<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/NCT02970552</url>
  </required_header>
  <id_info>
    <org_study_id>16-2174</org_study_id>
    <secondary_id>1R21HD090987-01</secondary_id>
    <secondary_id>Z 31606</secondary_id>
    <nct_id>NCT02970552</nct_id>
  </id_info>
  <brief_title>Feasibility of Vaginal Progesterone to Reduce HIV-Associated Preterm Birth</brief_title>
  <acronym>VP</acronym>
  <official_title>A Pilot Study of Vaginal Progesterone to Reduce Preterm Birth Among Women Receiving Antiretroviral Therapy in Pregnancy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of North Carolina, Chapel Hill</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of North Carolina, Chapel Hill</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      More than 1.5 million HIV-infected women become pregnant each year. Approximately half have&#xD;
      access to antiretroviral therapy (ART), but all are at increased risk of preterm birth (PTB).&#xD;
      Vaginal progesterone (VP) is a promising and cost-effective intervention to prevent PTB that&#xD;
      should be studied in this high-risk population. This pilot study will provide critical&#xD;
      insight into the feasibility of a phase III trial by determining whether women are willing to&#xD;
      participate, to adhere to study drug, and to complete follow-up.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be a mixed method study to evaluate the feasibility and acceptability of a trial of&#xD;
      VP to prevent PTB among HIV-infected Zambian women. To assess the feasibility of a full-scale&#xD;
      clinical trial, the investigators will implement a pilot two-arm, double-masked,&#xD;
      placebo-controlled trial of VP among HIV-infected women in antenatal care in Lusaka, Zambia.&#xD;
      Participants will be randomly assigned to either daily self-administered VP or&#xD;
      indistinguishable placebo prior to 24 weeks gestational age. In this pilot study, the&#xD;
      investigators will be able to estimate study uptake, adherence to study product and protocol,&#xD;
      and study retention. To assess the acceptability of a trial to test VP among HIV-infected&#xD;
      women in Zambia, the investigators will employ a qualitative approach of longitudinal&#xD;
      semi-structured interviews among women agreeing to trial participation and one-time&#xD;
      semi-structured interviews (SSIs) among those who decline to participate.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2017</start_date>
  <completion_date type="Actual">November 13, 2018</completion_date>
  <primary_completion_date type="Actual">November 13, 2018</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>Prevention</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adequate Adherence to Study Product</measure>
    <time_frame>Enrollment through 36th gestational week, an overall total of up to 17 weeks</time_frame>
    <description>Number of participants who achieved adequate adherence to study product, defined as proper self-administration of at least 80% of prescribed study product doses, as measured by a dye stain assay of returned applicators</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Acceptability of Use of Vaginal Progesterone (VP)</measure>
    <time_frame>At enrollment (20-24 weeks gestation), at 28 weeks gestation, and at 36 weeks gestation</time_frame>
    <description>Semi-structured interviews will be held with a random sample of participants who enroll and those who decline enrollment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reported Barriers and Facilitators to Adherence to Study Product, Returning Used Applicators, and Retention in the Study</measure>
    <time_frame>Late in pregnancy or postpartum</time_frame>
    <description>Number of participants reporting barriers and facilitators to study product adherence, returning used applicators, and retention in the study during a semi-structured interview. Participants were selected for an interview based on their overall adherence rates, including those with excellent adherence throughout the study and those with lower adherence rates early or late in their participation. A trained female staff member conducted each 30-minute interview using an interview guide. Interviews were audiotaped, transcribed, and translated into English as necessary.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Summary of Reported Knowledge, Attitudes, and Practices Related to HIV, Antiretroviral Therapy (ART), Risk of Preterm Birth, and Participation in Placebo Controlled Randomized Clinical Trials (RCTs)</measure>
    <time_frame>Late in pregnancy or postpartum</time_frame>
    <description>Number of participants reporting attitudes and practices related to participation in placebo controlled RCTs during a semi-structured interview. Participants were selected for an interview based on their overall adherence rates, including those with excellent adherence throughout the study and those with lower adherence rates early or late in their participation. A trained female staff member conducted each 30-minute interview using an interview guide. Participants were asked about their attitudes toward participation in the study and research in general as HIV-infected women taking ART and at risk of preterm birth, but they were not specifically asked about their underlying knowledge of these conditions. Interviews were audio-taped, transcribed, and translated into English as necessary.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acceptability of a Vaginal Medication to Prevent Preterm Birth</measure>
    <time_frame>Visit 9.0 (36 weeks of gestation)</time_frame>
    <description>Number of participants reporting specific attitudes about medications for the prevention of preterm birth (PTB), including acceptability of daily vaginal administration as measured on the Exit Satisfaction Survey using a Likert scale of five possible options ranging from strongly agree to strongly disagree. The form included a range of facial illustrations to facilitate comprehension of the answer choices, particularly for illiterate participants.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reported Barriers to Adherence to Study Product</measure>
    <time_frame>Visit 9.0 (36 weeks of gestation)</time_frame>
    <description>Number of participants reporting challenges with taking the study medication as measured on the Exit Satisfaction Survey. The survey was administered by a study nurse who asked each participant what was the hardest part about taking the medication and presented all possible answer choices. Participant were asked to select only one answer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sensitivity, Specificity, and Predictive Value of Dose Diaries</measure>
    <time_frame>Enrollment through 36th gestational week, an overall total of up to 17 weeks</time_frame>
    <description>Comparison of self-reported adherence rates (Dose Diary/DD) and use of returned applicators measured by dye stain assay (DSA)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Enrollment of Eligible Participants</measure>
    <time_frame>Screening through Enrollment</time_frame>
    <description>Number of eligible participants who enrolled in the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ascertainment of Date of Delivery and Infant Vital Status</measure>
    <time_frame>Visit 10.0 (Delivery)</time_frame>
    <description>Number of women for whom date of delivery and infant vital status at birth was ascertained</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Preliminary Efficacy</measure>
    <time_frame>Visit 10.0 (Delivery)</time_frame>
    <description>Number of participants delivering before 34 and 37 completed weeks of gestation, grouped based on whether the participant went into labor spontaneously or was induced by a provider</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Birth Weight</measure>
    <time_frame>Visit 10.0 (Delivery)</time_frame>
    <description>Number of participants with neonates weighing less than 2500 grams at birth</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stillbirth</measure>
    <time_frame>Visit 10.0 (Delivery)</time_frame>
    <description>Number of participants who experienced a stillbirth</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>Enrollment through Visit 10.0 (Delivery)</time_frame>
    <description>Number of women experiencing a serious adverse event or event that resulted in study product discontinuation</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">140</enrollment>
  <condition>PreTerm Birth</condition>
  <arm_group>
    <arm_group_label>Vaginal Progesterone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Daily self-administered vaginal progesterone</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Daily self-administered indistinguishable placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vaginal Progesterone</intervention_name>
    <description>200 mg micronized vaginal progesterone suppository</description>
    <arm_group_label>Vaginal Progesterone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Indistinguishable placebo vaginal suppository</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. 18 years of age or older&#xD;
&#xD;
          2. viable intrauterine pregnancy confirmed by ultrasound&#xD;
&#xD;
          3. presentation to antenatal care prior to 24 weeks gestation&#xD;
&#xD;
          4. antibody-confirmed HIV-1 infection&#xD;
&#xD;
          5. initiating or continuing ART treatment in pregnancy&#xD;
&#xD;
          6. ability and willingness to provide written informed consent&#xD;
&#xD;
          7. willing to adhere to study visit schedule&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. multiple gestation&#xD;
&#xD;
          2. non-research indication for antenatal progesterone (i.e. prior spontaneous PTB and/or&#xD;
             cervical length &lt;20mm on screening ultrasound)&#xD;
&#xD;
          3. planned or in situ cervical cerclage&#xD;
&#xD;
          4. evidence of threatened abortion, preterm labor, or ruptured membranes&#xD;
&#xD;
          5. major fetal anomaly detected on screening ultrasound&#xD;
&#xD;
          6. known uterine anomaly&#xD;
&#xD;
          7. known or suspected allergy or contraindication to VP or placebo components&#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>Jeffrey Stringer, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of North Carolina, Chapel Hill</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Kamwala District Health Centre</name>
      <address>
        <city>Lusaka</city>
        <country>Zambia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Zambia</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>November 17, 2016</study_first_submitted>
  <study_first_submitted_qc>November 18, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 22, 2016</study_first_posted>
  <results_first_submitted>November 14, 2019</results_first_submitted>
  <results_first_submitted_qc>January 27, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">February 6, 2020</results_first_posted>
  <last_update_submitted>January 27, 2020</last_update_submitted>
  <last_update_submitted_qc>January 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 6, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PreTerm Birth</keyword>
  <keyword>HIV</keyword>
  <keyword>Vaginal Progesterone</keyword>
  <keyword>ART</keyword>
  <keyword>Adherence</keyword>
  <keyword>Feasibility</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Premature Birth</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Progesterone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 10, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/52/NCT02970552/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Vaginal Progesterone</title>
          <description>Daily self-administered vaginal progesterone&#xD;
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Daily self-administered indistinguishable placebo&#xD;
Placebo: Indistinguishable placebo vaginal suppository</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="70"/>
                <participants group_id="P2" count="70"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="67"/>
                <participants group_id="P2" count="67"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Vaginal Progesterone</title>
          <description>Daily self-administered vaginal progesterone&#xD;
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Daily self-administered indistinguishable placebo&#xD;
Placebo: Indistinguishable placebo vaginal suppository</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="70"/>
            <count group_id="B2" value="70"/>
            <count group_id="B3" value="140"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="70"/>
                    <measurement group_id="B2" value="70"/>
                    <measurement group_id="B3" value="140"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="70"/>
                    <measurement group_id="B2" value="70"/>
                    <measurement group_id="B3" value="140"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="70"/>
                    <measurement group_id="B2" value="70"/>
                    <measurement group_id="B3" value="140"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Zambia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="70"/>
                    <measurement group_id="B2" value="70"/>
                    <measurement group_id="B3" value="140"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Adequate Adherence to Study Product</title>
        <description>Number of participants who achieved adequate adherence to study product, defined as proper self-administration of at least 80% of prescribed study product doses, as measured by a dye stain assay of returned applicators</description>
        <time_frame>Enrollment through 36th gestational week, an overall total of up to 17 weeks</time_frame>
        <population>Participants who returned for at least one follow-up study visit following enrollment</population>
        <group_list>
          <group group_id="O1">
            <title>Vaginal Progesterone</title>
            <description>Daily self-administered vaginal progesterone&#xD;
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Daily self-administered indistinguishable placebo&#xD;
Placebo: Indistinguishable placebo vaginal suppository</description>
          </group>
        </group_list>
        <measure>
          <title>Adequate Adherence to Study Product</title>
          <description>Number of participants who achieved adequate adherence to study product, defined as proper self-administration of at least 80% of prescribed study product doses, as measured by a dye stain assay of returned applicators</description>
          <population>Participants who returned for at least one follow-up study visit following enrollment</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="68"/>
                <count group_id="O2" value="69"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62"/>
                    <measurement group_id="O2" value="63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Acceptability of Use of Vaginal Progesterone (VP)</title>
        <description>Semi-structured interviews will be held with a random sample of participants who enroll and those who decline enrollment.</description>
        <time_frame>At enrollment (20-24 weeks gestation), at 28 weeks gestation, and at 36 weeks gestation</time_frame>
        <population>Activation was delayed by 6 months because of a protracted regulatory process. Resulting low resources limited investigators' ability to conduct interviews at all specified times or with decliners. Investigators did conduct a single interview with a sample of participants late in pregnancy or postpartum; these data are captured in outcomes #3 and 4</population>
        <group_list>
          <group group_id="O1">
            <title>Vaginal Progesterone</title>
            <description>Daily self-administered vaginal progesterone&#xD;
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Daily self-administered indistinguishable placebo&#xD;
Placebo: Indistinguishable placebo vaginal suppository</description>
          </group>
        </group_list>
        <measure>
          <title>Acceptability of Use of Vaginal Progesterone (VP)</title>
          <description>Semi-structured interviews will be held with a random sample of participants who enroll and those who decline enrollment.</description>
          <population>Activation was delayed by 6 months because of a protracted regulatory process. Resulting low resources limited investigators' ability to conduct interviews at all specified times or with decliners. Investigators did conduct a single interview with a sample of participants late in pregnancy or postpartum; these data are captured in outcomes #3 and 4</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Reported Barriers and Facilitators to Adherence to Study Product, Returning Used Applicators, and Retention in the Study</title>
        <description>Number of participants reporting barriers and facilitators to study product adherence, returning used applicators, and retention in the study during a semi-structured interview. Participants were selected for an interview based on their overall adherence rates, including those with excellent adherence throughout the study and those with lower adherence rates early or late in their participation. A trained female staff member conducted each 30-minute interview using an interview guide. Interviews were audiotaped, transcribed, and translated into English as necessary.</description>
        <time_frame>Late in pregnancy or postpartum</time_frame>
        <population>A sample of enrolled participants selected to participate in a semi-structured interview. Investigators included 30 trial participants based on expectations regarding saturation of qualitative themes.</population>
        <group_list>
          <group group_id="O1">
            <title>Vaginal Progesterone</title>
            <description>Daily self-administered vaginal progesterone Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Daily self-administered indistinguishable placebo Placebo: Indistinguishable placebo vaginal suppository</description>
          </group>
        </group_list>
        <measure>
          <title>Reported Barriers and Facilitators to Adherence to Study Product, Returning Used Applicators, and Retention in the Study</title>
          <description>Number of participants reporting barriers and facilitators to study product adherence, returning used applicators, and retention in the study during a semi-structured interview. Participants were selected for an interview based on their overall adherence rates, including those with excellent adherence throughout the study and those with lower adherence rates early or late in their participation. A trained female staff member conducted each 30-minute interview using an interview guide. Interviews were audiotaped, transcribed, and translated into English as necessary.</description>
          <population>A sample of enrolled participants selected to participate in a semi-structured interview. Investigators included 30 trial participants based on expectations regarding saturation of qualitative themes.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Reported any barriers to medication use</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Discontinued med due to challenges or discomfort</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Reported any facilitators to medication use</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Reported barrier to returning used applicators</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Reported barriers to returning for study visits</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Reported positive experience with study clinic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Summary of Reported Knowledge, Attitudes, and Practices Related to HIV, Antiretroviral Therapy (ART), Risk of Preterm Birth, and Participation in Placebo Controlled Randomized Clinical Trials (RCTs)</title>
        <description>Number of participants reporting attitudes and practices related to participation in placebo controlled RCTs during a semi-structured interview. Participants were selected for an interview based on their overall adherence rates, including those with excellent adherence throughout the study and those with lower adherence rates early or late in their participation. A trained female staff member conducted each 30-minute interview using an interview guide. Participants were asked about their attitudes toward participation in the study and research in general as HIV-infected women taking ART and at risk of preterm birth, but they were not specifically asked about their underlying knowledge of these conditions. Interviews were audio-taped, transcribed, and translated into English as necessary.</description>
        <time_frame>Late in pregnancy or postpartum</time_frame>
        <population>A sample of enrolled participants selected to participate in a semi-structured interview. Investigators included 30 trial participants based on expectations regarding saturation of qualitative themes.</population>
        <group_list>
          <group group_id="O1">
            <title>Vaginal Progesterone</title>
            <description>Daily self-administered vaginal progesterone Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Daily self-administered indistinguishable placebo Placebo: Indistinguishable placebo vaginal suppository</description>
          </group>
        </group_list>
        <measure>
          <title>Summary of Reported Knowledge, Attitudes, and Practices Related to HIV, Antiretroviral Therapy (ART), Risk of Preterm Birth, and Participation in Placebo Controlled Randomized Clinical Trials (RCTs)</title>
          <description>Number of participants reporting attitudes and practices related to participation in placebo controlled RCTs during a semi-structured interview. Participants were selected for an interview based on their overall adherence rates, including those with excellent adherence throughout the study and those with lower adherence rates early or late in their participation. A trained female staff member conducted each 30-minute interview using an interview guide. Participants were asked about their attitudes toward participation in the study and research in general as HIV-infected women taking ART and at risk of preterm birth, but they were not specifically asked about their underlying knowledge of these conditions. Interviews were audio-taped, transcribed, and translated into English as necessary.</description>
          <population>A sample of enrolled participants selected to participate in a semi-structured interview. Investigators included 30 trial participants based on expectations regarding saturation of qualitative themes.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Belief that being in the study prevented PTB</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Belief that women might refuse a placebo RCT</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Disclosed study participation to others</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Acceptability of a Vaginal Medication to Prevent Preterm Birth</title>
        <description>Number of participants reporting specific attitudes about medications for the prevention of preterm birth (PTB), including acceptability of daily vaginal administration as measured on the Exit Satisfaction Survey using a Likert scale of five possible options ranging from strongly agree to strongly disagree. The form included a range of facial illustrations to facilitate comprehension of the answer choices, particularly for illiterate participants.</description>
        <time_frame>Visit 9.0 (36 weeks of gestation)</time_frame>
        <population>131 randomized participants who completed an exit satisfaction survey</population>
        <group_list>
          <group group_id="O1">
            <title>Vaginal Progesterone</title>
            <description>Daily self-administered vaginal progesterone&#xD;
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Daily self-administered indistinguishable placebo&#xD;
Placebo: Indistinguishable placebo vaginal suppository</description>
          </group>
        </group_list>
        <measure>
          <title>Acceptability of a Vaginal Medication to Prevent Preterm Birth</title>
          <description>Number of participants reporting specific attitudes about medications for the prevention of preterm birth (PTB), including acceptability of daily vaginal administration as measured on the Exit Satisfaction Survey using a Likert scale of five possible options ranging from strongly agree to strongly disagree. The form included a range of facial illustrations to facilitate comprehension of the answer choices, particularly for illiterate participants.</description>
          <population>131 randomized participants who completed an exit satisfaction survey</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="67"/>
                <count group_id="O2" value="64"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Happy that I took part in the study</title>
              <category_list>
                <category>
                  <title>Strongly disagree</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Disagree</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Neutral</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Agree</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Strongly agree</title>
                  <measurement_list>
                    <measurement group_id="O1" value="66"/>
                    <measurement group_id="O2" value="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Did not mind taking daily vaginal medication</title>
              <category_list>
                <category>
                  <title>Strongly disagree</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Disagree</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Neutral</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Agree</title>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Strongly agree</title>
                  <measurement_list>
                    <measurement group_id="O1" value="58"/>
                    <measurement group_id="O2" value="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Would choose daily vag med over wkly injection</title>
              <category_list>
                <category>
                  <title>Strongly disagree</title>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Disagree</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Neutral</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Agree</title>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Strongly agree</title>
                  <measurement_list>
                    <measurement group_id="O1" value="43"/>
                    <measurement group_id="O2" value="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other women would like to take med to stop PTB</title>
              <category_list>
                <category>
                  <title>Strongly disagree</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Disagree</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Neutral</title>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Agree</title>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Strongly agree</title>
                  <measurement_list>
                    <measurement group_id="O1" value="40"/>
                    <measurement group_id="O2" value="44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Reported Barriers to Adherence to Study Product</title>
        <description>Number of participants reporting challenges with taking the study medication as measured on the Exit Satisfaction Survey. The survey was administered by a study nurse who asked each participant what was the hardest part about taking the medication and presented all possible answer choices. Participant were asked to select only one answer.</description>
        <time_frame>Visit 9.0 (36 weeks of gestation)</time_frame>
        <population>131 randomized participants who completed an exit satisfaction survey</population>
        <group_list>
          <group group_id="O1">
            <title>Vaginal Progesterone</title>
            <description>Daily self-administered vaginal progesterone&#xD;
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Daily self-administered indistinguishable placebo&#xD;
Placebo: Indistinguishable placebo vaginal suppository</description>
          </group>
        </group_list>
        <measure>
          <title>Reported Barriers to Adherence to Study Product</title>
          <description>Number of participants reporting challenges with taking the study medication as measured on the Exit Satisfaction Survey. The survey was administered by a study nurse who asked each participant what was the hardest part about taking the medication and presented all possible answer choices. Participant were asked to select only one answer.</description>
          <population>131 randomized participants who completed an exit satisfaction survey</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="67"/>
                <count group_id="O2" value="64"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Remembering to take it</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Didn't like using the product</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Obtaining refills at clinic</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Disclosing participation to partner or family</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Inserting the medication</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Nothing was hard about taking the medication</title>
                  <measurement_list>
                    <measurement group_id="O1" value="66"/>
                    <measurement group_id="O2" value="62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Sensitivity, Specificity, and Predictive Value of Dose Diaries</title>
        <description>Comparison of self-reported adherence rates (Dose Diary/DD) and use of returned applicators measured by dye stain assay (DSA)</description>
        <time_frame>Enrollment through 36th gestational week, an overall total of up to 17 weeks</time_frame>
        <population>Dose diaries completed by randomized participants returned at each follow-up visit, reported among participants who returned for at least 1 visit. Outcome assessed the reliability of dose diaries against DSA gold standard regardless of study arm to measure feasibility for future use. Estimates are presented in aggregate per original analysis plan.</population>
        <group_list>
          <group group_id="O1">
            <title>Daily Dose Diaries</title>
            <description>Dose diaries completed by randomized participants returned at each follow-up visit</description>
          </group>
        </group_list>
        <measure>
          <title>Sensitivity, Specificity, and Predictive Value of Dose Diaries</title>
          <description>Comparison of self-reported adherence rates (Dose Diary/DD) and use of returned applicators measured by dye stain assay (DSA)</description>
          <population>Dose diaries completed by randomized participants returned at each follow-up visit, reported among participants who returned for at least 1 visit. Outcome assessed the reliability of dose diaries against DSA gold standard regardless of study arm to measure feasibility for future use. Estimates are presented in aggregate per original analysis plan.</population>
          <units>Proportion of ppts correctly identified</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <units_analyzed>Daily dose diaries</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="137"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Daily dose diaries</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12256"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Sensitivity Pr(DD+/DSA+)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.999" lower_limit="0.999" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Specificity Pr(DD-/DSA-)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.571" lower_limit="0.521" upper_limit="0.619"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Positive Predictive Value Pr(DSA+/DD+)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.985" lower_limit="0.983" upper_limit="0.987"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Negative Predictive Value Pr(DSA-/DD-)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.975" lower_limit="0.946" upper_limit="0.991"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Enrollment of Eligible Participants</title>
        <description>Number of eligible participants who enrolled in the study</description>
        <time_frame>Screening through Enrollment</time_frame>
        <population>Women with a completed ultrasound who were eligible for study screening procedures</population>
        <group_list>
          <group group_id="O1">
            <title>Women Eligible for Screening</title>
            <description>Women eligible for study screening</description>
          </group>
        </group_list>
        <measure>
          <title>Enrollment of Eligible Participants</title>
          <description>Number of eligible participants who enrolled in the study</description>
          <population>Women with a completed ultrasound who were eligible for study screening procedures</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="208"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Successfully Screened</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="154"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Randomized</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="140"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ascertainment of Date of Delivery and Infant Vital Status</title>
        <description>Number of women for whom date of delivery and infant vital status at birth was ascertained</description>
        <time_frame>Visit 10.0 (Delivery)</time_frame>
        <population>All enrolled participants</population>
        <group_list>
          <group group_id="O1">
            <title>Vaginal Progesterone</title>
            <description>Daily self-administered vaginal progesterone&#xD;
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Daily self-administered indistinguishable placebo&#xD;
Placebo: Indistinguishable placebo vaginal suppository</description>
          </group>
        </group_list>
        <measure>
          <title>Ascertainment of Date of Delivery and Infant Vital Status</title>
          <description>Number of women for whom date of delivery and infant vital status at birth was ascertained</description>
          <population>All enrolled participants</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="70"/>
                <count group_id="O2" value="70"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67"/>
                    <measurement group_id="O2" value="67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Preliminary Efficacy</title>
        <description>Number of participants delivering before 34 and 37 completed weeks of gestation, grouped based on whether the participant went into labor spontaneously or was induced by a provider</description>
        <time_frame>Visit 10.0 (Delivery)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vaginal Progesterone</title>
            <description>Daily self-administered vaginal progesterone&#xD;
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Daily self-administered indistinguishable placebo&#xD;
Placebo: Indistinguishable placebo vaginal suppository</description>
          </group>
        </group_list>
        <measure>
          <title>Preliminary Efficacy</title>
          <description>Number of participants delivering before 34 and 37 completed weeks of gestation, grouped based on whether the participant went into labor spontaneously or was induced by a provider</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="67"/>
                <count group_id="O2" value="67"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Preterm birth &lt;37 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Spontaneous preterm birth &lt;37 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Preterm birth &lt;34 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Spontaneous preterm birth &lt;34 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Birth Weight</title>
        <description>Number of participants with neonates weighing less than 2500 grams at birth</description>
        <time_frame>Visit 10.0 (Delivery)</time_frame>
        <population>Randomized participants with birth weight data ascertained</population>
        <group_list>
          <group group_id="O1">
            <title>Vaginal Progesterone</title>
            <description>Daily self-administered vaginal progesterone&#xD;
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Daily self-administered indistinguishable placebo&#xD;
Placebo: Indistinguishable placebo vaginal suppository</description>
          </group>
        </group_list>
        <measure>
          <title>Birth Weight</title>
          <description>Number of participants with neonates weighing less than 2500 grams at birth</description>
          <population>Randomized participants with birth weight data ascertained</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="64"/>
                <count group_id="O2" value="64"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Stillbirth</title>
        <description>Number of participants who experienced a stillbirth</description>
        <time_frame>Visit 10.0 (Delivery)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vaginal Progesterone</title>
            <description>Daily self-administered vaginal progesterone&#xD;
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Daily self-administered indistinguishable placebo&#xD;
Placebo: Indistinguishable placebo vaginal suppository</description>
          </group>
        </group_list>
        <measure>
          <title>Stillbirth</title>
          <description>Number of participants who experienced a stillbirth</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="67"/>
                <count group_id="O2" value="67"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Adverse Events</title>
        <description>Number of women experiencing a serious adverse event or event that resulted in study product discontinuation</description>
        <time_frame>Enrollment through Visit 10.0 (Delivery)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vaginal Progesterone</title>
            <description>Daily self-administered vaginal progesterone&#xD;
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Daily self-administered indistinguishable placebo&#xD;
Placebo: Indistinguishable placebo vaginal suppository</description>
          </group>
        </group_list>
        <measure>
          <title>Adverse Events</title>
          <description>Number of women experiencing a serious adverse event or event that resulted in study product discontinuation</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="70"/>
                <count group_id="O2" value="70"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pre-eclampsia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stillbirth</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the time of enrollment through delivery, a total of approximately 16-20 weeks.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Vaginal Progesterone</title>
          <description>Daily self-administered vaginal progesterone&#xD;
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Daily self-administered indistinguishable placebo&#xD;
Placebo: Indistinguishable placebo vaginal suppository</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="70"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Pregnancy, puerperium and perinatal conditions</title>
            <event_list>
              <event>
                <sub_title>Stillbirth</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="70"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Pre-eclampsia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="34" subjects_at_risk="70"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea/Vomiting</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="70"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="15" subjects_affected="15" subjects_at_risk="70"/>
                <counts group_id="E2" events="10" subjects_affected="10" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Lower Abdominal Pain</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="70"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Vaginal Itching/Burning</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="70"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Joan Price, MD, MPH</name_or_title>
      <organization>University of North Carolina at Chapel Hill</organization>
      <phone>919-962-4717</phone>
      <email>joni@email.unc.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02970552
org study id: 16-2174
secondary id: 1R21HD090987-01
secondary id: Z 31606
nct id: NCT02970552
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
More than 1.5 million HIV-infected women become pregnant each year. Approximately half have
      access to antiretroviral therapy (ART), but all are at increased risk of preterm birth (PTB).
      Vaginal progesterone (VP) is a promising and cost-effective intervention to prevent PTB that
      should be studied in this high-risk population. This pilot study will provide critical
      insight into the feasibility of a phase III trial by determining whether women are willing to
      participate, to adhere to study drug, and to complete follow-up.
This will be a mixed method study to evaluate the feasibility and acceptability of a trial of
      VP to prevent PTB among HIV-infected Zambian women. To assess the feasibility of a full-scale
      clinical trial, the investigators will implement a pilot two-arm, double-masked,
      placebo-controlled trial of VP among HIV-infected women in antenatal care in Lusaka, Zambia.
      Participants will be randomly assigned to either daily self-administered VP or
      indistinguishable placebo prior to 24 weeks gestational age. In this pilot study, the
      investigators will be able to estimate study uptake, adherence to study product and protocol,
      and study retention. To assess the acceptability of a trial to test VP among HIV-infected
      women in Zambia, the investigators will employ a qualitative approach of longitudinal
      semi-structured interviews among women agreeing to trial participation and one-time
      semi-structured interviews (SSIs) among those who decline to participate.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Triple (Participant, Care Provider, Investigator)
measure: Adequate Adherence to Study Product
time frame: Enrollment through 36th gestational week, an overall total of up to 17 weeks
description: Number of participants who achieved adequate adherence to study product, defined as proper self-administration of at least 80% of prescribed study product doses, as measured by a dye stain assay of returned applicators
measure: Acceptability of Use of Vaginal Progesterone (VP)
time frame: At enrollment (20-24 weeks gestation), at 28 weeks gestation, and at 36 weeks gestation
description: Semi-structured interviews will be held with a random sample of participants who enroll and those who decline enrollment.
measure: Reported Barriers and Facilitators to Adherence to Study Product, Returning Used Applicators, and Retention in the Study
time frame: Late in pregnancy or postpartum
description: Number of participants reporting barriers and facilitators to study product adherence, returning used applicators, and retention in the study during a semi-structured interview. Participants were selected for an interview based on their overall adherence rates, including those with excellent adherence throughout the study and those with lower adherence rates early or late in their participation. A trained female staff member conducted each 30-minute interview using an interview guide. Interviews were audiotaped, transcribed, and translated into English as necessary.
measure: Summary of Reported Knowledge, Attitudes, and Practices Related to HIV, Antiretroviral Therapy (ART), Risk of Preterm Birth, and Participation in Placebo Controlled Randomized Clinical Trials (RCTs)
time frame: Late in pregnancy or postpartum
description: Number of participants reporting attitudes and practices related to participation in placebo controlled RCTs during a semi-structured interview. Participants were selected for an interview based on their overall adherence rates, including those with excellent adherence throughout the study and those with lower adherence rates early or late in their participation. A trained female staff member conducted each 30-minute interview using an interview guide. Participants were asked about their attitudes toward participation in the study and research in general as HIV-infected women taking ART and at risk of preterm birth, but they were not specifically asked about their underlying knowledge of these conditions. Interviews were audio-taped, transcribed, and translated into English as necessary.
measure: Acceptability of a Vaginal Medication to Prevent Preterm Birth
time frame: Visit 9.0 (36 weeks of gestation)
description: Number of participants reporting specific attitudes about medications for the prevention of preterm birth (PTB), including acceptability of daily vaginal administration as measured on the Exit Satisfaction Survey using a Likert scale of five possible options ranging from strongly agree to strongly disagree. The form included a range of facial illustrations to facilitate comprehension of the answer choices, particularly for illiterate participants.
measure: Reported Barriers to Adherence to Study Product
time frame: Visit 9.0 (36 weeks of gestation)
description: Number of participants reporting challenges with taking the study medication as measured on the Exit Satisfaction Survey. The survey was administered by a study nurse who asked each participant what was the hardest part about taking the medication and presented all possible answer choices. Participant were asked to select only one answer.
measure: Sensitivity, Specificity, and Predictive Value of Dose Diaries
time frame: Enrollment through 36th gestational week, an overall total of up to 17 weeks
description: Comparison of self-reported adherence rates (Dose Diary/DD) and use of returned applicators measured by dye stain assay (DSA)
measure: Enrollment of Eligible Participants
time frame: Screening through Enrollment
description: Number of eligible participants who enrolled in the study
measure: Ascertainment of Date of Delivery and Infant Vital Status
time frame: Visit 10.0 (Delivery)
description: Number of women for whom date of delivery and infant vital status at birth was ascertained
measure: Preliminary Efficacy
time frame: Visit 10.0 (Delivery)
description: Number of participants delivering before 34 and 37 completed weeks of gestation, grouped based on whether the participant went into labor spontaneously or was induced by a provider
measure: Birth Weight
time frame: Visit 10.0 (Delivery)
description: Number of participants with neonates weighing less than 2500 grams at birth
measure: Stillbirth
time frame: Visit 10.0 (Delivery)
description: Number of participants who experienced a stillbirth
measure: Adverse Events
time frame: Enrollment through Visit 10.0 (Delivery)
description: Number of women experiencing a serious adverse event or event that resulted in study product discontinuation
arm group label: Vaginal Progesterone
arm group type: Active Comparator
description: Daily self-administered vaginal progesterone
arm group label: Placebo
arm group type: Placebo Comparator
description: Daily self-administered indistinguishable placebo
intervention type: Drug
intervention name: Vaginal Progesterone
description: 200 mg micronized vaginal progesterone suppository
arm group label: Vaginal Progesterone
intervention type: Drug
intervention name: Placebo
description: Indistinguishable placebo vaginal suppository
arm group label: Placebo
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jeffrey Stringer, MD
role: Principal Investigator
affiliation: University of North Carolina, Chapel Hill
facility: 
country: Zambia
responsible party type: Sponsor
mesh term: Premature Birth
mesh term: Progesterone
sharing ipd: Undecided
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 