<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/NCT01710566</url>
  </required_header>
  <id_info>
    <org_study_id>1.3.4</org_study_id>
    <nct_id>NCT01710566</nct_id>
  </id_info>
  <brief_title>Misoprostol and Oxytocin in Uniject® for Postpartum Hemorrhage Prevention in Communities</brief_title>
  <official_title>Preventing Postpartum Hemorrhage: Examining Two Strategies for PPH Prevention in Communities: Misoprostol and Oxytocin in Uniject®</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gynuity Health Projects</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Aga Khan Health Services</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Department of Health and Family Welfare, Government of Gujarat</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Gynuity Health Projects</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This community-based cluster Randomised Control Trial will assess the feasibility, cost,&#xD;
      risks and benefits of use of oral Misoprostol and parenteral Oxytocin in Uniject® as&#xD;
      prophylaxis for postpartum hemorrhage (PPH) in community settings. The study will be&#xD;
      conducted in Jamnagar district in Gujarat state in India. The hypothesis is that a program to&#xD;
      deliver oral misoprostol and one to deliver oxytocin via Uniject® will both be effective in&#xD;
      preventing PPH when introduced in community-based settings.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Rationale for Research: Approximately 30% of maternal deaths in India are attributed to&#xD;
      postpartum hemorrhage (PPH). The most common cause of PPH is uterine atony (failure of the&#xD;
      uterus to contract properly after childbirth). Administration of an uterotonic drug as active&#xD;
      management in the third stage of labor (AMTSL) can significantly reduce the rate of PPH.&#xD;
      Oxytocin is considered the drug of choice for prevention of PPH. However, it is not always&#xD;
      feasible to administer parenteral Oxytocin in resource-poor settings given the cold storage,&#xD;
      sterile equipment, skilled personnel, and administration requirements. Recently, Oxytocin in&#xD;
      Uniject®, a pre-filled, non-refillable easy to use device with a single measured dose has&#xD;
      been found to be equally effective and safer and more convenient to use than traditional&#xD;
      needle and syringe.&#xD;
&#xD;
      Misoprostol has been explored for preventing PPH in settings where parenteral uterotonics are&#xD;
      not yet available or feasible to use. In 2007, the World Health Organisation in its&#xD;
      guidelines on prevention of PPH endorsed the administration of oral Misoprostol for PPH&#xD;
      prevention by unskilled providers &quot;trained in its use in settings where Active management of&#xD;
      the third stage of labor (AMTSL) is not practiced&quot;.&#xD;
&#xD;
      In spite of the evidence of clinical safety and efficacy of oral Misoprostol and/or Oxytocin&#xD;
      in Uniject® as universal PPH prevention drugs, to date, there have been no studies comparing&#xD;
      the programmatic effectiveness of either technology on a large scale or in nationwide PPH&#xD;
      prevention programs. To address this gap, the investigators plan to conduct a large&#xD;
      community-based trial in collaboration with the Aga Khan Health Services, India.&#xD;
&#xD;
      Study Objectives: The study will assess the feasibility, cost, risks and benefits of use of&#xD;
      oral Misoprostol and parenteral Oxytocin in Uniject® as prophylaxis for PPH in community&#xD;
      settings.&#xD;
&#xD;
      Study Design: The study is designed as a community-based cluster Randomised Control Trial.&#xD;
      The study will enroll women delivering at Primary Health Centres (PHCs). Study centres will&#xD;
      be assigned to one of the following: Group 1: 600 mcg oral Misoprostol, Group 2: 10 IU IM&#xD;
      Oxytocin delivered by Uniject®.&#xD;
&#xD;
      Study Procedures&#xD;
&#xD;
        1. Informed consent /Enrollment: Women will be approached by trained study staff in the&#xD;
           third trimester or when they present for delivery and asked if they wish to participate&#xD;
           in the study. Women who meet the study's eligibility criteria and agree to participate&#xD;
           will be asked to provide written consent. After enrollment, their baseline data will be&#xD;
           recorded and a pre-delivery hemoglobin assessment will be done.&#xD;
&#xD;
        2. At time of delivery: Standard procedures to manage the delivery will be followed.&#xD;
           Immediately after delivery, participants will be given the assigned study medication&#xD;
           (either Misoprostol or Oxytocin by Uniject®). The provider will monitor the women for&#xD;
           side effects for 1 - 2 hours after delivery. Referrals will be carried out as per&#xD;
           standard of care in each setting and documented.&#xD;
&#xD;
        3. After delivery: The follow up visit will be conducted by a trained community health&#xD;
           worker. Post-delivery Hb will be recorded for all women approximately 72 hours after&#xD;
           delivery. Women's experiences of side effects, and acceptability and satisfaction with&#xD;
           her care will be documented.&#xD;
&#xD;
      Study Site and Sample: The study will be conducted in the Jamnagar district in Gujarat,India.&#xD;
      Twenty seven PHCs will be considered eligible for participation. To detect a significant&#xD;
      difference (pre- to post-delivery Hb) between the two prophylactic regimens of 0.1 g/dL (SD&#xD;
      0.3 g/dL), and also adjusting for the cluster design, a total sample of approximately 1500&#xD;
      deliveries is planned(750 deliveries per group).&#xD;
&#xD;
      Study Medications: Both the drugs and Uniject device will be obtained from a pharmaceutical&#xD;
      company in compliance with good manufacturing procedures. Gynuity will be responsible for&#xD;
      supplying and re-supplying both the medications throughout the study and will monitor all&#xD;
      logistics related to supply.&#xD;
&#xD;
      Ethical considerations: Both the drugs are safe, effective evidence-based prophylactic&#xD;
      uterotonics to prevent PPH. However, the protocol will be approved by all relevant&#xD;
      Institutional Review Boards prior to enrollment of study participants. Only authorized study&#xD;
      personnel will have access to study supplies and documents.&#xD;
&#xD;
      Monitoring and Evaluation: An independent data and safety monitoring board will review the&#xD;
      data periodically and make recommendations to investigators concerning study modification, if&#xD;
      needed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <start_date>July 2013</start_date>
  <completion_date type="Anticipated">December 2014</completion_date>
  <primary_completion_date type="Anticipated">December 2014</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 (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean change in Pre- and post-delivery Haemoglobin</measure>
    <time_frame>18 months</time_frame>
    <description>To establish the comparable effectiveness of two programmatic strategies, individual pre- and post-delivery Hb measures will be taken to calculate change in Hb. This will be done using a Hemocue Hemoglobin machine + cuvette (HemoCue, Angelholm, Sweden). The Hemocue is a simple means of collecting Hb measures at the community-level where traditional laboratory techniques are not feasible.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety</measure>
    <time_frame>18 months</time_frame>
    <description>Occurrence and management of side effects, timing of drug administration and serious adverse outcomes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical effectiveness</measure>
    <time_frame>18 months</time_frame>
    <description>Change in hemoglobin ≥ 2 g/dL, prolonged third stage of labor, any additional interventions carried out.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Programmatic feasibility</measure>
    <time_frame>18 months</time_frame>
    <description>Acceptability among women and providers,drug accountability, disposal and management, any problems to report, refusals or complaints by women or their families</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cost-effectiveness</measure>
    <time_frame>18 months</time_frame>
    <description>Costs of supplies, wastage, refresher trainings, storage and transportation, referrals and management of side effects will be assessed.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Postpartum Hemorrhage</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>600 mcg oral misoprostol</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 IU oxytocin in Uniject</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Misoprostol</intervention_name>
    <description>600 mcg oral misoprostol to be administered after delivery of baby and before placenta is expelled</description>
    <arm_group_label>Group 1</arm_group_label>
    <other_name>Misoprost</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxytocin</intervention_name>
    <description>10 IU oxytocin in Uniject will be administered after delivery of baby and before placenta is expelled</description>
    <arm_group_label>Group 2</arm_group_label>
    <other_name>Oxytocin in Uniject</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pregnant women planning vaginal delivery with a trained study provider at a PHC who&#xD;
             are eligible to participate in research according to national guidelines and able to&#xD;
             provide informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women not delivering in study catchment area with a trained study provider will not be&#xD;
             eligible to participate in the trial.&#xD;
&#xD;
          -  Women with known contraindications to prostaglandins, including misoprostol will also&#xD;
             be excluded.&#xD;
&#xD;
          -  Women delivering in a facility that currently routinely administers prophylactic&#xD;
             oxytocin to women in the third stage labor will also be excluded.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>February 2016</verification_date>
  <study_first_submitted>May 8, 2012</study_first_submitted>
  <study_first_submitted_qc>October 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 19, 2012</study_first_posted>
  <last_update_submitted>February 12, 2016</last_update_submitted>
  <last_update_submitted_qc>February 12, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 15, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Postpartum hemorrhage</keyword>
  <keyword>prevention</keyword>
  <keyword>oxytocin</keyword>
  <keyword>misoprostol</keyword>
  <keyword>Uniject</keyword>
  <keyword>community</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Postpartum Hemorrhage</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
  </condition_browse>
  <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>
  <!-- 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/NCT01710566
org study id: 1.3.4
nct id: NCT01710566
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
This community-based cluster Randomised Control Trial will assess the feasibility, cost,
      risks and benefits of use of oral Misoprostol and parenteral Oxytocin in Uniject® as
      prophylaxis for postpartum hemorrhage (PPH) in community settings. The study will be
      conducted in Jamnagar district in Gujarat state in India. The hypothesis is that a program to
      deliver oral misoprostol and one to deliver oxytocin via Uniject® will both be effective in
      preventing PPH when introduced in community-based settings.
Rationale for Research: Approximately 30% of maternal deaths in India are attributed to
      postpartum hemorrhage (PPH). The most common cause of PPH is uterine atony (failure of the
      uterus to contract properly after childbirth). Administration of an uterotonic drug as active
      management in the third stage of labor (AMTSL) can significantly reduce the rate of PPH.
      Oxytocin is considered the drug of choice for prevention of PPH. However, it is not always
      feasible to administer parenteral Oxytocin in resource-poor settings given the cold storage,
      sterile equipment, skilled personnel, and administration requirements. Recently, Oxytocin in
      Uniject®, a pre-filled, non-refillable easy to use device with a single measured dose has
      been found to be equally effective and safer and more convenient to use than traditional
      needle and syringe.

      Misoprostol has been explored for preventing PPH in settings where parenteral uterotonics are
      not yet available or feasible to use. In 2007, the World Health Organisation in its
      guidelines on prevention of PPH endorsed the administration of oral Misoprostol for PPH
      prevention by unskilled providers "trained in its use in settings where Active management of
      the third stage of labor (AMTSL) is not practiced".

      In spite of the evidence of clinical safety and efficacy of oral Misoprostol and/or Oxytocin
      in Uniject® as universal PPH prevention drugs, to date, there have been no studies comparing
      the programmatic effectiveness of either technology on a large scale or in nationwide PPH
      prevention programs. To address this gap, the investigators plan to conduct a large
      community-based trial in collaboration with the Aga Khan Health Services, India.

      Study Objectives: The study will assess the feasibility, cost, risks and benefits of use of
      oral Misoprostol and parenteral Oxytocin in Uniject® as prophylaxis for PPH in community
      settings.

      Study Design: The study is designed as a community-based cluster Randomised Control Trial.
      The study will enroll women delivering at Primary Health Centres (PHCs). Study centres will
      be assigned to one of the following: Group 1: 600 mcg oral Misoprostol, Group 2: 10 IU IM
      Oxytocin delivered by Uniject®.

      Study Procedures

        1. Informed consent /Enrollment: Women will be approached by trained study staff in the
           third trimester or when they present for delivery and asked if they wish to participate
           in the study. Women who meet the study's eligibility criteria and agree to participate
           will be asked to provide written consent. After enrollment, their baseline data will be
           recorded and a pre-delivery hemoglobin assessment will be done.

        2. At time of delivery: Standard procedures to manage the delivery will be followed.
           Immediately after delivery, participants will be given the assigned study medication
           (either Misoprostol or Oxytocin by Uniject®). The provider will monitor the women for
           side effects for 1 - 2 hours after delivery. Referrals will be carried out as per
           standard of care in each setting and documented.

        3. After delivery: The follow up visit will be conducted by a trained community health
           worker. Post-delivery Hb will be recorded for all women approximately 72 hours after
           delivery. Women's experiences of side effects, and acceptability and satisfaction with
           her care will be documented.

      Study Site and Sample: The study will be conducted in the Jamnagar district in Gujarat,India.
      Twenty seven PHCs will be considered eligible for participation. To detect a significant
      difference (pre- to post-delivery Hb) between the two prophylactic regimens of 0.1 g/dL (SD
      0.3 g/dL), and also adjusting for the cluster design, a total sample of approximately 1500
      deliveries is planned(750 deliveries per group).

      Study Medications: Both the drugs and Uniject device will be obtained from a pharmaceutical
      company in compliance with good manufacturing procedures. Gynuity will be responsible for
      supplying and re-supplying both the medications throughout the study and will monitor all
      logistics related to supply.

      Ethical considerations: Both the drugs are safe, effective evidence-based prophylactic
      uterotonics to prevent PPH. However, the protocol will be approved by all relevant
      Institutional Review Boards prior to enrollment of study participants. Only authorized study
      personnel will have access to study supplies and documents.

      Monitoring and Evaluation: An independent data and safety monitoring board will review the
      data periodically and make recommendations to investigators concerning study modification, if
      needed.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Single (Participant)
measure: Mean change in Pre- and post-delivery Haemoglobin
time frame: 18 months
description: To establish the comparable effectiveness of two programmatic strategies, individual pre- and post-delivery Hb measures will be taken to calculate change in Hb. This will be done using a Hemocue Hemoglobin machine + cuvette (HemoCue, Angelholm, Sweden). The Hemocue is a simple means of collecting Hb measures at the community-level where traditional laboratory techniques are not feasible.
measure: Safety
time frame: 18 months
description: Occurrence and management of side effects, timing of drug administration and serious adverse outcomes
measure: Clinical effectiveness
time frame: 18 months
description: Change in hemoglobin ≥ 2 g/dL, prolonged third stage of labor, any additional interventions carried out.
measure: Programmatic feasibility
time frame: 18 months
description: Acceptability among women and providers,drug accountability, disposal and management, any problems to report, refusals or complaints by women or their families
measure: Cost-effectiveness
time frame: 18 months
description: Costs of supplies, wastage, refresher trainings, storage and transportation, referrals and management of side effects will be assessed.
arm group label: Group 1
arm group type: Experimental
description: 600 mcg oral misoprostol
arm group label: Group 2
arm group type: Experimental
description: 10 IU oxytocin in Uniject
intervention type: Drug
intervention name: Misoprostol
description: 600 mcg oral misoprostol to be administered after delivery of baby and before placenta is expelled
arm group label: Group 1
other name: Misoprost
intervention type: Drug
intervention name: Oxytocin
description: 10 IU oxytocin in Uniject will be administered after delivery of baby and before placenta is expelled
arm group label: Group 2
other name: Oxytocin in Uniject
criteria: 
gender: Female
minimum age: N/A
maximum age: N/A
healthy volunteers: No
responsible party type: Sponsor
mesh term: Postpartum Hemorrhage
mesh term: Hemorrhage
mesh term: Misoprostol
mesh term: Oxytocin