      patients have to fill out a treatment satisfaction questionnaire. There will be no extra site
      visits for participants.

      Dapagliflozin (experimental group) carries a risk of hypoglycaemia, especially for patient
      who have concomitant therapy with insulin or sulfonylurea derivatives. Patients will be
      instructed to anticipate, and if required dosing of glucose lowering therapy will be
      adjusted. Furthermore, dapagliflozin carries an increased risk of urogenital infections,
      increased haematocrit and LDL cholesterol.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Glucose control
time frame: 2nd till 7th day of treatment
description: % time within target range (3.9-10 mmol/l)
measure: Risk of hypoglycemia
time frame: Randomisation till end of study (expected duration of 12 days)
description: Incidence rate of hypoglycaemic events
measure: Patient satisfaction
time frame: During hospital stay (expected average of 9 days)
description: Diabetes treatment satisfaction questionnaire for inpatients
measure: Clinical outcomes
time frame: During hospital stay (expected average of 9 days)
description: Duration of hospitalisation, need for treatment escalation, incidence (re-)infections, change in body weight and blood pressure.
measure: Safety
time frame: Randomisation till end of study (expected duration of 12 days)
description: incidence rate of asymptomatic hypoglycaemia, incidence adverse events of special interest (genital infections, urinary tract infections, renal impairment, liver injury and breast-, bladder- and prostate cancer), incidence of other adverse events.
arm group label: Dapagliflozin + sliding scale insulin.
arm group type: Experimental
description: Treatment with dapagliflozin 10mg once daily orally. Treatment will start as soon as possible after initation of glucocorticoid pulse therapy for acute exacerbation COPD and will end when pulse therapy is finished (expected duration 10-14 days). In case of persistent glucose levels > 12 mmol/l, subjects will receive escape treatment with sliding scale insulin.
arm group label: Placebo + sliding scale insulin
arm group type: Placebo Comparator
description: Treatment with placebo once daily orally. Treatment will start as soon as possible after initation of glucocorticoid pulse therapy for acute exacerbation COPD and will end when pulse therapy is finished (expected duration 10-14 days). In case of persistent glucose levels > 12 mmol/l, subjects will receive escape treatment with sliding scale insulin.
intervention type: Drug
intervention name: Dapagliflozin
description: Dapagliflozin 10mg during glucocorticoid therapy for acute exacerbation COPD
arm group label: Dapagliflozin + sliding scale insulin.
other name: Forxiga
intervention type: Drug
intervention name: Sliding scale insulin
description: Sliding scale insulin with short acting insulin based on current glucose levels
arm group label: Dapagliflozin + sliding scale insulin.
arm group label: Placebo + sliding scale insulin
other name: Supplemental insulin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Victor Gerdes, MD, PhD
role: Principal Investigator
affiliation: Slotervaart Hospital
facility: 
facility: 
facility: 
facility: 
country: Netherlands
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5947126/
description: Related Info
responsible party type: Sponsor
mesh term: Hyperglycemia
mesh term: Insulin
mesh term: Insulin, Globin Zinc
mesh term: Dapagliflozin