<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/NCT04413890</url>
  </required_header>
  <id_info>
    <org_study_id>19_RIPH2_10</org_study_id>
    <nct_id>NCT04413890</nct_id>
  </id_info>
  <brief_title>Comparison of Two Rhythm of Administration of Prostaglandin Gel for Induction of Labor</brief_title>
  <acronym>GELFREQ</acronym>
  <official_title>Administration of Prostaglandin Gel for Cervical Priming During Induction of Labour Every 12 Hours Versus 24 Hours: a Randomized Superiority Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital Center of Martinique</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital Center of Martinique</source>
  <oversight_info>
    <has_dmc>Yes</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 study compares two rhythms of administration of prostaglandin vaginal gels for cervical&#xD;
      priming before induction of labor in term patients. In our institution, prostaglandin gels&#xD;
      are given for a maximum of three times, with induction by oxytocin and amniotomy the day&#xD;
      after the last gel whatever Bishop score has been obtained. This management results in some&#xD;
      patient spending four days in hospital before delivery. The aim of the study is to compare&#xD;
      our classical management scheme with a reduced interval between to gels, of 12h instead of 24&#xD;
      h. The primary outcome will be the time elapsed between the first prostaglandin gel and&#xD;
      delivery. Tolerance of both management patterns will also be evaluated through a satisfaction&#xD;
      survey.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Approximatively 22% of pregnant women have an induction of labor in France (22.9% in our&#xD;
      institution in 2019), mainly for prolonged pregnancy after 41 weeks gestational age or&#xD;
      prolonged rupture of membranes. Patients whose cervix is considered unripe (Bishop score&#xD;
      under 6) are generally proposed a cervical priming because induction of labor without prior&#xD;
      priming entails a higher of cesarean delivery rate for failed induction. The devices used for&#xD;
      cervical priming are pharmacological (mainly prostaglandin gel, pessaries or suppositories)&#xD;
      or mechanical (Foley catheter, Cook balloons). Very few recommendations exist regarding the&#xD;
      type of device, the rhythm and maximal number of repeat administrations and the interval&#xD;
      between two administrations. Shortening interval between two administrations (in case of use&#xD;
      of a device necessitating serial prescriptions) may shorten the time interval between&#xD;
      beginning of priming and delivery. In our institution, a vaginal gel can be given three times&#xD;
      before induction of labor with oxytocin and amniotomy, whatever Bishop score has been&#xD;
      obtained after priming. These gels are given on a daily basis. This rhythm implies than for&#xD;
      some women not responding to a first gel, priming can last up to three days, lengthening&#xD;
      hospital stay and leading to maternal weariness. Maternal satisfaction during induction of&#xD;
      labor is seldom analyzed. An intensification in gel administration implies a change in&#xD;
      maternal management during the induction process, with shortened periods of rest between two&#xD;
      gels and nearer periods of pain and discomfort, albeit on a theoretically shorter period. The&#xD;
      way patients deal with this new rhythm compared to the classical in part of the evaluation in&#xD;
      this study. All patients having a singleton pregnancy and an indication for term (≥ 37 weeks&#xD;
      gestation age) induction with an unfavorable cervix and no contraindication to vaginal&#xD;
      delivery will be eligible. Patients with fetuses in breech presentation, a scarred uterus,&#xD;
      under 18 years, bearing a fetus with antenatally known malformation, not fluent in French or&#xD;
      presenting an allergy to prostaglandins will be excluded. A written informed consent will be&#xD;
      required before inclusion. The primary outcome will be the duration between first priming&#xD;
      with prostaglandin gel and delivery. Secondary outcomes will be the satisfaction of patients&#xD;
      with their induction process (measured through a survey answered during the in-hospital&#xD;
      post-partum stay), the rate of cesarean section, the rate of hypertonia/hypercinesia during&#xD;
      priming and induction requiring medical intervention, the length of active phase of labor&#xD;
      (after 5 cm of dilation), the oxytocin doses used during delivery for induction or&#xD;
      augmentation, initial neonatal (Apgar score, arterial cord pH and lactates, resuscitation&#xD;
      maneuvers, transfer to intensive care unit) and maternal (post-partum hemorrhage,&#xD;
      hyperthermia during labor, perineal laceration &gt; 2nd degree and endometritis) morbidity and&#xD;
      length of total hospital stay. The investigators calculated that a sample of 268 patients&#xD;
      (134 in each group) will be necessary to detect a 30% reduction in duration between first&#xD;
      priming and delivery in the experimental group (one gel every 12h) compared with the&#xD;
      classical group. Mean time frame between first priming and delivery has been measured in our&#xD;
      department in 2018 to 31.8 hours (standard deviation 27.6 hours).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 17, 2019</start_date>
  <completion_date type="Actual">January 27, 2021</completion_date>
  <primary_completion_date type="Actual">January 27, 2021</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>Time between gel administration and delivery</measure>
    <time_frame>At inclusion (Day 0)</time_frame>
    <description>Time between first gel administration for cervical priming and delivery</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time between gel administration and delivery</measure>
    <time_frame>At 12 hours or 24 hours (after each gel administration)</time_frame>
    <description>Change between cervical priming and delivery</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time between gel administration and delivery</measure>
    <time_frame>Time 0 after the childbirth</time_frame>
    <description>Time between first gel administration for cervical priming and delivery</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time between gel administration and delivery</measure>
    <time_frame>Until 5 days postpartum (during in-hospital postpartum period)</time_frame>
    <description>Time between first gel administration for cervical priming and delivery</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maternal satisfaction</measure>
    <time_frame>Until 5 days postpartum</time_frame>
    <description>maternal satisfaction measured by survey self-administered during postpartum hospital stay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cesarean section rate</measure>
    <time_frame>During labor</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hypertonia / hypercinesia rate</measure>
    <time_frame>During priming and induction</time_frame>
    <description>Hypertonia (rise of uterus tone more than 10 minutes)/hypercinesia (more than 5 uterine contractions per 10 minutes) rate during priming and induction</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oxytocin dose during labor</measure>
    <time_frame>During labor</time_frame>
    <description>Induction or augmentation of Oxytocin doses</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of active first phase of labor</measure>
    <time_frame>During labor</time_frame>
    <description>Induction or augmentation of active first phase of labor</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maternal morbidity</measure>
    <time_frame>During labor</time_frame>
    <description>Fever during labor, perineal laceration superior to 2nd degree, postpartum hemorrhage, endometritis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neonatal immediate morbidity</measure>
    <time_frame>5 minutes after childbirth</time_frame>
    <description>Assess if Apgar score is less than 7</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neonatal immediate morbidity</measure>
    <time_frame>5 minutes after childbirth</time_frame>
    <description>Assess of arterial cord pH level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neonatal immediate morbidity</measure>
    <time_frame>5 minutes after childbirth</time_frame>
    <description>Assess of arterial cord lactate level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neonatal immediate morbidity</measure>
    <time_frame>5 minutes after childbirth</time_frame>
    <description>Concentration of arterial cord lactates level (in Mmol/L)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neonatal immediate morbidity</measure>
    <time_frame>5 minutes after childbirth</time_frame>
    <description>Occurence or not of resuscitation maneuvers in delivery room</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neonatal immediate morbidity</measure>
    <time_frame>5 minutes after childbirth</time_frame>
    <description>Occurence or no transfer of the child to neonatal intensive care unit</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">268</enrollment>
  <condition>Labor Complication</condition>
  <condition>Cervix</condition>
  <arm_group>
    <arm_group_label>Classical administration</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>One prostaglandin vaginal gel every 24 hours</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Experimental administration</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>One prostaglandin vaginal gel every 12 hours</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dinoprostone vaginal gel</intervention_name>
    <description>Prostaglandin gel 0.5, 1 or 2 mg</description>
    <arm_group_label>Classical administration</arm_group_label>
    <arm_group_label>Experimental administration</arm_group_label>
    <other_name>cervical priming with prostaglandin gel</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients above 18 years&#xD;
&#xD;
          -  Gestational age ≥ 37 weeks&#xD;
&#xD;
          -  With indicated induction of labor and initial Bishop score under 6&#xD;
&#xD;
          -  Without any contraindication to vaginal delivery&#xD;
&#xD;
          -  Who consent to participate to the clinical research&#xD;
&#xD;
          -  With French Medical Public Insurance&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Multiple pregnancy&#xD;
&#xD;
          -  Previous uterine scar (for myomas or cesarean section)&#xD;
&#xD;
          -  Fetus not in cephalic presentation&#xD;
&#xD;
          -  Allergy to prostaglandins&#xD;
&#xD;
          -  Who not consent to participate to the study&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>pregnant women</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>49 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jean-Luc VOLUMENIE</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital of Martinique</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital of Martinique</name>
      <address>
        <city>Fort-de-France</city>
        <zip>97261</zip>
        <country>Martinique</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Martinique</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>April 7, 2020</study_first_submitted>
  <study_first_submitted_qc>May 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>July 18, 2023</last_update_submitted>
  <last_update_submitted_qc>July 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 19, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Induction</keyword>
  <keyword>Term</keyword>
  <keyword>Labor</keyword>
  <keyword>Rhythm</keyword>
  <keyword>Prostaglandins</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Obstetric Labor Complications</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dinoprostone</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/NCT04413890
org study id: 19_RIPH2_10
nct id: NCT04413890
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The study compares two rhythms of administration of prostaglandin vaginal gels for cervical
      priming before induction of labor in term patients. In our institution, prostaglandin gels
      are given for a maximum of three times, with induction by oxytocin and amniotomy the day
      after the last gel whatever Bishop score has been obtained. This management results in some
      patient spending four days in hospital before delivery. The aim of the study is to compare
      our classical management scheme with a reduced interval between to gels, of 12h instead of 24
      h. The primary outcome will be the time elapsed between the first prostaglandin gel and
      delivery. Tolerance of both management patterns will also be evaluated through a satisfaction
      survey.
Approximatively 22% of pregnant women have an induction of labor in France (22.9% in our
      institution in 2019), mainly for prolonged pregnancy after 41 weeks gestational age or
      prolonged rupture of membranes. Patients whose cervix is considered unripe (Bishop score
      under 6) are generally proposed a cervical priming because induction of labor without prior
      priming entails a higher of cesarean delivery rate for failed induction. The devices used for
      cervical priming are pharmacological (mainly prostaglandin gel, pessaries or suppositories)
      or mechanical (Foley catheter, Cook balloons). Very few recommendations exist regarding the
      type of device, the rhythm and maximal number of repeat administrations and the interval
      between two administrations. Shortening interval between two administrations (in case of use
      of a device necessitating serial prescriptions) may shorten the time interval between
      beginning of priming and delivery. In our institution, a vaginal gel can be given three times
      before induction of labor with oxytocin and amniotomy, whatever Bishop score has been
      obtained after priming. These gels are given on a daily basis. This rhythm implies than for
      some women not responding to a first gel, priming can last up to three days, lengthening
      hospital stay and leading to maternal weariness. Maternal satisfaction during induction of
      labor is seldom analyzed. An intensification in gel administration implies a change in
      maternal management during the induction process, with shortened periods of rest between two
      gels and nearer periods of pain and discomfort, albeit on a theoretically shorter period. The
      way patients deal with this new rhythm compared to the classical in part of the evaluation in
      this study. All patients having a singleton pregnancy and an indication for term (≥ 37 weeks
      gestation age) induction with an unfavorable cervix and no contraindication to vaginal
      delivery will be eligible. Patients with fetuses in breech presentation, a scarred uterus,
      under 18 years, bearing a fetus with antenatally known malformation, not fluent in French or
      presenting an allergy to prostaglandins will be excluded. A written informed consent will be
      required before inclusion. The primary outcome will be the duration between first priming
      with prostaglandin gel and delivery. Secondary outcomes will be the satisfaction of patients
      with their induction process (measured through a survey answered during the in-hospital
      post-partum stay), the rate of cesarean section, the rate of hypertonia/hypercinesia during
      priming and induction requiring medical intervention, the length of active phase of labor
      (after 5 cm of dilation), the oxytocin doses used during delivery for induction or
      augmentation, initial neonatal (Apgar score, arterial cord pH and lactates, resuscitation
      maneuvers, transfer to intensive care unit) and maternal (post-partum hemorrhage,
      hyperthermia during labor, perineal laceration > 2nd degree and endometritis) morbidity and
      length of total hospital stay. The investigators calculated that a sample of 268 patients
      (134 in each group) will be necessary to detect a 30% reduction in duration between first
      priming and delivery in the experimental group (one gel every 12h) compared with the
      classical group. Mean time frame between first priming and delivery has been measured in our
      department in 2018 to 31.8 hours (standard deviation 27.6 hours).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Time between gel administration and delivery
time frame: At inclusion (Day 0)
description: Time between first gel administration for cervical priming and delivery
measure: Time between gel administration and delivery
time frame: At 12 hours or 24 hours (after each gel administration)
description: Change between cervical priming and delivery
measure: Time between gel administration and delivery
time frame: Time 0 after the childbirth
description: Time between first gel administration for cervical priming and delivery
measure: Time between gel administration and delivery
time frame: Until 5 days postpartum (during in-hospital postpartum period)
description: Time between first gel administration for cervical priming and delivery
measure: Maternal satisfaction
time frame: Until 5 days postpartum
description: maternal satisfaction measured by survey self-administered during postpartum hospital stay
measure: Cesarean section rate
time frame: During labor
measure: Hypertonia / hypercinesia rate
time frame: During priming and induction
description: Hypertonia (rise of uterus tone more than 10 minutes)/hypercinesia (more than 5 uterine contractions per 10 minutes) rate during priming and induction
measure: Oxytocin dose during labor
time frame: During labor
description: Induction or augmentation of Oxytocin doses
measure: Length of active first phase of labor
time frame: During labor
description: Induction or augmentation of active first phase of labor
measure: Maternal morbidity
time frame: During labor
description: Fever during labor, perineal laceration superior to 2nd degree, postpartum hemorrhage, endometritis
measure: Neonatal immediate morbidity
time frame: 5 minutes after childbirth
description: Assess if Apgar score is less than 7
measure: Neonatal immediate morbidity
time frame: 5 minutes after childbirth
description: Assess of arterial cord pH level
measure: Neonatal immediate morbidity
time frame: 5 minutes after childbirth
description: Assess of arterial cord lactate level
measure: Neonatal immediate morbidity
time frame: 5 minutes after childbirth
description: Concentration of arterial cord lactates level (in Mmol/L)
measure: Neonatal immediate morbidity
time frame: 5 minutes after childbirth
description: Occurence or not of resuscitation maneuvers in delivery room
measure: Neonatal immediate morbidity
time frame: 5 minutes after childbirth
description: Occurence or no transfer of the child to neonatal intensive care unit
arm group label: Classical administration
arm group type: Active Comparator
description: One prostaglandin vaginal gel every 24 hours
arm group label: Experimental administration
arm group type: Experimental
description: One prostaglandin vaginal gel every 12 hours
intervention type: Drug
intervention name: Dinoprostone vaginal gel
description: Prostaglandin gel 0.5, 1 or 2 mg
arm group label: Classical administration
arm group label: Experimental administration
other name: cervical priming with prostaglandin gel
criteria: 
gender: Female
gender based: Yes
gender description: pregnant women
minimum age: 18 Years
maximum age: 49 Years
healthy volunteers: No
last name: Jean-Luc VOLUMENIE
role: Principal Investigator
affiliation: University Hospital of Martinique
facility: 
country: Martinique
responsible party type: Sponsor
mesh term: Obstetric Labor Complications
mesh term: Dinoprostone