<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/NCT03292731</url>
  </required_header>
  <id_info>
    <org_study_id>PRO16110007</org_study_id>
    <secondary_id>U54HD047905-11</secondary_id>
    <secondary_id>STUDY19020368</secondary_id>
    <nct_id>NCT03292731</nct_id>
  </id_info>
  <brief_title>Relationship Between Plasma Concentration of Hydroxyprogesterone Caproate (17-OHPC) and Preterm Birth</brief_title>
  <acronym>PRO</acronym>
  <official_title>Relationship Between Plasma Concentration of (Hydroxyprogesterone Caproate) 17-OHPC and Preterm Birth</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Steve N. Caritis, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study plans to determine the relationship between plasma concentrations of 17-OHPC&#xD;
      (hydroxyprogesterone caproate) and the rate of preterm birth. The study is a randomized, open&#xD;
      label study of pregnant women with one or more prior spontaneous preterm births. Subjects are&#xD;
      randomized to a weekly single injection of either 250 or 500mg 17-OHPC (hydroxyprogesterone&#xD;
      caproate).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will determine the association between plasma concentrations of 17-OHPC&#xD;
      (hydroxyprogesterone caproate) and the rate of preterm birth and will evaluate the impact of&#xD;
      several potential covariates on plasma concentrations of 17-OHPC and its efficacy. 17-OHPC&#xD;
      (hydroxyprogesterone caproate) administration has proven effective in reducing preterm births&#xD;
      in high risk groups but the current dose of 250mg administered IM is thought to be an&#xD;
      inadequate for a substantial portion of women receiving the therapy. The potential benefit of&#xD;
      identifying a therapeutic concentration range and of optimizing the dosage of 17-OHPC are&#xD;
      substantial.&#xD;
&#xD;
      Pregnant subjects with a history of a prior spontaneous preterm birth with be randomized to&#xD;
      either the 250mg or 500mg weekly intramuscular injections. All subjects will have trough&#xD;
      blood samples collected immediately prior to their second injection of the 17-OHPC, at 26-30&#xD;
      weeks (but only after a minimum of 7 injections have been administered) , 6-9 weeks later and&#xD;
      at the time of delivery. Another tube of maternal blood will be collected during one of the&#xD;
      scheduled blood samples for genotyping. A cord blood specimen will also be collected and with&#xD;
      consent, a cord blood specimen will be collected for genetic studies of the infant.&#xD;
      Investigators will also collect a small sample of the placenta after delivery.&#xD;
&#xD;
      In order to enhance sample size for this trial, investigators will also enroll a separate&#xD;
      group of subjects (ancillary cohort) who are not in the randomized clinical trial (RCT)&#xD;
      described above. Women already receiving 250 mg 17-OHPC weekly from their healthcare provider&#xD;
      as part of their standard of care will be approached prior to 26 weeks gestation. This will&#xD;
      be an observational cohort and subjects enrolled in the ancillary cohort will not be&#xD;
      randomized, as they are already receiving the 250 mg dose. Research staff will not administer&#xD;
      the study drug to subjects enrolled in the ancillary cohort. These subjects will be asked to&#xD;
      provide two blood samples: one at 26-30 weeks and one 6-9 weeks later, which will be utilized&#xD;
      to address the primary objective of the study.&#xD;
&#xD;
      In response to the addition of the ancillary cohort, randomization for subjects in the RCT&#xD;
      will be 2:1 for the 500 mg vs the 250 mg dose. The ancillary study will be implemented&#xD;
      initially at the UPITT site only but may be expanded to other sites, as required.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 12, 2018</start_date>
  <completion_date type="Actual">September 2, 2021</completion_date>
  <primary_completion_date type="Actual">September 2, 2021</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>open labelled rct</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>relation of preterm birth to the plasma concentration of 17-OHPC (hydroxyprogesterone caproate)</measure>
    <time_frame>Plasma 17-OHPC concentration at 26-30 weeks</time_frame>
    <description>Determine the plasma concentration of 17-OHPC at 26-30 weeks gestation and relate the concentrations of 17-OHPC to the incidence of preterm birth.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">160</enrollment>
  <condition>Preterm Birth</condition>
  <arm_group>
    <arm_group_label>hydroxyprogesterone caproate 250 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Pregnant subject will receive 250mg of hydroxyprogesterone caproate Intramuscular injection weekly from 16 0/7-36 6/7 weeks or delivery which ever occurs first.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>hydroxyprogesterone caproate 500 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pregnant subject will receive 500mg of hydroxyprogesterone caproate Intramuscular injection weekly from 16 0/7-36 6/7 weeks or delivery which ever occurs first.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydroxyprogesterone 250 Mg</intervention_name>
    <description>Pregnant subjects randomized to this study arm will receive a weekly Intramuscular injection of 250mg hydroxyprogesterone caproate injection weekly from 16 0/7 to 36 6/7 weeks or delivery which ever is first.</description>
    <arm_group_label>hydroxyprogesterone caproate 250 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>hydroxyprogesterone 500mg</intervention_name>
    <description>Pregnant subjects randomized to this study arm will receive a weekly Intramuscular injection of 500mg hydroxyprogesterone caproate injection weekly from 16 0/7 to 36 6/7 weeks or delivery which ever is first.</description>
    <arm_group_label>hydroxyprogesterone caproate 500 mg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        1. Randomized Clinical Trial Eligibility Criteria:&#xD;
&#xD;
             Inclusion Criteria:&#xD;
&#xD;
               -  pregnant with a prior preterm birth 16 0/7-35 6/7 weeks from spontaneous labor or&#xD;
                  PPROM,&#xD;
&#xD;
               -  current gestational age &lt;22 weeks,&#xD;
&#xD;
               -  pregnant with one baby&#xD;
&#xD;
               -  age between 18-45 years&#xD;
&#xD;
               -  able to give consent and undergo study procedures&#xD;
&#xD;
             Exclusion Criteria:&#xD;
&#xD;
               -  plans for cerclage at enrollment, plan for progesterone treatment other than&#xD;
                  study medications at enrollment&#xD;
&#xD;
               -  known fetal anomaly or chromosomal anomaly that could affect gestational age at&#xD;
                  delivery&#xD;
&#xD;
               -  malformation of the uterus or known cervical length &lt;2.5cm&#xD;
&#xD;
               -  participation in another trial that may affect gestational age at delivery&#xD;
&#xD;
               -  planned delivery where outcome data cannot be collected&#xD;
&#xD;
               -  medical or obstetrical complication that may affect gestational age at delivery,&#xD;
                  such as active ulcerative colitis, liver tumors, liver disease/failure, renal&#xD;
                  disease/failure, undiagnosed vaginal bleeding unrelated to pregnancy, or&#xD;
                  hypertension requiring 2 or more agents&#xD;
&#xD;
               -  Current or history of thrombosis or thromboembolic disorders&#xD;
&#xD;
               -  known or suspected breast cancer, other hormone-sensitive cancer, or a history of&#xD;
                  these conditions&#xD;
&#xD;
               -  moderately severe depression (PHQ-9 score ≥ 15, EPDS score of &gt;13, or suicidal&#xD;
                  ideation)&#xD;
&#xD;
          2. Ancillary Cohort Eligibility Criteria:&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Pregnant female with documented prior birth between 16 0/7- 35 6/7 week gestation from&#xD;
             spontaneous preterm labor or preterm premature rupture of membranes&#xD;
&#xD;
          -  Receiving 250 mg 17-OHPC weekly- must be compliant with that treatment based on&#xD;
             interview and reviewing the medical record&#xD;
&#xD;
          -  Gestational age (GA) &lt;26 weeks, based on study determined GA&#xD;
&#xD;
          -  Singleton gestation&#xD;
&#xD;
          -  Age between 18 - 45 years&#xD;
&#xD;
          -  Able to give informed consent and undergo study procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inclusion in the RCT of 250 vs 500 mg OPRC study&#xD;
&#xD;
          -  Cerclage in place&#xD;
&#xD;
          -  Plan for progesterone treatment other than study medication&#xD;
&#xD;
          -  Known major fetal anomaly or chromosomal anomalies that might affect gestational age&#xD;
             at delivery&#xD;
&#xD;
          -  Malformation of uterus (uterine didelphus, septate uterus or bicornuate uterus) or&#xD;
             known cervical length &lt;2.5 cm&#xD;
&#xD;
          -  Participation in another trial that may affect gestational age at delivery&#xD;
&#xD;
          -  Planned delivery at other institution where pregnancy outcome data cannot be obtained&#xD;
&#xD;
          -  Medical or obstetrical complication that might affect gestational age at delivery,&#xD;
             such as active ulcerative colitis, liver tumors, liver disease/failure, renal&#xD;
             disease/failure, undiagnosed vaginal bleeding unrelated to pregnancy, or hypertension&#xD;
             requiring 2 or more agents&#xD;
&#xD;
          -  Current or history of thrombosis or thromboembolic disorder.&#xD;
&#xD;
          -  Known or suspected breast cancer, other hormone-sensitive cancer, or a history of&#xD;
             these conditions.&#xD;
&#xD;
          -  Moderately severe depression (PHQ-9 score ≥15, EPDS score of &gt;13, or suicidal&#xD;
             ideation)- based on criteria in the RCT&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Study of pregnant participants</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Steve N Caritis, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh-Magee Womens Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Medical Branch</name>
      <address>
        <city>Galveston</city>
        <state>Texas</state>
        <zip>77555</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>September 20, 2017</study_first_submitted>
  <study_first_submitted_qc>September 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 26, 2017</study_first_posted>
  <last_update_submitted>September 9, 2021</last_update_submitted>
  <last_update_submitted_qc>September 9, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 10, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Steve N. Caritis, MD</investigator_full_name>
    <investigator_title>Professor, Department of OB/Gyn/RS</investigator_title>
  </responsible_party>
  <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>17 alpha-Hydroxyprogesterone Caproate</mesh_term>
    <mesh_term>11-hydroxyprogesterone</mesh_term>
  </intervention_browse>
  <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>July 15, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/31/NCT03292731/Prot_017.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 16, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/31/NCT03292731/ICF_018.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <pending_results>
    <submitted>August 26, 2022</submitted>
    <submission_canceled>September 13, 2022</submission_canceled>
    <submitted>April 28, 2023</submitted>
    <returned>May 26, 2023</returned>
    <submitted>August 10, 2023</submitted>
    <returned>August 30, 2023</returned>
  </pending_results>
  <!-- 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/NCT03292731
org study id: PRO16110007
secondary id: U54HD047905-11
secondary id: STUDY19020368
nct id: NCT03292731
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The study plans to determine the relationship between plasma concentrations of 17-OHPC
      (hydroxyprogesterone caproate) and the rate of preterm birth. The study is a randomized, open
      label study of pregnant women with one or more prior spontaneous preterm births. Subjects are
      randomized to a weekly single injection of either 250 or 500mg 17-OHPC (hydroxyprogesterone
      caproate).
The study will determine the association between plasma concentrations of 17-OHPC
      (hydroxyprogesterone caproate) and the rate of preterm birth and will evaluate the impact of
      several potential covariates on plasma concentrations of 17-OHPC and its efficacy. 17-OHPC
      (hydroxyprogesterone caproate) administration has proven effective in reducing preterm births
      in high risk groups but the current dose of 250mg administered IM is thought to be an
      inadequate for a substantial portion of women receiving the therapy. The potential benefit of
      identifying a therapeutic concentration range and of optimizing the dosage of 17-OHPC are
      substantial.

      Pregnant subjects with a history of a prior spontaneous preterm birth with be randomized to
      either the 250mg or 500mg weekly intramuscular injections. All subjects will have trough
      blood samples collected immediately prior to their second injection of the 17-OHPC, at 26-30
      weeks (but only after a minimum of 7 injections have been administered) , 6-9 weeks later and
      at the time of delivery. Another tube of maternal blood will be collected during one of the
      scheduled blood samples for genotyping. A cord blood specimen will also be collected and with
      consent, a cord blood specimen will be collected for genetic studies of the infant.
      Investigators will also collect a small sample of the placenta after delivery.

      In order to enhance sample size for this trial, investigators will also enroll a separate
      group of subjects (ancillary cohort) who are not in the randomized clinical trial (RCT)
      described above. Women already receiving 250 mg 17-OHPC weekly from their healthcare provider
      as part of their standard of care will be approached prior to 26 weeks gestation. This will
      be an observational cohort and subjects enrolled in the ancillary cohort will not be
      randomized, as they are already receiving the 250 mg dose. Research staff will not administer
      the study drug to subjects enrolled in the ancillary cohort. These subjects will be asked to
      provide two blood samples: one at 26-30 weeks and one 6-9 weeks later, which will be utilized
      to address the primary objective of the study.

      In response to the addition of the ancillary cohort, randomization for subjects in the RCT
      will be 2:1 for the 500 mg vs the 250 mg dose. The ancillary study will be implemented
      initially at the UPITT site only but may be expanded to other sites, as required.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: open labelled rct
primary purpose: Treatment
masking: None (Open Label)
measure: relation of preterm birth to the plasma concentration of 17-OHPC (hydroxyprogesterone caproate)
time frame: Plasma 17-OHPC concentration at 26-30 weeks
description: Determine the plasma concentration of 17-OHPC at 26-30 weeks gestation and relate the concentrations of 17-OHPC to the incidence of preterm birth.
arm group label: hydroxyprogesterone caproate 250 mg
arm group type: Active Comparator
description: Pregnant subject will receive 250mg of hydroxyprogesterone caproate Intramuscular injection weekly from 16 0/7-36 6/7 weeks or delivery which ever occurs first.
arm group label: hydroxyprogesterone caproate 500 mg
arm group type: Experimental
description: Pregnant subject will receive 500mg of hydroxyprogesterone caproate Intramuscular injection weekly from 16 0/7-36 6/7 weeks or delivery which ever occurs first.
intervention type: Drug
intervention name: Hydroxyprogesterone 250 Mg
description: Pregnant subjects randomized to this study arm will receive a weekly Intramuscular injection of 250mg hydroxyprogesterone caproate injection weekly from 16 0/7 to 36 6/7 weeks or delivery which ever is first.
arm group label: hydroxyprogesterone caproate 250 mg
intervention type: Drug
intervention name: hydroxyprogesterone 500mg
description: Pregnant subjects randomized to this study arm will receive a weekly Intramuscular injection of 500mg hydroxyprogesterone caproate injection weekly from 16 0/7 to 36 6/7 weeks or delivery which ever is first.
arm group label: hydroxyprogesterone caproate 500 mg
criteria: 
gender: Female
gender based: Yes
gender description: Study of pregnant participants
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Steve N Caritis, MD
role: Principal Investigator
affiliation: University of Pittsburgh
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Steve N. Caritis, MD
investigator title: Professor, Department of OB/Gyn/RS
mesh term: Premature Birth
mesh term: 17 alpha-Hydroxyprogesterone Caproate
mesh term: 11-hydroxyprogesterone
provided document: 
provided document: 
submitted: August 26, 2022
submission canceled: September 13, 2022
submitted: April 28, 2023
returned: May 26, 2023
submitted: August 10, 2023
returned: August 30, 2023