<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/NCT03227705</url>
  </required_header>
  <id_info>
    <org_study_id>13-159</org_study_id>
    <nct_id>NCT03227705</nct_id>
  </id_info>
  <brief_title>Canadian Study on the Association of Pessary With Progesterone</brief_title>
  <acronym>CAPP</acronym>
  <official_title>Canadian Study on the Association of Pessary With Progesterone</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Université de Sherbrooke</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Centre hospitalier de l'Université de Montréal (CHUM)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>CHU de Quebec-Universite Laval</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>St. Justine's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Jewish General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Ottawa Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Queen's University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Université de Sherbrooke</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Prematurity is the leading cause of neonatal morbidity causing more than 1 million deaths&#xD;
      worldwide per year. In 2012, a randomized controlled trial (RCT) testing &quot;pessary&quot; (silicone&#xD;
      ring placed around the cervix) versus &quot;no pessary&quot; in patients with a short cervix showed a&#xD;
      4-fold reduction in the rate of spontaneous prematurity &lt;34 weeks of gestation and a&#xD;
      reduction in perinatal morbidity and mortality. This result was not found in a subsequent RCT&#xD;
      and another study on the subject had to be stopped in the face of slow recruitment.&#xD;
      Currently, the obstetric scientific community believes that other RCTs are needed before&#xD;
      using the pessary in the clinic as a therapeutic option to prevent prematurity in the&#xD;
      presence of a short cervix. However, before starting a large RCT, it is important to test the&#xD;
      feasibility of recruitment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hypothesis: A standardized recruitment process could allow the inclusion of 0.9% patient (CI&#xD;
      95%: 0,78-1.04) among women receiving a 18-23 weeks ultrasound scan.&#xD;
&#xD;
      Recruitment: Participants will be recruited, in a three-step manner, among women appointing&#xD;
      for the 18-23 weeks ultrasound scan; i) assessment of the cervical length by abdominal&#xD;
      ultrasound, ii) an endovaginal ultrasound measurement will be performed if the cervical&#xD;
      length is ≤ 30 mm, iii) enrollment and consent of the patient to the pilot study, under the&#xD;
      confirmation of the presence of a short cervix (≤ 25 mm) by the endovaginal ultrasound.&#xD;
&#xD;
      Intervention: Vaginal progesterone (200 mg/day, PROMETRIUM®, Merck Canada Inc.) until 37&#xD;
      weeks. Perforated cerclage pessaries (Dr. Arabin GmbH &amp; Co. KG) will be placed in specialized&#xD;
      clinic and will be removed at 37 weeks.&#xD;
&#xD;
      Size of the sampling and statistical analysis: This multicenter pilot study will be conducted&#xD;
      in High-Risk Pregnancies Clinics in Quebec and in Ontario.&#xD;
&#xD;
      Over the 12 months period, the investigators expect to collect data from 26 000 abdominal&#xD;
      ultrasounds. In accordance with the anticipated recruitment level of 0.9%, the investigators&#xD;
      planned on enrolling 250 women. Within those women, 125 will be assigned randomly to the&#xD;
      &quot;progesterone&quot; group and 125 to the &quot;progesterone and pessary&quot; group (1:1 ratio).&#xD;
&#xD;
      Perspective: This pilot study is designed to identify the challenges and provide strategies&#xD;
      to deal with them in a larger study. Providing its feasibility, this study will lead to a&#xD;
      definitive randomized controlled trial (including over 70 centers) to test the effectiveness&#xD;
      of pessary and progesterone in preventing preterm birth.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 4, 2018</start_date>
  <completion_date type="Actual">October 6, 2022</completion_date>
  <primary_completion_date type="Actual">October 6, 2022</primary_completion_date>
  <phase>N/A</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>
    <intervention_model_description>Randomized, controlled clinical trial.</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Recruitment feasibility</measure>
    <time_frame>Up to 24 weeks (18 to 42 weeks of gestation)</time_frame>
    <description>According to the anticipated recruitment rate, 0.9% of women having an anatomy scan could be included (95% CI, 0.78- 1.04). We will determine the % of women included in the study (until the 42 week of gestation) over women that received a anatomy scan.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Preterm delivery</measure>
    <time_frame>Before 34 weeks</time_frame>
    <description>The secondary outcome is to determine the occurrence of spontaneous preterm births before 34 weeks in the progesterone alone group &quot; without pessary harm &quot;.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">79</enrollment>
  <condition>Preterm Birth</condition>
  <condition>Short Cervix</condition>
  <arm_group>
    <arm_group_label>Intravaginal progesterone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Once the participant agrees and signs the consent form, the use of prophylactic progesterone will begin (PROMETRIUM, 200 mg in total of progesterone, 2 vaginal capsules per day at bedtime up to 36 6/7 weeks of gestation, Merck Canada Inc.)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intravaginal progesterone and pessary</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Once the participant agrees and signs the consent form, the use of prophylactic progesterone will begin (PROMETRIUM, 200 mg in total of progesterone, 2 vaginal capsules per day at bedtime, Merck Canada Inc.). Also, a perforated pessary (Dr. Arabin, cerclage pessary perforated) will be inserted. The pessary will be removed and the progesterone treatment will be stopped at 36 6/7 weeks of gestation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prometrium</intervention_name>
    <description>Intravaginal use, off label, of Prometrium</description>
    <arm_group_label>Intravaginal progesterone</arm_group_label>
    <arm_group_label>Intravaginal progesterone and pessary</arm_group_label>
    <other_name>Progesterone</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Dr. Arabin, cerclage pessary perforated</intervention_name>
    <description>A Dr. Arabin, cerclage pessary perforated will be inserted participants diagnosed with a short cervix</description>
    <arm_group_label>Intravaginal progesterone and pessary</arm_group_label>
    <other_name>Pessary</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patient with a short cervix equal to or less than 25 mm by transvaginal ultrasound&#xD;
&#xD;
          -  gestational age between 18 (0/7) and 23 (6/7) weeks of gestation according to the&#xD;
             results of the ultrasound of the first trimester, or by integrating the date of the&#xD;
             last period&#xD;
&#xD;
          -  patients who were informed of the study and agreed to sign the consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  pregnancy with a fetus with a major congenital malformation - regular and painful&#xD;
             uterine activity - history of preterm premature rupture of membranes (PPROM) - active&#xD;
             vaginal bleeding - complete and incomplete placenta previa - cerclage of the cervix in&#xD;
             place - antecedent of conisation - multiple gestation - ballooning of membranes&#xD;
             outside the cervix into the vagina - allergy/intolerance or hypersensitivity to&#xD;
             progesterone or any of its ingredients - chronic medical conditions that would&#xD;
             interfere with study participation or evaluation of treatment - vaginal administration&#xD;
             of another drug.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jean-Charles Pasquier, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Université de Sherbrooke</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Kingston General Hospital</name>
      <address>
        <city>Kingston</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ottawa Hospital</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1H 8L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre hospitalier de l'Université de Montréal</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H2X 0C1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Sainte-Justine</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H3T 1C5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CIUSSS du Centre Ouest-de-l'Île-de Montréal</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H3T 1E2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St.Mary's Hospital Center</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Québec-Université Laval</name>
      <address>
        <city>Quebec city</city>
        <state>Quebec</state>
        <zip>G1V 4G2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Université de Sherbrooke</name>
      <address>
        <city>Sherbrooke</city>
        <state>Quebec</state>
        <zip>J1H 5N4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <link>
    <url>http://capp.crc.chus.qc.ca/</url>
    <description>Clinical trial website</description>
  </link>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>July 12, 2017</study_first_submitted>
  <study_first_submitted_qc>July 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2017</study_first_posted>
  <last_update_submitted>April 5, 2023</last_update_submitted>
  <last_update_submitted_qc>April 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Université de Sherbrooke</investigator_affiliation>
    <investigator_full_name>Jean-Charles Pasquier, MD, PhD</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Preterm birth</keyword>
  <keyword>Short cervix</keyword>
  <keyword>Pessary</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>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03227705
org study id: 13-159
nct id: NCT03227705
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Prematurity is the leading cause of neonatal morbidity causing more than 1 million deaths
      worldwide per year. In 2012, a randomized controlled trial (RCT) testing "pessary" (silicone
      ring placed around the cervix) versus "no pessary" in patients with a short cervix showed a
      4-fold reduction in the rate of spontaneous prematurity <34 weeks of gestation and a
      reduction in perinatal morbidity and mortality. This result was not found in a subsequent RCT
      and another study on the subject had to be stopped in the face of slow recruitment.
      Currently, the obstetric scientific community believes that other RCTs are needed before
      using the pessary in the clinic as a therapeutic option to prevent prematurity in the
      presence of a short cervix. However, before starting a large RCT, it is important to test the
      feasibility of recruitment.
Hypothesis: A standardized recruitment process could allow the inclusion of 0.9% patient (CI
      95%: 0,78-1.04) among women receiving a 18-23 weeks ultrasound scan.

      Recruitment: Participants will be recruited, in a three-step manner, among women appointing
      for the 18-23 weeks ultrasound scan; i) assessment of the cervical length by abdominal
      ultrasound, ii) an endovaginal ultrasound measurement will be performed if the cervical
      length is ≤ 30 mm, iii) enrollment and consent of the patient to the pilot study, under the
      confirmation of the presence of a short cervix (≤ 25 mm) by the endovaginal ultrasound.

      Intervention: Vaginal progesterone (200 mg/day, PROMETRIUM®, Merck Canada Inc.) until 37
      weeks. Perforated cerclage pessaries (Dr. Arabin GmbH & Co. KG) will be placed in specialized
      clinic and will be removed at 37 weeks.

      Size of the sampling and statistical analysis: This multicenter pilot study will be conducted
      in High-Risk Pregnancies Clinics in Quebec and in Ontario.

      Over the 12 months period, the investigators expect to collect data from 26 000 abdominal
      ultrasounds. In accordance with the anticipated recruitment level of 0.9%, the investigators
      planned on enrolling 250 women. Within those women, 125 will be assigned randomly to the
      "progesterone" group and 125 to the "progesterone and pessary" group (1:1 ratio).

      Perspective: This pilot study is designed to identify the challenges and provide strategies
      to deal with them in a larger study. Providing its feasibility, this study will lead to a
      definitive randomized controlled trial (including over 70 centers) to test the effectiveness
      of pessary and progesterone in preventing preterm birth.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized, controlled clinical trial.
primary purpose: Other
masking: None (Open Label)
measure: Recruitment feasibility
time frame: Up to 24 weeks (18 to 42 weeks of gestation)
description: According to the anticipated recruitment rate, 0.9% of women having an anatomy scan could be included (95% CI, 0.78- 1.04). We will determine the % of women included in the study (until the 42 week of gestation) over women that received a anatomy scan.
measure: Preterm delivery
time frame: Before 34 weeks
description: The secondary outcome is to determine the occurrence of spontaneous preterm births before 34 weeks in the progesterone alone group " without pessary harm ".
arm group label: Intravaginal progesterone
arm group type: Active Comparator
description: Once the participant agrees and signs the consent form, the use of prophylactic progesterone will begin (PROMETRIUM, 200 mg in total of progesterone, 2 vaginal capsules per day at bedtime up to 36 6/7 weeks of gestation, Merck Canada Inc.)
arm group label: Intravaginal progesterone and pessary
arm group type: Experimental
description: Once the participant agrees and signs the consent form, the use of prophylactic progesterone will begin (PROMETRIUM, 200 mg in total of progesterone, 2 vaginal capsules per day at bedtime, Merck Canada Inc.). Also, a perforated pessary (Dr. Arabin, cerclage pessary perforated) will be inserted. The pessary will be removed and the progesterone treatment will be stopped at 36 6/7 weeks of gestation.
intervention type: Drug
intervention name: Prometrium
description: Intravaginal use, off label, of Prometrium
arm group label: Intravaginal progesterone
arm group label: Intravaginal progesterone and pessary
other name: Progesterone
intervention type: Device
intervention name: Dr. Arabin, cerclage pessary perforated
description: A Dr. Arabin, cerclage pessary perforated will be inserted participants diagnosed with a short cervix
arm group label: Intravaginal progesterone and pessary
other name: Pessary
criteria: 
gender: Female
gender based: Yes
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jean-Charles Pasquier, MD, PhD
role: Principal Investigator
affiliation: Université de Sherbrooke
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
url: http://capp.crc.chus.qc.ca/
description: Clinical trial website
responsible party type: Principal Investigator
investigator affiliation: Université de Sherbrooke
investigator full name: Jean-Charles Pasquier, MD, PhD
investigator title: MD, PhD
mesh term: Premature Birth
mesh term: Progesterone
sharing ipd: No