<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/NCT02225353</url>
  </required_header>
  <id_info>
    <org_study_id>EC12012/10IEI-9339</org_study_id>
    <nct_id>NCT02225353</nct_id>
  </id_info>
  <brief_title>Efficacy Study of a Cervical Pessary Containing Progesterone for the Prevention of Preterm Delivery</brief_title>
  <acronym>PCP002</acronym>
  <official_title>A Randomized, Open-Label, Controlled, Multi-Center Study on the Efficacy of a Sustained Release Progesterone Cerclage Cervical Pessary at Doses of 6.3 g or 7.7 g for the Prevention of Preterm Birth and a Maximum Duration of 20 Weeks.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Grünenthal GmbH</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Laboratorios Andromaco S.A.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Grünenthal GmbH</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Assess the efficacy of 2 Cervical Pessaries containing 6.3 g and 7.7 g micronized&#xD;
      progesterone for the prevention of preterm delivery, established through spontaneous birth&#xD;
      before gestation weeks 32 (31 weeks and 6 days) and 34 (33 weeks and 6 days), when the&#xD;
      pessary is inserted during weeks 16th and 24th and removed at 36 weeks and 6 days in pregnant&#xD;
      women at high risk of premature birth.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Participant selection will be performed by screening the general population of pregnant women&#xD;
      with single fetus monitored by the Hospital Healthcare Network, to investigate by serial&#xD;
      transvaginal ultrasound performed between gestation weeks 16 (0 day to 7 days) and 24 (0 day&#xD;
      to 7 days) those patients who have a cervical length between 10 mm and 25 mm, and/or women&#xD;
      with a single fetus and cervical length ≥10 mm presenting one or more of the following risk&#xD;
      factors:&#xD;
&#xD;
        1. preterm birth prior to 35 (34 weeks and 6 days) weeks of gestation;&#xD;
&#xD;
        2. premature rupture of membranes prior to 35 (34 and 6 days) weeks of gestation.&#xD;
&#xD;
      After insertion of the pessary or beginning of the administration with vaginal progesterone&#xD;
      capsules and until 28 weeks of gestation, participants in the 3 treatment groups will be&#xD;
      monitored every 4 weeks at the most or more often, if the site has established so as a&#xD;
      control standard. After 28 weeks, patients should be monitored every 2 weeks.&#xD;
&#xD;
      The proportions of spontaneous preterm delivery before gestation weeks 32 and 34 will be&#xD;
      compared between the control group and the 2 groups with the pessaries containing different&#xD;
      doses of progesterone.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2, 2013</start_date>
  <completion_date type="Actual">March 13, 2017</completion_date>
  <primary_completion_date type="Actual">March 13, 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants Not Giving Birth Before Week 32 and Week 34 of Gestation</measure>
    <time_frame>Up to 36 weeks of gestational age</time_frame>
    <description>To assess the efficacy of Cerclage Pessaries containing 6.3 g and 7.7 g micronized progesterone for the prevention of preterm delivery, established through spontaneous parturition before gestation weeks 32 (31 weeks and 6 days) and 34 (33 weeks and 6 days), when the pessary is inserted between weeks 16 and 24 and removed at 36 weeks and 6 days in pregnant women at high risk of premature delivery.&#xD;
For the purpose of this analysis, pregnancies were no longer considered as high risk for the event if delivery occurred at week 34 of gestation and beyond. Gestational age was determined by the last menstruation date and were confirmed by measurement of the craniocaudal length obtained in the first trimester ultrasound, or by measurement of the cephalic circumference in the second trimester ultrasound predominating the actual date of the last menstrual period.&#xD;
The number of participants not giving birth before 32 weeks and 34 weeks are reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Premature Rupture of Membranes</measure>
    <time_frame>Up to 36 weeks of gestational age</time_frame>
    <description>A participant with premature rupture of membrane typically recalls a sudden gush of fluid loss from the vagina, or steady loss of small amounts of fluid. Participants who reported vaginal discharge were examined by a physician.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anatomical Feature: Length of the Uterine Cervix</measure>
    <time_frame>Up to 36 weeks of gestational age. Results are reported for all assessments from baseline through final visit, for a total of 8 visits, and for up to 36 weeks of gestational age.</time_frame>
    <description>During the pregnancy the length of the uterine cervix will be assessed. The rational is that premature birth is associated with uterine cervix shortening. The length of the cervix was determined using ultrasound examination. A positive change from baseline indicates a positive development, i.e. less likely to result in a preterm birth. The comparison between premature an normal birth initially planned by the protocol was not analyzed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anatomical Feature: Position of the Uterine Cervix</measure>
    <time_frame>Up to 36 weeks of gestational age. Results are reported for all assessments from baseline through final visit, for a total of 8 visits, and for up to 36 weeks of gestational age.</time_frame>
    <description>During the pregnancy the position of the uterine cervix will be assessed. The rational being that premature birth is associated with uterine cervix positioning. The position of the cervix was determined using transvaginal ultrasound examination. In the change from baseline visit a positive value change indicated that the investigator believed that the position of the cervix changed in a positive manner to facilitate a term birth. The comparison between premature an normal birth initially planned by the protocol was not analyzed. The results reported are the degrees of the cervix position relative to the longitudinal axis of the uterus.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acceptability and Tolerance of Use of the Cerclage Pessary</measure>
    <time_frame>Up to 36 weeks of gestational age</time_frame>
    <description>A questionnaire was planned to be used to compare acceptability and tolerance in the insertion, during pregnancy and during the extraction of Cerclage Pessary.&#xD;
Data from this questionnaire was not collected.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Adverse Events Related With the Use of Treatment</measure>
    <time_frame>Up to 36 weeks of gestational age</time_frame>
    <description>The number of adverse events reported were analyzed as being related with the treatment as well as for unexpectedness.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">271</enrollment>
  <condition>Preterm Birth</condition>
  <arm_group>
    <arm_group_label>Progesterone Cervical Pessary 6.3 g</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>90 pregnant women with Progesterone Cervical Pessary</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Progesterone Cervical Pessary 7.7 g</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>90 pregnant women with Progesterone Cervical Pessary</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Progesterone 200 mg vaginal capsules</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>90 pregnant women using Progesterone 200 mg vaginal capsules daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Progesterone Cervical Pessary 6.3 g</intervention_name>
    <description>Progesterone Cervical Pessary low dose</description>
    <arm_group_label>Progesterone Cervical Pessary 6.3 g</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Progesterone 200 mg vaginal capsules</intervention_name>
    <description>Progesterone 200 mg vaginal capsules daily</description>
    <arm_group_label>Progesterone 200 mg vaginal capsules</arm_group_label>
    <other_name>Hormoral (Trade Mark) Capsules</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Progesterone Cervical Pessary 7.7 g</intervention_name>
    <description>Progesterone Cervical Pessary high dose</description>
    <arm_group_label>Progesterone Cervical Pessary 7.7 g</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women with a single pregnancy and a cervical length of 10 mm - 25 mm between 16 and 24&#xD;
             weeks of gestation, without any previous factors.&#xD;
&#xD;
          -  Women with a single pregnancy with 10 mm or more cervical length between 16 and 24&#xD;
             weeks of gestation, and pre-existing risk factors risk factors for preterm birth:&#xD;
&#xD;
          -  Previous preterm birth before week 35.&#xD;
&#xD;
          -  Previous rupture of membranes before week 35&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancies with:&#xD;
&#xD;
               -  Major fetal abnormalities, such as lethal malformations or malformations&#xD;
                  requiring pre- or post-natal surgery; and fetal death before inclusion into the&#xD;
                  study.&#xD;
&#xD;
               -  History of rupture of membranes or prophylactic cerclage before study entry.&#xD;
&#xD;
          -  Cervical or vaginal injuries prior to insertion of the pessary (e.g., cervical erosion&#xD;
             secondary to trauma, infection, or carcinoma; vesicovaginal or rectovaginal fistulas).&#xD;
&#xD;
          -  Unconscious, severely ill or mentally disabled patients, or under 16 years of age.&#xD;
&#xD;
          -  Patients for whom use of progesterone is contraindicated.&#xD;
&#xD;
          -  Patients with history of thrombosis.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Grünenthal Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Grünenthal GmbH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Universidad de Chile, Hospital Barros Luco</name>
      <address>
        <city>Santiago</city>
        <zip>7501257</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complejo Asistencial Dr. Sótero del Río (CASR)</name>
      <address>
        <city>Santiago</city>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Unidad de Alto Riesgo Obstétrico y Medicina Perinatal y en el Centro Perinatal Oriente (CERPO), Hospital Santiago Oriente, Dr. Luis Tisné Brousse</name>
      <address>
        <city>Santiago</city>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universidad de Chile, Hospital Clínico San Borja Arriarán</name>
      <address>
        <city>Santiago</city>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Chile</country>
  </location_countries>
  <reference>
    <citation>Dodd JM, Crowther CA, Cincotta R, Flenady V, Robinson JS. Progesterone supplementation for preventing preterm birth: a systematic review and meta-analysis. Acta Obstet Gynecol Scand. 2005 Jun;84(6):526-33. doi: 10.1111/j.0001-6349.2005.00835.x.</citation>
    <PMID>15901258</PMID>
  </reference>
  <reference>
    <citation>Berghella V. Novel developments on cervical length screening and progesterone for preventing preterm birth. BJOG. 2009 Jan;116(2):182-7. doi: 10.1111/j.1471-0528.2008.02008.x.</citation>
    <PMID>19076950</PMID>
  </reference>
  <reference>
    <citation>Jayasooriya GS, Lamont RF. The use of progesterone and other progestational agents to prevent spontaneous preterm labour and preterm birth. Expert Opin Pharmacother. 2009 Apr;10(6):1007-16. doi: 10.1517/14656560902851403.</citation>
    <PMID>19351272</PMID>
  </reference>
  <reference>
    <citation>Newcomer J. Pessaries for the treatment of incompetent cervix and premature delivery. Obstet Gynecol Surv. 2000 Jul;55(7):443-8. doi: 10.1097/00006254-200007000-00023.</citation>
    <PMID>10885649</PMID>
  </reference>
  <reference>
    <citation>Arabin B, Halbesma JR, Vork F, Hubener M, van Eyck J. Is treatment with vaginal pessaries an option in patients with a sonographically detected short cervix? J Perinat Med. 2003;31(2):122-33. doi: 10.1515/JPM.2003.017.</citation>
    <PMID>12747228</PMID>
  </reference>
  <reference>
    <citation>Goya M, Pratcorona L, Merced C, Rodo C, Valle L, Romero A, Juan M, Rodriguez A, Munoz B, Santacruz B, Bello-Munoz JC, Llurba E, Higueras T, Cabero L, Carreras E; Pesario Cervical para Evitar Prematuridad (PECEP) Trial Group. Cervical pessary in pregnant women with a short cervix (PECEP): an open-label randomised controlled trial. Lancet. 2012 May 12;379(9828):1800-6. doi: 10.1016/S0140-6736(12)60030-0. Epub 2012 Apr 3. Erratum In: Lancet. 2012 May 12;379(9828):1790.</citation>
    <PMID>22475493</PMID>
  </reference>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>August 4, 2014</study_first_submitted>
  <study_first_submitted_qc>August 24, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 26, 2014</study_first_posted>
  <results_first_submitted>March 5, 2018</results_first_submitted>
  <results_first_submitted_qc>October 20, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">October 23, 2018</results_first_posted>
  <last_update_submitted>October 20, 2018</last_update_submitted>
  <last_update_submitted_qc>October 20, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 23, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Preterm birth</keyword>
  <keyword>Short cervix</keyword>
  <keyword>Cervical Pessaries</keyword>
  <keyword>Progesterone</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>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>May 16, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/53/NCT02225353/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 12, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/53/NCT02225353/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The trial started on 02 Sep 2013 with the enrollment of the first participant and was completed on 13 Mar 2017 when the last participant completed the last follow-up examination according to the protocol. 271 participants signed and informed consent. All 271 were randomized and treated.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Progesterone Cervical Pessary (6.3 g)</title>
          <description>Cervical Pessary (PCP) with sustained release of progesterone. The PCP is inserted by investigator to participant at risk of preterm birth and remains installed with no further intervention except at the time of removal.</description>
        </group>
        <group group_id="P2">
          <title>Progesterone Cervical Pessary (7.7 g)</title>
          <description>Cervical Pessary (PCP) with sustained release of progesterone. The PCP is inserted by investigator to participant at risk of preterm birth and remains installed with no further intervention except at the time of removal.</description>
        </group>
        <group group_id="P3">
          <title>Progesterone 200 mg Vaginal Capsules</title>
          <description>Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily by participant.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="91"/>
                <participants group_id="P2" count="90"/>
                <participants group_id="P3" count="90"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="87"/>
                <participants group_id="P2" count="84"/>
                <participants group_id="P3" count="75"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="15"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="12"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Intent-to-treat.</population>
      <group_list>
        <group group_id="B1">
          <title>Progesterone Cervical Pessary (6.3 g)</title>
          <description>Cervical pessary (PCP) with sustained release of progesterone. The PCP is inserted by investigator to participant (at risk of preterm birth) and remains installed with no further intervention except at the time of removal.</description>
        </group>
        <group group_id="B2">
          <title>Progesterone Cervical Pessary (7.7 g)</title>
          <description>Cervical pessary (PCP) with sustained release of progesterone. The PCP is inserted by investigator to participant (at risk of preterm birth) and remains installed with no further intervention except at the time of removal.</description>
        </group>
        <group group_id="B3">
          <title>Progesterone 200 mg Vaginal Capsules</title>
          <description>Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily by participant.</description>
        </group>
        <group group_id="B4">
          <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="91"/>
            <count group_id="B2" value="90"/>
            <count group_id="B3" value="90"/>
            <count group_id="B4" value="271"/>
          </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 group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="91"/>
                    <measurement group_id="B2" value="90"/>
                    <measurement group_id="B3" value="90"/>
                    <measurement group_id="B4" value="271"/>
                  </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 group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27.57" spread="6.50"/>
                    <measurement group_id="B2" value="27.60" spread="6.20"/>
                    <measurement group_id="B3" value="28.18" spread="5.16"/>
                    <measurement group_id="B4" value="27.78" spread="5.97"/>
                  </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="91"/>
                    <measurement group_id="B2" value="90"/>
                    <measurement group_id="B3" value="90"/>
                    <measurement group_id="B4" value="271"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="NA">Male was an exclusion criterion</measurement>
                    <measurement group_id="B2" value="NA">Male was an exclusion criterion</measurement>
                    <measurement group_id="B3" value="NA">Male was an exclusion criterion</measurement>
                    <measurement group_id="B4" value="NA">Total not calculated because data are not available (NA) in one or more arms.</measurement>
                  </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 group_id="B4" 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 group_id="B4" 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 group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </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 group_id="B4" 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 group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="91"/>
                    <measurement group_id="B2" value="90"/>
                    <measurement group_id="B3" value="90"/>
                    <measurement group_id="B4" value="271"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Chile</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="91"/>
                    <measurement group_id="B2" value="90"/>
                    <measurement group_id="B3" value="90"/>
                    <measurement group_id="B4" value="271"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <units>meter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1.57" spread="0.06"/>
                    <measurement group_id="B2" value="1.58" spread="0.06"/>
                    <measurement group_id="B3" value="1.58" spread="0.05"/>
                    <measurement group_id="B4" value="1.58" spread="0.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>kilogram</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="66.65" spread="13.36"/>
                    <measurement group_id="B2" value="71.26" spread="14.06"/>
                    <measurement group_id="B3" value="70.62" spread="12.73"/>
                    <measurement group_id="B4" value="69.50" spread="13.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index (BMI)</title>
          <units>kilogram per square meter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27.03" spread="4.92"/>
                    <measurement group_id="B2" value="28.61" spread="5.45"/>
                    <measurement group_id="B3" value="28.23" spread="4.56"/>
                    <measurement group_id="B4" value="27.95" spread="5.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Medical History - Prior Preterm Birth</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="55"/>
                    <measurement group_id="B2" value="55"/>
                    <measurement group_id="B3" value="50"/>
                    <measurement group_id="B4" value="160"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Medical History - Prior Pregnancy Premature Rupture of Membrane</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="17"/>
                    <measurement group_id="B4" value="61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Not Giving Birth Before Week 32 and Week 34 of Gestation</title>
        <description>To assess the efficacy of Cerclage Pessaries containing 6.3 g and 7.7 g micronized progesterone for the prevention of preterm delivery, established through spontaneous parturition before gestation weeks 32 (31 weeks and 6 days) and 34 (33 weeks and 6 days), when the pessary is inserted between weeks 16 and 24 and removed at 36 weeks and 6 days in pregnant women at high risk of premature delivery.&#xD;
For the purpose of this analysis, pregnancies were no longer considered as high risk for the event if delivery occurred at week 34 of gestation and beyond. Gestational age was determined by the last menstruation date and were confirmed by measurement of the craniocaudal length obtained in the first trimester ultrasound, or by measurement of the cephalic circumference in the second trimester ultrasound predominating the actual date of the last menstrual period.&#xD;
The number of participants not giving birth before 32 weeks and 34 weeks are reported.</description>
        <time_frame>Up to 36 weeks of gestational age</time_frame>
        <population>271 participants comprised the Intention-to-treat analysis (ITT) population at baseline, 268 participants at gestation week 32, and 262 participants at gestation week 34.</population>
        <group_list>
          <group group_id="O1">
            <title>Progesterone Cervical Pessary (6.3 g)</title>
            <description>Cervical Pessary with sustained release of progesterone.Single placement and removal by investigator site.</description>
          </group>
          <group group_id="O2">
            <title>Progesterone Cervical Pessary (7.7 g)</title>
            <description>Cervical Pessary with sustained release of progesterone. Single placement and removal by investigator site.</description>
          </group>
          <group group_id="O3">
            <title>Progesterone 200 mg Vaginal Capsules</title>
            <description>Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily by participant.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Not Giving Birth Before Week 32 and Week 34 of Gestation</title>
          <description>To assess the efficacy of Cerclage Pessaries containing 6.3 g and 7.7 g micronized progesterone for the prevention of preterm delivery, established through spontaneous parturition before gestation weeks 32 (31 weeks and 6 days) and 34 (33 weeks and 6 days), when the pessary is inserted between weeks 16 and 24 and removed at 36 weeks and 6 days in pregnant women at high risk of premature delivery.&#xD;
For the purpose of this analysis, pregnancies were no longer considered as high risk for the event if delivery occurred at week 34 of gestation and beyond. Gestational age was determined by the last menstruation date and were confirmed by measurement of the craniocaudal length obtained in the first trimester ultrasound, or by measurement of the cephalic circumference in the second trimester ultrasound predominating the actual date of the last menstrual period.&#xD;
The number of participants not giving birth before 32 weeks and 34 weeks are reported.</description>
          <population>271 participants comprised the Intention-to-treat analysis (ITT) population at baseline, 268 participants at gestation week 32, and 262 participants at gestation week 34.</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="91"/>
                <count group_id="O2" value="90"/>
                <count group_id="O3" value="90"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>No birth before 32 weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="90"/>
                    <count group_id="O2" value="90"/>
                    <count group_id="O3" value="88"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="73"/>
                    <measurement group_id="O2" value="71"/>
                    <measurement group_id="O3" value="67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No birth before 34 weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="89"/>
                    <count group_id="O2" value="88"/>
                    <count group_id="O3" value="85"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="66"/>
                    <measurement group_id="O2" value="64"/>
                    <measurement group_id="O3" value="61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Premature Rupture of Membranes</title>
        <description>A participant with premature rupture of membrane typically recalls a sudden gush of fluid loss from the vagina, or steady loss of small amounts of fluid. Participants who reported vaginal discharge were examined by a physician.</description>
        <time_frame>Up to 36 weeks of gestational age</time_frame>
        <population>Intention-to-Treat Population</population>
        <group_list>
          <group group_id="O1">
            <title>Progesterone Cervical Pessary (6.3 g)</title>
            <description>Cervical Pessary with sustained release of progesterone.Single placement and removal by investigator site.</description>
          </group>
          <group group_id="O2">
            <title>Progesterone Cervical Pessary (7.7 g)</title>
            <description>Cervical Pessary with sustained release of progesterone. Single placement and removal by investigator site.</description>
          </group>
          <group group_id="O3">
            <title>Progesterone 200 mg Vaginal Capsules</title>
            <description>Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily by participant.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Premature Rupture of Membranes</title>
          <description>A participant with premature rupture of membrane typically recalls a sudden gush of fluid loss from the vagina, or steady loss of small amounts of fluid. Participants who reported vaginal discharge were examined by a physician.</description>
          <population>Intention-to-Treat Population</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="91"/>
                <count group_id="O2" value="90"/>
                <count group_id="O3" value="90"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Anatomical Feature: Length of the Uterine Cervix</title>
        <description>During the pregnancy the length of the uterine cervix will be assessed. The rational is that premature birth is associated with uterine cervix shortening. The length of the cervix was determined using ultrasound examination. A positive change from baseline indicates a positive development, i.e. less likely to result in a preterm birth. The comparison between premature an normal birth initially planned by the protocol was not analyzed.</description>
        <time_frame>Up to 36 weeks of gestational age. Results are reported for all assessments from baseline through final visit, for a total of 8 visits, and for up to 36 weeks of gestational age.</time_frame>
        <population>Intention-to-treat (ITT).</population>
        <group_list>
          <group group_id="O1">
            <title>Progesterone Cervical Pessary (6.3 g)</title>
            <description>Cervical Pessary with sustained release of progesterone. Single placement and removal by investigator site.</description>
          </group>
          <group group_id="O2">
            <title>Progesterone Cervical Pessary (7.7 g)</title>
            <description>Cervical Pessary with sustained release of progesterone. Single placement and removal by investigator site.</description>
          </group>
          <group group_id="O3">
            <title>Progesterone 200 mg Vaginal Capsules</title>
            <description>Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily by participant.</description>
          </group>
        </group_list>
        <measure>
          <title>Anatomical Feature: Length of the Uterine Cervix</title>
          <description>During the pregnancy the length of the uterine cervix will be assessed. The rational is that premature birth is associated with uterine cervix shortening. The length of the cervix was determined using ultrasound examination. A positive change from baseline indicates a positive development, i.e. less likely to result in a preterm birth. The comparison between premature an normal birth initially planned by the protocol was not analyzed.</description>
          <population>Intention-to-treat (ITT).</population>
          <units>millimeter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="91"/>
                <count group_id="O2" value="90"/>
                <count group_id="O3" value="90"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline Visit</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="91"/>
                    <count group_id="O2" value="89"/>
                    <count group_id="O3" value="89"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.69" spread="9.06"/>
                    <measurement group_id="O2" value="29.62" spread="8.66"/>
                    <measurement group_id="O3" value="28.44" spread="8.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="82"/>
                    <count group_id="O2" value="78"/>
                    <count group_id="O3" value="76"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.51" spread="8.30"/>
                    <measurement group_id="O2" value="30.34" spread="7.63"/>
                    <measurement group_id="O3" value="29.29" spread="10.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="74"/>
                    <count group_id="O2" value="75"/>
                    <count group_id="O3" value="69"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.54" spread="7.27"/>
                    <measurement group_id="O2" value="29.06" spread="7.65"/>
                    <measurement group_id="O3" value="30.76" spread="8.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="69"/>
                    <count group_id="O2" value="71"/>
                    <count group_id="O3" value="64"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.82" spread="7.12"/>
                    <measurement group_id="O2" value="27.60" spread="7.91"/>
                    <measurement group_id="O3" value="29.37" spread="8.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="61"/>
                    <count group_id="O2" value="67"/>
                    <count group_id="O3" value="62"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.53" spread="7.40"/>
                    <measurement group_id="O2" value="26.55" spread="7.81"/>
                    <measurement group_id="O3" value="28.63" spread="10.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                    <count group_id="O2" value="43"/>
                    <count group_id="O3" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.42" spread="7.62"/>
                    <measurement group_id="O2" value="27.28" spread="9.36"/>
                    <measurement group_id="O3" value="27.49" spread="8.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="28"/>
                    <count group_id="O2" value="24"/>
                    <count group_id="O3" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.43" spread="9.39"/>
                    <measurement group_id="O2" value="27.95" spread="8.85"/>
                    <measurement group_id="O3" value="28.83" spread="8.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Final Visit</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="49"/>
                    <count group_id="O2" value="47"/>
                    <count group_id="O3" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.98" spread="8.06"/>
                    <measurement group_id="O2" value="25.07" spread="7.49"/>
                    <measurement group_id="O3" value="23.64" spread="9.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Anatomical Feature: Position of the Uterine Cervix</title>
        <description>During the pregnancy the position of the uterine cervix will be assessed. The rational being that premature birth is associated with uterine cervix positioning. The position of the cervix was determined using transvaginal ultrasound examination. In the change from baseline visit a positive value change indicated that the investigator believed that the position of the cervix changed in a positive manner to facilitate a term birth. The comparison between premature an normal birth initially planned by the protocol was not analyzed. The results reported are the degrees of the cervix position relative to the longitudinal axis of the uterus.</description>
        <time_frame>Up to 36 weeks of gestational age. Results are reported for all assessments from baseline through final visit, for a total of 8 visits, and for up to 36 weeks of gestational age.</time_frame>
        <population>Intention-to-treat (ITT).</population>
        <group_list>
          <group group_id="O1">
            <title>Progesterone Cervical Pessary (6.3 g)</title>
            <description>Cervical Pessary with sustained release of progesterone. Single placement and removal by investigator site.</description>
          </group>
          <group group_id="O2">
            <title>Progesterone Cervical Pessary (7.7 g)</title>
            <description>Cervical Pessary with sustained release of progesterone. Single placement and removal by investigator site.</description>
          </group>
          <group group_id="O3">
            <title>Progesterone 200 mg Vaginal Capsules</title>
            <description>Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily by participant.</description>
          </group>
        </group_list>
        <measure>
          <title>Anatomical Feature: Position of the Uterine Cervix</title>
          <description>During the pregnancy the position of the uterine cervix will be assessed. The rational being that premature birth is associated with uterine cervix positioning. The position of the cervix was determined using transvaginal ultrasound examination. In the change from baseline visit a positive value change indicated that the investigator believed that the position of the cervix changed in a positive manner to facilitate a term birth. The comparison between premature an normal birth initially planned by the protocol was not analyzed. The results reported are the degrees of the cervix position relative to the longitudinal axis of the uterus.</description>
          <population>Intention-to-treat (ITT).</population>
          <units>degrees</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="91"/>
                <count group_id="O2" value="90"/>
                <count group_id="O3" value="90"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline Visit</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="54"/>
                    <count group_id="O2" value="58"/>
                    <count group_id="O3" value="40"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="114.54" spread="22.58"/>
                    <measurement group_id="O2" value="112.59" spread="22.48"/>
                    <measurement group_id="O3" value="112.85" spread="20.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="43"/>
                    <count group_id="O3" value="31"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="111.47" spread="23.33"/>
                    <measurement group_id="O2" value="115.02" spread="19.56"/>
                    <measurement group_id="O3" value="109.74" spread="23.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="40"/>
                    <count group_id="O2" value="39"/>
                    <count group_id="O3" value="32"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="110.81" spread="17.78"/>
                    <measurement group_id="O2" value="109.83" spread="25.65"/>
                    <measurement group_id="O3" value="115.36" spread="24.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                    <count group_id="O2" value="40"/>
                    <count group_id="O3" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="105.58" spread="21.35"/>
                    <measurement group_id="O2" value="117.61" spread="18.63"/>
                    <measurement group_id="O3" value="113.29" spread="26.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="31"/>
                    <count group_id="O2" value="32"/>
                    <count group_id="O3" value="25"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="108.99" spread="21.97"/>
                    <measurement group_id="O2" value="115.50" spread="19.15"/>
                    <measurement group_id="O3" value="113.26" spread="15.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="17"/>
                    <count group_id="O2" value="16"/>
                    <count group_id="O3" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="112.96" spread="17.41"/>
                    <measurement group_id="O2" value="114.50" spread="21.61"/>
                    <measurement group_id="O3" value="121.65" spread="15.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                    <count group_id="O2" value="14"/>
                    <count group_id="O3" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="118.93" spread="14.10"/>
                    <measurement group_id="O2" value="110.51" spread="20.94"/>
                    <measurement group_id="O3" value="124.37" spread="13.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Final Visit</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="29"/>
                    <count group_id="O2" value="26"/>
                    <count group_id="O3" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="104.30" spread="23.98"/>
                    <measurement group_id="O2" value="113.42" spread="24.76"/>
                    <measurement group_id="O3" value="115.44" spread="16.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Acceptability and Tolerance of Use of the Cerclage Pessary</title>
        <description>A questionnaire was planned to be used to compare acceptability and tolerance in the insertion, during pregnancy and during the extraction of Cerclage Pessary.&#xD;
Data from this questionnaire was not collected.</description>
        <time_frame>Up to 36 weeks of gestational age</time_frame>
        <population>No participants were analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>Progesterone Cervical Pessary (6.3 g)</title>
            <description>Cervical pessary (PCP) with sustained release of progesterone. The PCP is inserted by investigator to participant (at risk of preterm birth) and remains installed with no further intervention except at the time of removal.</description>
          </group>
          <group group_id="O2">
            <title>Progesterone Cervical Pessary (7.7 g)</title>
            <description>Cervical pessary (PCP) with sustained release of progesterone. The PCP is inserted by investigator to participant (at risk of preterm birth) and remains installed with no further intervention except at the time of removal.</description>
          </group>
          <group group_id="O3">
            <title>Progesterone 200 mg Vaginal Capsules</title>
            <description>Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily by participant.</description>
          </group>
        </group_list>
        <measure>
          <title>Acceptability and Tolerance of Use of the Cerclage Pessary</title>
          <description>A questionnaire was planned to be used to compare acceptability and tolerance in the insertion, during pregnancy and during the extraction of Cerclage Pessary.&#xD;
Data from this questionnaire was not collected.</description>
          <population>No participants were analyzed</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 group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Adverse Events Related With the Use of Treatment</title>
        <description>The number of adverse events reported were analyzed as being related with the treatment as well as for unexpectedness.</description>
        <time_frame>Up to 36 weeks of gestational age</time_frame>
        <population>Intention-to-treat (ITT)</population>
        <group_list>
          <group group_id="O1">
            <title>Progesterone Cervical Pessary (6.3 g)</title>
            <description>Cervical pessary (PCP) with sustained release of progesterone. The PCP is inserted by investigator to participant (at risk of preterm birth) and remains installed with no further intervention except at the time of removal.</description>
          </group>
          <group group_id="O2">
            <title>Progesterone Cervical Pessary (7.7 g)</title>
            <description>Cervical pessary (PCP) with sustained release of progesterone. The PCP is inserted by investigator to participant (at risk of preterm birth) and remains installed with no further intervention except at the time of removal.</description>
          </group>
          <group group_id="O3">
            <title>Progesterone 200 mg Vaginal Capsules</title>
            <description>Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily by participant.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Adverse Events Related With the Use of Treatment</title>
          <description>The number of adverse events reported were analyzed as being related with the treatment as well as for unexpectedness.</description>
          <population>Intention-to-treat (ITT)</population>
          <units>events</units>
          <param>Number</param>
          <units_analyzed>number of adverse events</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="91"/>
                <count group_id="O2" value="90"/>
                <count group_id="O3" value="90"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>number of adverse events</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="200"/>
                <count group_id="O2" value="248"/>
                <count group_id="O3" value="200"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AE related to use of treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31"/>
                    <measurement group_id="O2" value="22"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unexpected serious adverse events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks).</time_frame>
      <desc>Treatment emergent adverse events.</desc>
      <group_list>
        <group group_id="E1">
          <title>Progesterone Cervical Pessary 6.3 g</title>
          <description>91 pregnant women with Progesterone Cervical Pessary&#xD;
Progesterone Cervical Pessary: Progesterone Cervical Pessary: 6.3 g Progesterone Cervical Pessary: 7.7 g</description>
        </group>
        <group group_id="E2">
          <title>Progesterone Cervical Pessary 7.7 g</title>
          <description>90 pregnant women with Progesterone Cervical Pessary&#xD;
Progesterone Cervical Pessary: Progesterone Cervical Pessary: 6.3 g Progesterone Cervical Pessary: 7.7 g</description>
        </group>
        <group group_id="E3">
          <title>Progesterone 200 mg Vaginal Capsules</title>
          <description>90 pregnant women using Progesterone 200 mg vaginal capsules daily&#xD;
Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (17.0)</default_vocab>
        <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="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="36" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="35" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="33" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Congenital, familial and genetic disorders</title>
            <event_list>
              <event>
                <sub_title>Ventricular hypoplasia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Multiple congenital anomalies</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Cholestasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Breast abscess</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Asymptomatic bacteriuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Bacterial vaginosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Pyelonephritis acute</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Bacteriuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood Pressure Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetic Metabolic Decompensation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pelvic pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebral ventricle dilatation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Foetal cerebrovascular disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Pregnancy, puerperium and perinatal conditions</title>
            <event_list>
              <event>
                <sub_title>Cervical incompetence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Foetal death</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Foetal growth restriction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Oligohydramnios</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Preeclampsia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Premature rupture of membranes</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Threatened labour</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Gestational hypertension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Haemorrhage in pregnancy</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Polihidroamnios</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Umbilical cord abnormality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Premature labor</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Foetal hypokinesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>HELLP syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Uterine contractions during pregnancy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Drug use disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Hydronephrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Renal Colic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Shortened cervix</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="19" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Pelvic pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Vaginal erosion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Vaginal infection NOS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Coital bleeding</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Cervix haemorrhage uterine</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Uterine haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertensive crisis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (17.0)</default_vocab>
        <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="77" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="73" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="65" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Congenital, familial and genetic disorders</title>
            <event_list>
              <event>
                <sub_title>Congenital uterine anomaly</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Abdominal pain lower</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Dental caries</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Hyperchlorhydria</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Faecaloma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Duodenogastric reflux</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Cholestasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bacterial vaginosis</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Cervicitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Fungal infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Gastrenteritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Vaginal infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Vaginitis gardnerella</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Viral pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Vulvovaginal candidasis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Vulvovaginitis</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Tooth infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Gynaecological chlamydia infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Ureaplasma infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Mycoplasma infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Vulvovaginal mycotic infection</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Vaginitis chlamydial</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Arthropod bite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Thermal burn</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Tooth fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Amniocentesis abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Ultrasound uterus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Ultrasound uterus abnormal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Ureaplasma test positive</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Mycoplasma test positive</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Foetal renal imaging abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetic metabolic decompensation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Coccydynia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Pubic pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Vulvovaginal warts</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Carpal tunnel syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Facial paralysis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="12" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Tension headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Pregnancy, puerperium and perinatal conditions</title>
            <event_list>
              <event>
                <sub_title>Gestational diabetes</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Haemorrhage in pregnancy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Polyhydramnios</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Premature labour</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Premature rupture of membranes</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Threatened labour</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Uterine hypotonus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Umbilical cord abnormaility</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Uterine contractions during pregnancy</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Uterine contractions abnormal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Foetal hypokinesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Gestational hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Uterine irritability</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Urinary incontinence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Bladder spasm</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Ovarian cyst</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Pelvic pain</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Pruritus genital</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Uterine haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Vaginal discharge</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Vaginal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Vuvovaginal pruritus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Cervix haemorrhage uterine</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Vulvovaginal discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Genital discharge</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Vaginal erosion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Cervix oedena</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Shortened cervix</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Vulvovaginal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Bronchospasm</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis allergic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Dermatitis atopic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Dermatitis contact</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Skin striae</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Utricaria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Pruritus allergic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Director of Clinical Trials</name_or_title>
      <organization>Grünenthal GmbH</organization>
      <phone>+49 241 569 3223</phone>
      <email>clinical-trials@grunenthal.com</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/NCT02225353
org study id: EC12012/10IEI-9339
nct id: NCT02225353
lead sponsor: 
collaborator: 
has dmc: Yes
Assess the efficacy of 2 Cervical Pessaries containing 6.3 g and 7.7 g micronized
      progesterone for the prevention of preterm delivery, established through spontaneous birth
      before gestation weeks 32 (31 weeks and 6 days) and 34 (33 weeks and 6 days), when the
      pessary is inserted during weeks 16th and 24th and removed at 36 weeks and 6 days in pregnant
      women at high risk of premature birth.
Participant selection will be performed by screening the general population of pregnant women
      with single fetus monitored by the Hospital Healthcare Network, to investigate by serial
      transvaginal ultrasound performed between gestation weeks 16 (0 day to 7 days) and 24 (0 day
      to 7 days) those patients who have a cervical length between 10 mm and 25 mm, and/or women
      with a single fetus and cervical length ≥10 mm presenting one or more of the following risk
      factors:

        1. preterm birth prior to 35 (34 weeks and 6 days) weeks of gestation;

        2. premature rupture of membranes prior to 35 (34 and 6 days) weeks of gestation.

      After insertion of the pessary or beginning of the administration with vaginal progesterone
      capsules and until 28 weeks of gestation, participants in the 3 treatment groups will be
      monitored every 4 weeks at the most or more often, if the site has established so as a
      control standard. After 28 weeks, patients should be monitored every 2 weeks.

      The proportions of spontaneous preterm delivery before gestation weeks 32 and 34 will be
      compared between the control group and the 2 groups with the pessaries containing different
      doses of progesterone.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Number of Participants Not Giving Birth Before Week 32 and Week 34 of Gestation
time frame: Up to 36 weeks of gestational age
description: To assess the efficacy of Cerclage Pessaries containing 6.3 g and 7.7 g micronized progesterone for the prevention of preterm delivery, established through spontaneous parturition before gestation weeks 32 (31 weeks and 6 days) and 34 (33 weeks and 6 days), when the pessary is inserted between weeks 16 and 24 and removed at 36 weeks and 6 days in pregnant women at high risk of premature delivery.
For the purpose of this analysis, pregnancies were no longer considered as high risk for the event if delivery occurred at week 34 of gestation and beyond. Gestational age was determined by the last menstruation date and were confirmed by measurement of the craniocaudal length obtained in the first trimester ultrasound, or by measurement of the cephalic circumference in the second trimester ultrasound predominating the actual date of the last menstrual period.
The number of participants not giving birth before 32 weeks and 34 weeks are reported.
measure: Number of Participants With Premature Rupture of Membranes
time frame: Up to 36 weeks of gestational age
description: A participant with premature rupture of membrane typically recalls a sudden gush of fluid loss from the vagina, or steady loss of small amounts of fluid. Participants who reported vaginal discharge were examined by a physician.
measure: Anatomical Feature: Length of the Uterine Cervix
time frame: Up to 36 weeks of gestational age. Results are reported for all assessments from baseline through final visit, for a total of 8 visits, and for up to 36 weeks of gestational age.
description: During the pregnancy the length of the uterine cervix will be assessed. The rational is that premature birth is associated with uterine cervix shortening. The length of the cervix was determined using ultrasound examination. A positive change from baseline indicates a positive development, i.e. less likely to result in a preterm birth. The comparison between premature an normal birth initially planned by the protocol was not analyzed.
measure: Anatomical Feature: Position of the Uterine Cervix
time frame: Up to 36 weeks of gestational age. Results are reported for all assessments from baseline through final visit, for a total of 8 visits, and for up to 36 weeks of gestational age.
description: During the pregnancy the position of the uterine cervix will be assessed. The rational being that premature birth is associated with uterine cervix positioning. The position of the cervix was determined using transvaginal ultrasound examination. In the change from baseline visit a positive value change indicated that the investigator believed that the position of the cervix changed in a positive manner to facilitate a term birth. The comparison between premature an normal birth initially planned by the protocol was not analyzed. The results reported are the degrees of the cervix position relative to the longitudinal axis of the uterus.
measure: Acceptability and Tolerance of Use of the Cerclage Pessary
time frame: Up to 36 weeks of gestational age
description: A questionnaire was planned to be used to compare acceptability and tolerance in the insertion, during pregnancy and during the extraction of Cerclage Pessary.
Data from this questionnaire was not collected.
measure: Number of Adverse Events Related With the Use of Treatment
time frame: Up to 36 weeks of gestational age
description: The number of adverse events reported were analyzed as being related with the treatment as well as for unexpectedness.
arm group label: Progesterone Cervical Pessary 6.3 g
arm group type: Experimental
description: 90 pregnant women with Progesterone Cervical Pessary
arm group label: Progesterone Cervical Pessary 7.7 g
arm group type: Experimental
description: 90 pregnant women with Progesterone Cervical Pessary
arm group label: Progesterone 200 mg vaginal capsules
arm group type: Active Comparator
description: 90 pregnant women using Progesterone 200 mg vaginal capsules daily
intervention type: Drug
intervention name: Progesterone Cervical Pessary 6.3 g
description: Progesterone Cervical Pessary low dose
arm group label: Progesterone Cervical Pessary 6.3 g
intervention type: Drug
intervention name: Progesterone 200 mg vaginal capsules
description: Progesterone 200 mg vaginal capsules daily
arm group label: Progesterone 200 mg vaginal capsules
other name: Hormoral (Trade Mark) Capsules
intervention type: Drug
intervention name: Progesterone Cervical Pessary 7.7 g
description: Progesterone Cervical Pessary high dose
arm group label: Progesterone Cervical Pessary 7.7 g
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Grünenthal Study Director
role: Study Director
affiliation: Grünenthal GmbH
facility: 
facility: 
facility: 
facility: 
country: Chile
citation: Dodd JM, Crowther CA, Cincotta R, Flenady V, Robinson JS. Progesterone supplementation for preventing preterm birth: a systematic review and meta-analysis. Acta Obstet Gynecol Scand. 2005 Jun;84(6):526-33. doi: 10.1111/j.0001-6349.2005.00835.x.
PMID: 15901258
citation: Berghella V. Novel developments on cervical length screening and progesterone for preventing preterm birth. BJOG. 2009 Jan;116(2):182-7. doi: 10.1111/j.1471-0528.2008.02008.x.
PMID: 19076950
citation: Jayasooriya GS, Lamont RF. The use of progesterone and other progestational agents to prevent spontaneous preterm labour and preterm birth. Expert Opin Pharmacother. 2009 Apr;10(6):1007-16. doi: 10.1517/14656560902851403.
PMID: 19351272
citation: Newcomer J. Pessaries for the treatment of incompetent cervix and premature delivery. Obstet Gynecol Surv. 2000 Jul;55(7):443-8. doi: 10.1097/00006254-200007000-00023.
PMID: 10885649
citation: Arabin B, Halbesma JR, Vork F, Hubener M, van Eyck J. Is treatment with vaginal pessaries an option in patients with a sonographically detected short cervix? J Perinat Med. 2003;31(2):122-33. doi: 10.1515/JPM.2003.017.
PMID: 12747228
citation: Goya M, Pratcorona L, Merced C, Rodo C, Valle L, Romero A, Juan M, Rodriguez A, Munoz B, Santacruz B, Bello-Munoz JC, Llurba E, Higueras T, Cabero L, Carreras E; Pesario Cervical para Evitar Prematuridad (PECEP) Trial Group. Cervical pessary in pregnant women with a short cervix (PECEP): an open-label randomised controlled trial. Lancet. 2012 May 12;379(9828):1800-6. doi: 10.1016/S0140-6736(12)60030-0. Epub 2012 Apr 3. Erratum In: Lancet. 2012 May 12;379(9828):1790.
PMID: 22475493
responsible party type: Sponsor
mesh term: Premature Birth
mesh term: Progesterone
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 