<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/NCT03749902</url>
  </required_header>
  <id_info>
    <org_study_id>4007</org_study_id>
    <nct_id>NCT03749902</nct_id>
  </id_info>
  <brief_title>A Randomized Trial of Oral Misoprostol Alone Versus Oral Misoprostol Followed by Oxytocin for Labour Induction</brief_title>
  <acronym>MOLI</acronym>
  <official_title>A Randomized Trial Comparing Oral Misoprostol Alone With Oral Misoprostol Followed by Oxytocin in Women Induced for Hypertension of Pregnancy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Liverpool</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Gynuity Health Projects</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Government Medical College, Nagpur</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Daga Memorial Women's Hospital, Nagpur, India</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Mahatma Gandhi Institute of Medical Sciences, Sevagram, Wardha, India</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Liverpool</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 primary objective of the trial is to assess the following: In women who have undergone&#xD;
      cervical preparation with oral misoprostol as part of labour induction for hypertensive&#xD;
      disease in India, is augmentation using oral misoprostol superior to the standard protocol of&#xD;
      intravenous oxytocin?&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Every year approximately 30 000 women die from hypertensive disease in pregnancy. Magnesium&#xD;
      sulphate and anti-hypertensives reduce morbidity, but delivery is the only cure. Low dose&#xD;
      oral misoprostol, a prostaglandin E1 analogue, is a highly effective method for labour&#xD;
      induction. Usually, once active labour has commenced, the misoprostol is replaced with an&#xD;
      intravenous oxytocin infusion. However, some studies have shown that oral misoprostol can be&#xD;
      continued into active labour. In the Cochrane review on labour induction, those whose&#xD;
      augmentation was continued with misoprostol (M/M protocol) had 42% less CSs than those who&#xD;
      changed to oxytocin (M/Ox protocol; 15% vs 26%). This misoprostol-only protocol would be&#xD;
      simpler and probably more acceptable to women. However, these two protocols have never been&#xD;
      directly compared. We propose a pragmatic, open-label, randomised trial to compare an M/M&#xD;
      labour induction protocol with the standard M/Ox protocol.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 6, 2020</start_date>
  <completion_date type="Actual">July 30, 2022</completion_date>
  <primary_completion_date type="Actual">July 30, 2022</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Caesarean birth</measure>
    <time_frame>At delivery</time_frame>
    <description>Rate of caesarean birth in the treatment arm</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">520</enrollment>
  <condition>Induction of Labor</condition>
  <arm_group>
    <arm_group_label>Oxytocin infusion</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Oxytocin infusion will be given through an electronic infusion pump. One unit of oxytocin will be injected in 500 mL of Ringer's lactate, started at a rate of 2 mU/min, and increased every 30 min by 2 mU/min until there are three to four contractions every 10 min. The rate will be titrated to maintain that contraction frequency. The maximum dose will be 20mU/min as oxytocin summary product characteristics.&#xD;
The oxytocin group will not receive misoprostol after the membranes have ruptured.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Oral misoprostol</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>An initial dose of misoprostol 25mcg will be given orally after randomisation (this must be a minimum of 2 hours after the previous misoprostol dose).&#xD;
The next dose of oral misoprostol will be omitted if moderate or strong contractions are occurring at 3 in 10 minutes or more (i.e. 9 or more in the preceding 30 minutes)&#xD;
If contractions subsequently reduce to less than 3 in 10 (under 9 in 30 minutes), or become irregular or mild, then the oral misoprostol 25mcg can be restarted&#xD;
In the event of inadequate progress, clinicians will be advised to give further misoprostol if there are any concerns about contractions strength or frequency.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oral misoprostol</intervention_name>
    <description>An initial dose of misoprostol 25mcg will be given orally after randomisation (this must be a minimum of 2 hours after the previous misoprostol dose).&#xD;
The next dose of oral misoprostol will be omitted if moderate or strong contractions are occurring at 3 in 10 minutes or more (i.e. 9 or more in the preceding 30 minutes)&#xD;
If contractions subsequently reduce to less than 3 in 10 (under 9 in 30 minutes), or become irregular or mild, then the oral misoprostol 25mcg can be restarted&#xD;
In the event of inadequate progress, clinicians will be advised to give further misoprostol if there are any concerns about contractions strength or frequency.</description>
    <arm_group_label>Oral misoprostol</arm_group_label>
    <other_name>Misoprost</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxytocin</intervention_name>
    <description>Oxytocin infusion will be given through an electronic infusion pump. One unit of oxytocin will be injected in 500 mL of Ringer's lactate, started at a rate of 2 mU/min, and increased every 30 min by 2 mU/min until there are three to four contractions every 10 min. The rate will be titrated to maintain that contraction frequency. The maximum dose will be 20mU/min as oxytocin summary product characteristics.&#xD;
The oxytocin group will not receive misoprostol after the membranes have ruptured.</description>
    <arm_group_label>Oxytocin infusion</arm_group_label>
    <other_name>Pitocin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  • Ongoing pregnancies with a live fetus who require induction because of preeclampsia&#xD;
             or hypertensionWomen will be included irrespective of whether an intrapartum caesarean&#xD;
             birth on fetal grounds would be considered or not&#xD;
&#xD;
               -  Women age ≥18 years&#xD;
&#xD;
               -  Signed informed consent form&#xD;
&#xD;
               -  Undergone cervical ripening with misoprostol if cervix initially unfavourable&#xD;
&#xD;
               -  Decision to augment labour for inadequate uterine contractions despite ruptured&#xD;
                  membranes (either artificial or spontaneous as part of the induction process)s&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women with previous caesarean births&#xD;
&#xD;
          -  Those unable to give informed consent&#xD;
&#xD;
          -  Cervical ripening with agents other than misoprostol (e.g. Foley catheter,&#xD;
             prostaglandins)&#xD;
&#xD;
          -  Multiple pregnancy&#xD;
&#xD;
          -  History of allergy to misoprostol&#xD;
&#xD;
          -  Adequate uterine activity&#xD;
&#xD;
          -  Pre- induction Ruptured amniotic membranes&#xD;
&#xD;
          -  Frank chorioamnionitis (systemic illness with purulent vaginal discharge and uterine&#xD;
             tenderness)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andrew D Weeks, FRCOG</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Liverpool</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Daga Memorial Women's Hospital</name>
      <address>
        <city>Nagpur</city>
        <state>Maharashtra</state>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mahatma Gandhi Institute of Medical Sciences</name>
      <address>
        <city>Sevagram</city>
        <state>Maharashtra</state>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Government Medical College (GMC)</name>
      <address>
        <city>Nagpur</city>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>November 20, 2018</study_first_submitted>
  <study_first_submitted_qc>November 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 21, 2018</study_first_posted>
  <last_update_submitted>August 5, 2022</last_update_submitted>
  <last_update_submitted_qc>August 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Liverpool</investigator_affiliation>
    <investigator_full_name>Andrew D Weeks</investigator_full_name>
    <investigator_title>Prof of International Maternal Health</investigator_title>
  </responsible_party>
  <keyword>preeclampsia</keyword>
  <keyword>misoprostol</keyword>
  <keyword>oxytocin</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Misoprostol</mesh_term>
    <mesh_term>Oxytocin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The data from this study will be confidential until the database is closed at the end of the study. Following this the study investigators will have exclusive access to the data until the publication of the results in a journal. Once this has happened, the database will be open to other researchers upon request. Open access databases will also be sought so as to maximise the availability of our research data with as few restrictions as possible, in line with MRC and Wellcome Trust policy. The consent form will include a clause for the woman to give permission for her anonymous data to be used for future research studies.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>The data will be released upon publication of the trial results. After this, the data will be shared on a public database to maximise the viability of the data.</ipd_time_frame>
    <ipd_access_criteria>Initially this will be upon request with later public publication of the data.</ipd_access_criteria>
  </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/NCT03749902
org study id: 4007
nct id: NCT03749902
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The primary objective of the trial is to assess the following: In women who have undergone
      cervical preparation with oral misoprostol as part of labour induction for hypertensive
      disease in India, is augmentation using oral misoprostol superior to the standard protocol of
      intravenous oxytocin?
Every year approximately 30 000 women die from hypertensive disease in pregnancy. Magnesium
      sulphate and anti-hypertensives reduce morbidity, but delivery is the only cure. Low dose
      oral misoprostol, a prostaglandin E1 analogue, is a highly effective method for labour
      induction. Usually, once active labour has commenced, the misoprostol is replaced with an
      intravenous oxytocin infusion. However, some studies have shown that oral misoprostol can be
      continued into active labour. In the Cochrane review on labour induction, those whose
      augmentation was continued with misoprostol (M/M protocol) had 42% less CSs than those who
      changed to oxytocin (M/Ox protocol; 15% vs 26%). This misoprostol-only protocol would be
      simpler and probably more acceptable to women. However, these two protocols have never been
      directly compared. We propose a pragmatic, open-label, randomised trial to compare an M/M
      labour induction protocol with the standard M/Ox protocol.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Caesarean birth
time frame: At delivery
description: Rate of caesarean birth in the treatment arm
arm group label: Oxytocin infusion
arm group type: Other
description: Oxytocin infusion will be given through an electronic infusion pump. One unit of oxytocin will be injected in 500 mL of Ringer's lactate, started at a rate of 2 mU/min, and increased every 30 min by 2 mU/min until there are three to four contractions every 10 min. The rate will be titrated to maintain that contraction frequency. The maximum dose will be 20mU/min as oxytocin summary product characteristics.
The oxytocin group will not receive misoprostol after the membranes have ruptured.
arm group label: Oral misoprostol
arm group type: Other
description: An initial dose of misoprostol 25mcg will be given orally after randomisation (this must be a minimum of 2 hours after the previous misoprostol dose).
The next dose of oral misoprostol will be omitted if moderate or strong contractions are occurring at 3 in 10 minutes or more (i.e. 9 or more in the preceding 30 minutes)
If contractions subsequently reduce to less than 3 in 10 (under 9 in 30 minutes), or become irregular or mild, then the oral misoprostol 25mcg can be restarted
In the event of inadequate progress, clinicians will be advised to give further misoprostol if there are any concerns about contractions strength or frequency.
intervention type: Drug
intervention name: Oral misoprostol
description: An initial dose of misoprostol 25mcg will be given orally after randomisation (this must be a minimum of 2 hours after the previous misoprostol dose).
The next dose of oral misoprostol will be omitted if moderate or strong contractions are occurring at 3 in 10 minutes or more (i.e. 9 or more in the preceding 30 minutes)
If contractions subsequently reduce to less than 3 in 10 (under 9 in 30 minutes), or become irregular or mild, then the oral misoprostol 25mcg can be restarted
In the event of inadequate progress, clinicians will be advised to give further misoprostol if there are any concerns about contractions strength or frequency.
arm group label: Oral misoprostol
other name: Misoprost
intervention type: Drug
intervention name: Oxytocin
description: Oxytocin infusion will be given through an electronic infusion pump. One unit of oxytocin will be injected in 500 mL of Ringer's lactate, started at a rate of 2 mU/min, and increased every 30 min by 2 mU/min until there are three to four contractions every 10 min. The rate will be titrated to maintain that contraction frequency. The maximum dose will be 20mU/min as oxytocin summary product characteristics.
The oxytocin group will not receive misoprostol after the membranes have ruptured.
arm group label: Oxytocin infusion
other name: Pitocin
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Andrew D Weeks, FRCOG
role: Principal Investigator
affiliation: University of Liverpool
facility: 
facility: 
facility: 
country: India
responsible party type: Principal Investigator
investigator affiliation: University of Liverpool
investigator full name: Andrew D Weeks
investigator title: Prof of International Maternal Health
mesh term: Misoprostol
mesh term: Oxytocin
sharing ipd: Yes
ipd description: The data from this study will be confidential until the database is closed at the end of the study. Following this the study investigators will have exclusive access to the data until the publication of the results in a journal. Once this has happened, the database will be open to other researchers upon request. Open access databases will also be sought so as to maximise the availability of our research data with as few restrictions as possible, in line with MRC and Wellcome Trust policy. The consent form will include a clause for the woman to give permission for her anonymous data to be used for future research studies.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: The data will be released upon publication of the trial results. After this, the data will be shared on a public database to maximise the viability of the data.
ipd access criteria: Initially this will be upon request with later public publication of the data.