<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/NCT02989519</url>
  </required_header>
  <id_info>
    <org_study_id>SPS2016-01</org_study_id>
    <nct_id>NCT02989519</nct_id>
  </id_info>
  <brief_title>Efficacy of Oral Progesterone and Vaginal Progesterone After Tocolytic Therapy in Threatened Preterm Labor</brief_title>
  <official_title>Comparison of the Efficacy of Oral Progesterone and Vaginal Progesterone After Tocolytic Therapy in Threatened Preterm Labor</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sanpasitthiprasong Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sanpasitthiprasong 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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine efficacy of vaginal and oral progesterone after&#xD;
      tocolytic therapy in threatened preterm labor&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A randomized controlled trial was conducted from August 2015 through December 2016. All&#xD;
      pregnant women with single pregnancies of 28 to 33 weeks and 6 days who had been experienced&#xD;
      for threatened or preterm labor with intact membrane as in inclusion criteria were approached&#xD;
      and ask for enrollment. The gestational age of all patients was confirmed by antenatal record&#xD;
      review and ultrasonographic confirmation. Threatened preterm labor was defined as the&#xD;
      presence of regular uterine contractions without significant cervical changes as determined&#xD;
      by digital pelvic examination. Preterm labor was defined as the simultaneous presence of&#xD;
      regular uterine contractions and cervical changes, shortening and/or softening, or&#xD;
      dilatation, as determined by digital pelvic examination. The women with preterm labor&#xD;
      underwent standard tocolysis, which was administered for at least 48 hours, to allow&#xD;
      corticosteroid promote fetal lung maturation. The patients who had proven membranes ruptured,&#xD;
      and ultrasonographically found placenta previa, multiple pregnancy, fetal anomaly or&#xD;
      aneuploidy would excluded. The participants had emergency condition that required for&#xD;
      emergency delivery such as fetal distress, chorioamnionitis were also excluded. Participants&#xD;
      were randomized into three groups which generated by computer programme to receive whether&#xD;
      oral progesterone (dydrogesterone 10 mg; Duphaston™) per oral three times a day or vaginal&#xD;
      progesterone (micronized progesterone 200 mg; Utrogestan™) or no progesterone (controlled&#xD;
      group). All patients were digitally pelvic examined for evaluation of Bishop score and&#xD;
      assessed cervical length by transvaginal ultrasound at enrollment and follow up visit at two&#xD;
      weeks apart. Cervical length was measured by standard technique with a covered probe inserted&#xD;
      into vagina after each woman had emptied her bladder. Excessive pressure on cervix was&#xD;
      avoided. The mean value of 3 consecutive measurements was used for analysis. Informed consent&#xD;
      and demographic data were obtained at the enrollment. Primary outcomes were preterm delivery&#xD;
      before 34 and 37 weeks. Secondary outcomes include time until delivery (latency period,days),&#xD;
      change of cervical length (cervical attenuation), maternal outcome, neonatal outcome, and&#xD;
      side effects of drugs were collected. The main outcomes of preterm delivery, gestational age&#xD;
      at parturition and birthweight were also collected by telephone call in case of&#xD;
      out-side-hospital born or in case loss to follow up. Monitoring of all patients was evaluated&#xD;
      every follow up visit for drug side effect, allergic response, and adverse events Statistical&#xD;
      analysis Sample size was calculated according to the results of two studies by Dorota&#xD;
      AgataBomba - Opon and Manju Choudhary which showed significant decreased preterm delivery &lt;34&#xD;
      weeks (9.8% vs 35.3%,p=0.002) in vaginal progesterone group, and significant decreased&#xD;
      preterm birth (33% vs 58% ; p= 0.034) in oral progesterone group. The sample size of 231 was&#xD;
      used to evaluate the primary outcome of both drugs. Descriptive statistics were carried out&#xD;
      using mean, median, standard deviation, interquartile range. Categorical data were tested for&#xD;
      significance with the χ2tests. Continuous data were evaluated for normal distribution and&#xD;
      tested for significance with ANOVA and Kruskal-Wallis test. Student t test and Man-Whitney U&#xD;
      test were used to test significance between groups in case there is significant detection in&#xD;
      ANOVA and Kruskal-Wallis test among groups. Statistical significance was defined as p&lt;0.05.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 2015</start_date>
  <completion_date type="Actual">March 1, 2017</completion_date>
  <primary_completion_date type="Actual">January 5, 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>Prevention</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>preterm delivery before 34 and 37 weeks</measure>
    <time_frame>3 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>change of cervical length</measure>
    <time_frame>2 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">231</enrollment>
  <condition>Preterm Delivery</condition>
  <arm_group>
    <arm_group_label>no progesterone</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>All women with preterm labor underwent standard tocolysis, which was administered for at least 48 hours, to allow corticosteroid promote fetal lung maturation</description>
  </arm_group>
  <arm_group>
    <arm_group_label>oral progesterone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All women with preterm labor underwent standard tocolysis, which was administered for at least 48 hours, to allow corticosteroid promote fetal lung maturation. All women in this arm received oral progesterone (dydrogesterone 10 mg; Duphaston™) per oral three times a day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>vaginal progesterone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All women with preterm labor underwent standard tocolysis, which was administered for at least 48 hours, to allow corticosteroid promote fetal lung maturation. All women in this arm received vaginal progesterone (micronized progesterone 200 mg; Utrogestan™) at bed time.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>dydrogesterone</intervention_name>
    <arm_group_label>oral progesterone</arm_group_label>
    <other_name>Duphaston</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Micronized progesterone</intervention_name>
    <arm_group_label>vaginal progesterone</arm_group_label>
    <other_name>Utrogestan</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Single pregnancies of 28 to 33 weeks and 6 days who had been experienced for&#xD;
             threatened or preterm labor with intact membrane&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Proven membranes ruptured&#xD;
&#xD;
          -  Ultrasonographically found placenta previa, multiple pregnancy, fetal anomaly&#xD;
&#xD;
          -  Aneuploidy detected.&#xD;
&#xD;
          -  Had emergency condition that required for emergency delivery such as fetal distress,&#xD;
             chorioamnionitis, prolapsed cord&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Piyawadee Wuttikonsammakit, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Instructor</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Piyawadee Wuttikonsammakit</name>
      <address>
        <city>Nai Muang</city>
        <state>Ubon Ratchathani</state>
        <zip>34000</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Thailand</country>
  </location_countries>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>December 7, 2016</study_first_submitted>
  <study_first_submitted_qc>December 9, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 12, 2016</study_first_posted>
  <last_update_submitted>October 7, 2017</last_update_submitted>
  <last_update_submitted_qc>October 7, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 10, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sanpasitthiprasong Hospital</investigator_affiliation>
    <investigator_full_name>Piyawadee Wuttikonsammakit</investigator_full_name>
    <investigator_title>Instructor</investigator_title>
  </responsible_party>
  <keyword>preterm labor</keyword>
  <keyword>progesterone efficacy</keyword>
  <keyword>threatened preterm labor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Premature Birth</mesh_term>
    <mesh_term>Obstetric Labor, Premature</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Progesterone</mesh_term>
    <mesh_term>Dydrogesterone</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/NCT02989519
org study id: SPS2016-01
nct id: NCT02989519
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to determine efficacy of vaginal and oral progesterone after
      tocolytic therapy in threatened preterm labor
A randomized controlled trial was conducted from August 2015 through December 2016. All
      pregnant women with single pregnancies of 28 to 33 weeks and 6 days who had been experienced
      for threatened or preterm labor with intact membrane as in inclusion criteria were approached
      and ask for enrollment. The gestational age of all patients was confirmed by antenatal record
      review and ultrasonographic confirmation. Threatened preterm labor was defined as the
      presence of regular uterine contractions without significant cervical changes as determined
      by digital pelvic examination. Preterm labor was defined as the simultaneous presence of
      regular uterine contractions and cervical changes, shortening and/or softening, or
      dilatation, as determined by digital pelvic examination. The women with preterm labor
      underwent standard tocolysis, which was administered for at least 48 hours, to allow
      corticosteroid promote fetal lung maturation. The patients who had proven membranes ruptured,
      and ultrasonographically found placenta previa, multiple pregnancy, fetal anomaly or
      aneuploidy would excluded. The participants had emergency condition that required for
      emergency delivery such as fetal distress, chorioamnionitis were also excluded. Participants
      were randomized into three groups which generated by computer programme to receive whether
      oral progesterone (dydrogesterone 10 mg; Duphaston™) per oral three times a day or vaginal
      progesterone (micronized progesterone 200 mg; Utrogestan™) or no progesterone (controlled
      group). All patients were digitally pelvic examined for evaluation of Bishop score and
      assessed cervical length by transvaginal ultrasound at enrollment and follow up visit at two
      weeks apart. Cervical length was measured by standard technique with a covered probe inserted
      into vagina after each woman had emptied her bladder. Excessive pressure on cervix was
      avoided. The mean value of 3 consecutive measurements was used for analysis. Informed consent
      and demographic data were obtained at the enrollment. Primary outcomes were preterm delivery
      before 34 and 37 weeks. Secondary outcomes include time until delivery (latency period,days),
      change of cervical length (cervical attenuation), maternal outcome, neonatal outcome, and
      side effects of drugs were collected. The main outcomes of preterm delivery, gestational age
      at parturition and birthweight were also collected by telephone call in case of
      out-side-hospital born or in case loss to follow up. Monitoring of all patients was evaluated
      every follow up visit for drug side effect, allergic response, and adverse events Statistical
      analysis Sample size was calculated according to the results of two studies by Dorota
      AgataBomba - Opon and Manju Choudhary which showed significant decreased preterm delivery <34
      weeks (9.8% vs 35.3%,p=0.002) in vaginal progesterone group, and significant decreased
      preterm birth (33% vs 58% ; p= 0.034) in oral progesterone group. The sample size of 231 was
      used to evaluate the primary outcome of both drugs. Descriptive statistics were carried out
      using mean, median, standard deviation, interquartile range. Categorical data were tested for
      significance with the χ2tests. Continuous data were evaluated for normal distribution and
      tested for significance with ANOVA and Kruskal-Wallis test. Student t test and Man-Whitney U
      test were used to test significance between groups in case there is significant detection in
      ANOVA and Kruskal-Wallis test among groups. Statistical significance was defined as p<0.05.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Single (Outcomes Assessor)
measure: preterm delivery before 34 and 37 weeks
time frame: 3 months
measure: change of cervical length
time frame: 2 weeks
arm group label: no progesterone
arm group type: No Intervention
description: All women with preterm labor underwent standard tocolysis, which was administered for at least 48 hours, to allow corticosteroid promote fetal lung maturation
arm group label: oral progesterone
arm group type: Experimental
description: All women with preterm labor underwent standard tocolysis, which was administered for at least 48 hours, to allow corticosteroid promote fetal lung maturation. All women in this arm received oral progesterone (dydrogesterone 10 mg; Duphaston™) per oral three times a day
arm group label: vaginal progesterone
arm group type: Experimental
description: All women with preterm labor underwent standard tocolysis, which was administered for at least 48 hours, to allow corticosteroid promote fetal lung maturation. All women in this arm received vaginal progesterone (micronized progesterone 200 mg; Utrogestan™) at bed time.
intervention type: Drug
intervention name: dydrogesterone
arm group label: oral progesterone
other name: Duphaston
intervention type: Drug
intervention name: Micronized progesterone
arm group label: vaginal progesterone
other name: Utrogestan
criteria: 
gender: Female
minimum age: N/A
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Piyawadee Wuttikonsammakit, MD
role: Principal Investigator
affiliation: Instructor
facility: 
country: Thailand
responsible party type: Principal Investigator
investigator affiliation: Sanpasitthiprasong Hospital
investigator full name: Piyawadee Wuttikonsammakit
investigator title: Instructor
mesh term: Premature Birth
mesh term: Obstetric Labor, Premature
mesh term: Progesterone
mesh term: Dydrogesterone
sharing ipd: No