<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/NCT01731431</url>
  </required_header>
  <id_info>
    <org_study_id>P110104</org_study_id>
    <nct_id>NCT01731431</nct_id>
  </id_info>
  <brief_title>Multicenter Randomized Trial of Non-inferiority Between Glyburide and Insulin for the Treatment of Gestational Diabetes</brief_title>
  <acronym>INDAO</acronym>
  <official_title>Multicenter Randomized Trial of Non-inferiority Between Glyburide and Insulin for the Treatment of Gestational Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This clinical trial aims to test whether glibenclamide is non-inferior to insulin for the&#xD;
      treatment of gestational diabetes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In patients with gestational diabetes, a therapeutic treatment with a diet, a blood glucose&#xD;
      monitoring and, if necessary, treatment with insulin is associated with reduced neonatal&#xD;
      complications. Although the effectiveness of insulin is proven, this therapy has many&#xD;
      drawbacks, especially in terms of implementation and monitoring by women. An alternative is&#xD;
      the use of oral antidiabetic agents like glibenclamide.&#xD;
&#xD;
      Assumption: Glibenclamide is non-inferior to insulin for the treatment of gestational&#xD;
      diabetes.&#xD;
&#xD;
      Main objective: To test the oral Glibenclamide is non-inferior to subcutaneous insulin for&#xD;
      the occurrence of perinatal complications in the management of pregnant women developing&#xD;
      gestational diabetes and requiring treatment other than dietary.&#xD;
&#xD;
      Secondary Objective: To test the noninferiority of two treatments on maternal glycemic&#xD;
      control and maternal complications.&#xD;
&#xD;
      Sample size: With a 80% power and a significance level of 5%, 450 subjects per group are&#xD;
      required to show that treatment with glibenclamide is not considered inferior to treatment&#xD;
      with insulin if the frequency of outcome composite does not exceed 25% with glibenclamide,&#xD;
      whereas it was 18% with insulin (calculated with a non-inferiority margin of 7% and&#xD;
      considering that 20% of patients treated with glyburide and Insulin for change half of the&#xD;
      patients accept randomization).&#xD;
&#xD;
      Progress of the study: Inclusion of women between 24 and 34 weeks. Randomization between&#xD;
      Insulin and Glibenclamide after failure of 10 days of dietary treatment well done. Failure&#xD;
      defined by at least 2 abnormal values of glycemia: fasting glucose ≥ 0.95 g / l and/or a&#xD;
      postprandial 2h ≥ 1.20 g / l.&#xD;
&#xD;
      Women will receive either insulin according to the usual protocol or Glibenclamide at an&#xD;
      initial dose of 2.5 mg / once daily in the morning before breakfast. So long as the glycemic&#xD;
      targets will not be reached doses are gradually increased stepwise every 4 days until day 21&#xD;
      (20mg/j) . Patients who have not reached the glycemic targets at this highest dose will have&#xD;
      a change in treatment for insulin at day 21. Routine monitoring of pregnant women with&#xD;
      gestational diabetes, up to a week after delivery Number of clinical sites: 15 Perspective:&#xD;
      Use of Glibenclamide as a first line treatment of gestational diabetes requiring drug&#xD;
      treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 18, 2012</start_date>
  <completion_date type="Actual">June 2, 2017</completion_date>
  <primary_completion_date type="Actual">March 15, 2017</primary_completion_date>
  <phase>Phase 3</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>Composite criterion of neonatal complications associated with gestational diabetes: macrosomia or birth weight ≥ 90th percentile for gestational age, neonatal hypoglycemia and neonatal hyperbilirubinemia</measure>
    <time_frame>At birth until neonatal discharge from maternity</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rates of caesarean section, preterm delivery rate, neonatal mortality rate, number of neonatal and maternal trauma related to delivery, number of respiratory distress, number of prenatal visits, number of days of hospitalization</measure>
    <time_frame>during pregnancy until maternal discharge from maternity</time_frame>
    <description>Maternal glycemic control, rates of caesarean section, preterm delivery rate, neonatal mortality rate, number of neonatal and maternal trauma related to delivery, number of respiratory distress, number of prenatal visits, number of days of hospitalization and maternal satisfaction</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">914</enrollment>
  <condition>Diabetes</condition>
  <condition>Gestational</condition>
  <arm_group>
    <arm_group_label>Insulin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>standard protocol of insulin treatment for gestational diabetes</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Glyburide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>initial dose 2.5 mg per day increased if necessary until 10mg twice a day if glycemia is not controlled</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Insulin</intervention_name>
    <arm_group_label>Insulin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Glyburide</intervention_name>
    <arm_group_label>Glyburide</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  gestational diabetes diagnosed between 24 and 34 weeks according to international&#xD;
             criteria.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Multiple Pregnancy&#xD;
&#xD;
          -  Chronic Hypertension&#xD;
&#xD;
          -  Preeclampsia&#xD;
&#xD;
          -  Renal impairment&#xD;
&#xD;
          -  Hepatic insufficiency&#xD;
&#xD;
          -  Long time corticosteroids treatment&#xD;
&#xD;
          -  Allergy to sulfa drugs&#xD;
&#xD;
          -  Pre-existing diabetes in pregnancy&#xD;
&#xD;
          -  Abnormal result on screening test for gestational diabetes before 24SA&#xD;
&#xD;
          -  Fasting glucose ≥ 1.26 g / l at initial diagnosis of diabetes&#xD;
&#xD;
          -  The need for drug treatment contraindicated or not recommended with taking&#xD;
             Glibenclamide&#xD;
&#xD;
          -  Poor understanding of French&#xD;
&#xD;
          -  Lack of Social Insurance&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marie-Victoire SENAT, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Marie-Victoire Senat</name>
      <address>
        <city>Paris</city>
        <zip>94270</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>December 2017</verification_date>
  <study_first_submitted>September 11, 2012</study_first_submitted>
  <study_first_submitted_qc>November 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2012</study_first_posted>
  <last_update_submitted>December 7, 2017</last_update_submitted>
  <last_update_submitted_qc>December 7, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">December 8, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Gestational Diabetes,</keyword>
  <keyword>Insulin,</keyword>
  <keyword>Glyburide,</keyword>
  <keyword>Glycemia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes, Gestational</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>Glyburide</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/NCT01731431
org study id: P110104
nct id: NCT01731431
lead sponsor: 
has dmc: Yes
This clinical trial aims to test whether glibenclamide is non-inferior to insulin for the
      treatment of gestational diabetes.
In patients with gestational diabetes, a therapeutic treatment with a diet, a blood glucose
      monitoring and, if necessary, treatment with insulin is associated with reduced neonatal
      complications. Although the effectiveness of insulin is proven, this therapy has many
      drawbacks, especially in terms of implementation and monitoring by women. An alternative is
      the use of oral antidiabetic agents like glibenclamide.

      Assumption: Glibenclamide is non-inferior to insulin for the treatment of gestational
      diabetes.

      Main objective: To test the oral Glibenclamide is non-inferior to subcutaneous insulin for
      the occurrence of perinatal complications in the management of pregnant women developing
      gestational diabetes and requiring treatment other than dietary.

      Secondary Objective: To test the noninferiority of two treatments on maternal glycemic
      control and maternal complications.

      Sample size: With a 80% power and a significance level of 5%, 450 subjects per group are
      required to show that treatment with glibenclamide is not considered inferior to treatment
      with insulin if the frequency of outcome composite does not exceed 25% with glibenclamide,
      whereas it was 18% with insulin (calculated with a non-inferiority margin of 7% and
      considering that 20% of patients treated with glyburide and Insulin for change half of the
      patients accept randomization).

      Progress of the study: Inclusion of women between 24 and 34 weeks. Randomization between
      Insulin and Glibenclamide after failure of 10 days of dietary treatment well done. Failure
      defined by at least 2 abnormal values of glycemia: fasting glucose ≥ 0.95 g / l and/or a
      postprandial 2h ≥ 1.20 g / l.

      Women will receive either insulin according to the usual protocol or Glibenclamide at an
      initial dose of 2.5 mg / once daily in the morning before breakfast. So long as the glycemic
      targets will not be reached doses are gradually increased stepwise every 4 days until day 21
      (20mg/j) . Patients who have not reached the glycemic targets at this highest dose will have
      a change in treatment for insulin at day 21. Routine monitoring of pregnant women with
      gestational diabetes, up to a week after delivery Number of clinical sites: 15 Perspective:
      Use of Glibenclamide as a first line treatment of gestational diabetes requiring drug
      treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Composite criterion of neonatal complications associated with gestational diabetes: macrosomia or birth weight ≥ 90th percentile for gestational age, neonatal hypoglycemia and neonatal hyperbilirubinemia
time frame: At birth until neonatal discharge from maternity
measure: Rates of caesarean section, preterm delivery rate, neonatal mortality rate, number of neonatal and maternal trauma related to delivery, number of respiratory distress, number of prenatal visits, number of days of hospitalization
time frame: during pregnancy until maternal discharge from maternity
description: Maternal glycemic control, rates of caesarean section, preterm delivery rate, neonatal mortality rate, number of neonatal and maternal trauma related to delivery, number of respiratory distress, number of prenatal visits, number of days of hospitalization and maternal satisfaction
arm group label: Insulin
arm group type: Active Comparator
description: standard protocol of insulin treatment for gestational diabetes
arm group label: Glyburide
arm group type: Experimental
description: initial dose 2.5 mg per day increased if necessary until 10mg twice a day if glycemia is not controlled
intervention type: Other
intervention name: Insulin
arm group label: Insulin
intervention type: Drug
intervention name: Glyburide
arm group label: Glyburide
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: No
last name: Marie-Victoire SENAT, PhD
role: Principal Investigator
affiliation: Assistance Publique - Hôpitaux de Paris
facility: 
country: France
responsible party type: Sponsor
mesh term: Diabetes, Gestational
mesh term: Diabetes Mellitus
mesh term: Glyburide