<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/NCT02254577</url>
  </required_header>
  <id_info>
    <org_study_id>13-0028</org_study_id>
    <secondary_id>SUSTAIN</secondary_id>
    <nct_id>NCT02254577</nct_id>
  </id_info>
  <brief_title>Vaginal Compared to Intramuscular Progesterone for Frozen Embryo Transfer</brief_title>
  <official_title>A Randomized, Three-armed, Non-Inferiority Study of Vaginal Progesterone (Endometrin®) Compared to Intramuscular Progesterone in Oil (PIO) in Infertile Subjects Undergoing Frozen Embryo Transfer (FET)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shady Grove Fertility Reproductive Science Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ferring Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Shady Grove Fertility Reproductive Science Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To determine whether the of vaginal progesterone replacement for frozen embryo transfer&#xD;
      results in equivalent live birth rates to intramuscular injection progesterone replacement.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this ongoing study is to look at whether Endometrin® (vaginal micronized&#xD;
      progesterone tablets) supplemented by intramuscular injection of progesterone in oil (PIO)&#xD;
      work as well as PIO alone for women undergoing transfer of frozen-thawed blastocyst(s).&#xD;
      Another goal of the study is to determine whether patients prefer Endometrin or PIO.&#xD;
      Endometrin® has been approved by the United States Food and Drug Administration, or FDA, &quot;to&#xD;
      support embryo implantation and early pregnancy by supplementation of corpus luteal function&#xD;
      as part of an Assisted Reproductive Technology (ART) treatment program for infertile women.&quot;&#xD;
      (FDA New Drug Approval Letter, Endometrin®, 2007). The use of Endometrin® (vaginal micronized&#xD;
      progesterone tablets) in this study is investigational. An investigational use is one that is&#xD;
      not approved by the U.S. Food and Drug Administration (FDA).&#xD;
&#xD;
      Approximately 1170 women between the ages of 18-48 who are having difficulty becoming&#xD;
      pregnant and wish to undergo frozen embryo transfer will be asked to participate. The&#xD;
      participants will be recruited from among patients of Shady Grove Fertility.&#xD;
&#xD;
      One-half of the participants who qualify and wish to take part in the ongoing study will be&#xD;
      randomized (assigned by chance, like the flip of a coin) to receive Endometrin® and an&#xD;
      intramuscular injection of PIO every third day. One-half will be randomized to receive an&#xD;
      intramuscular injection of PIO every day. This study is a type of study called an &quot;open&#xD;
      label,&quot; assessor-blind study. This means that you and your doctor will know which treatment&#xD;
      you are assigned and receive; however, the person analyzing the information obtained from the&#xD;
      study will not know which patients received which study treatments.&#xD;
&#xD;
      Patients enrolling in the study will receive the medications for their frozen embryo transfer&#xD;
      cycle free of charge.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">April 27, 2018</completion_date>
  <primary_completion_date type="Actual">April 27, 2018</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Live Birth</measure>
    <time_frame>~40 weeks post Frozen Embryo Transfer</time_frame>
    <description>Live born infant at 23 weeks' estimated gestational age or greater.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Ongoing Implantation Rate</measure>
    <time_frame>7-8 weeks after embryo transfer</time_frame>
    <description>maximum # fetal heartbeats divided by total number of embryos transferred</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Implantation rate</measure>
    <time_frame>5-6 weeks post embryo transfer</time_frame>
    <description>Maximum number of gestational sacs, divided by total number of embryos transferred</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biochemical pregnancy</measure>
    <time_frame>~10 days following embryo transfer</time_frame>
    <description>detection of beta hCG (pregnancy hormone) above 5 IU/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical pregnancy</measure>
    <time_frame>5-6 weeks following embryo transfer</time_frame>
    <description>Presence of gestational sac(s) at 5-6 weeks post ET</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum progesterone level</measure>
    <time_frame>~10 days following embryo transfer</time_frame>
    <description>blood draw</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient satisfaction with Endometrin® vs. intramuscular progesterone in oil</measure>
    <time_frame>between 0 and 10 days following embryo transfer</time_frame>
    <description>As assessed by brief, optional online survey</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1139</enrollment>
  <condition>Infertility</condition>
  <arm_group>
    <arm_group_label>Endometrin® plus Progesterone in Oil (PIO)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects in all arms will undergo the standard monitoring appointments and therapies involved in a frozen embryo transfer cycle. Patients randomized to the Endometrin® plus PIO arm will take progesterone as 2 100mg tablets of Endometrin® inserted vaginally twice daily. In addition, on the first day of Endometrin® therapy, patients randomized to this arm will take a 50mg intramuscular injection (1mL) of PIO and will repeat this injection every third day. Patients in this arm will undergo Frozen Embryo Transfer on the fifth day of Endometrin® therapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Progesterone in Oil (PIO) Alone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects in all arms will undergo the standard monitoring appointments and therapies involved in a frozen embryo transfer cycle. Patients randomized to the PIO Only arm will take progesterone as a daily 50mg intramuscular injection (1mL) of PIO and will undergo Frozen Embryo Transfer on the sixth day of taking this medication.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Endometrin® plus Progesterone in Oil (PIO)</intervention_name>
    <arm_group_label>Endometrin® plus Progesterone in Oil (PIO)</arm_group_label>
    <other_name>Vaginal Micronized Progesterone Tablet</other_name>
    <other_name>Progesterone in Sesame Oil Injection</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Progesterone in Oil (PIO) Only</intervention_name>
    <arm_group_label>Progesterone in Oil (PIO) Alone</arm_group_label>
    <other_name>Progesterone in Sesame Oil Injection</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed informed consent&#xD;
&#xD;
          2. Female age between 18 and 48 years&#xD;
&#xD;
          3. Having available blastocyst(s) frozen by vitrification method at our center (Shady&#xD;
             Grove Fertility).&#xD;
&#xD;
          4. Standard eligibility criteria to undergo frozen blastocyst transfer at Shady Grove&#xD;
             Fertility.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Requires fresh embryos or surrogate carrier&#xD;
&#xD;
          2. Embryos from frozen oocytes and embryos frozen more than once&#xD;
&#xD;
          3. Any embryo cryopreserved by slow freeze method and/or prior to blastocyst stage&#xD;
&#xD;
          4. Presence of any clinically relevant systemic disease contraindicated for ART&#xD;
&#xD;
          5. History of more than 3 failed cycles in previous ART attempts and/or more than 3&#xD;
             recurrent pregnancy losses after ET&#xD;
&#xD;
          6. Surgical or medical condition or requirement for medication, which may interfere with&#xD;
             absorption, distribution, metabolism, or excretion of the drugs to be used&#xD;
&#xD;
          7. Subjects with a body mass index (BMI) of &lt;18 or &gt;38 kg/m2 at screening&#xD;
&#xD;
          8. Current or recent substance abuse, including alcohol and tobacco. (Note: Subjects who&#xD;
             stopped tobacco usage at least 3 months prior to screening visit will be allowed)&#xD;
&#xD;
          9. Currently breast feeding, pregnant, or having (a) contraindication(s) to pregnancy&#xD;
&#xD;
         10. Refusal or inability to comply with the requirements of the protocol for any reason,&#xD;
             including scheduled clinic visits and laboratory tests&#xD;
&#xD;
         11. Trophectoderm or blastomere biopsy of the blastocyst(s) to be transferred.&#xD;
&#xD;
         12. Documented intolerance or allergy to any of the medications used, including the study&#xD;
             medication&#xD;
&#xD;
         13. Participation in any experimental drug study within 60 days prior to screening&#xD;
&#xD;
         14. If a subject undergoes more than two frozen blastocyst transfers meeting study&#xD;
             criteria, she will only be eligible to enroll in the study for two of these.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>48 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Shady Grove Fertility Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20006</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shady Grove Fertility Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shady Grove Fertility Center</name>
      <address>
        <city>Annapolis</city>
        <state>Maryland</state>
        <zip>21401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shady Grove Fertility Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shady Grove Fertility Center</name>
      <address>
        <city>Bel Air</city>
        <state>Maryland</state>
        <zip>21015</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shady Grove Fertility Center</name>
      <address>
        <city>Columbia</city>
        <state>Maryland</state>
        <zip>21044</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shady Grove Fertility Center</name>
      <address>
        <city>Frederick</city>
        <state>Maryland</state>
        <zip>21702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shady Grove Fertility Center</name>
      <address>
        <city>Rockville</city>
        <state>Maryland</state>
        <zip>20850</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shady Grove Fertility Center</name>
      <address>
        <city>Towson</city>
        <state>Maryland</state>
        <zip>21204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shady Grove Fertility</name>
      <address>
        <city>Camp Hill</city>
        <state>Pennsylvania</state>
        <zip>17011</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shady Grove Fertility Center</name>
      <address>
        <city>Chesterbrook</city>
        <state>Pennsylvania</state>
        <zip>19087</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shady Grove Fertility Center</name>
      <address>
        <city>Annandale</city>
        <state>Virginia</state>
        <zip>22003</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shady Grove Fertility Center</name>
      <address>
        <city>Leesburg</city>
        <state>Virginia</state>
        <zip>20176</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shady Grove Fertility Center</name>
      <address>
        <city>Woodbridge</city>
        <state>Virginia</state>
        <zip>22192</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Shapiro DB, Pappadakis JA, Ellsworth NM, Hait HI, Nagy ZP. Progesterone replacement with vaginal gel versus i.m. injection: cycle and pregnancy outcomes in IVF patients receiving vitrified blastocysts. Hum Reprod. 2014 Aug;29(8):1706-11. doi: 10.1093/humrep/deu121. Epub 2014 May 20.</citation>
    <PMID>24847018</PMID>
  </reference>
  <reference>
    <citation>Feinberg EC, Beltsos AN, Nicolaou E, Marut EL, Uhler ML. Endometrin as luteal phase support in assisted reproduction. Fertil Steril. 2013 Jan;99(1):174-178.e1. doi: 10.1016/j.fertnstert.2012.09.019. Epub 2012 Nov 6.</citation>
    <PMID>23137759</PMID>
  </reference>
  <reference>
    <citation>Paulson RJ, Collins MG, Yankov VI. Progesterone pharmacokinetics and pharmacodynamics with 3 dosages and 2 regimens of an effervescent micronized progesterone vaginal insert. J Clin Endocrinol Metab. 2014 Nov;99(11):4241-9. doi: 10.1210/jc.2013-3937. Epub 2014 Feb 25.</citation>
    <PMID>24606090</PMID>
  </reference>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>September 29, 2014</study_first_submitted>
  <study_first_submitted_qc>October 1, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 2, 2014</study_first_posted>
  <last_update_submitted>July 31, 2018</last_update_submitted>
  <last_update_submitted_qc>July 31, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 2, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Infertility</keyword>
  <keyword>Progesterone</keyword>
  <keyword>ART</keyword>
  <keyword>IVF</keyword>
  <keyword>FET</keyword>
  <keyword>FBT</keyword>
  <keyword>Frozen Embryo Transfer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infertility</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Progesterone</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02254577
org study id: 13-0028
secondary id: SUSTAIN
nct id: NCT02254577
lead sponsor: 
collaborator: 
has dmc: Yes
To determine whether the of vaginal progesterone replacement for frozen embryo transfer
      results in equivalent live birth rates to intramuscular injection progesterone replacement.
The purpose of this ongoing study is to look at whether Endometrin® (vaginal micronized
      progesterone tablets) supplemented by intramuscular injection of progesterone in oil (PIO)
      work as well as PIO alone for women undergoing transfer of frozen-thawed blastocyst(s).
      Another goal of the study is to determine whether patients prefer Endometrin or PIO.
      Endometrin® has been approved by the United States Food and Drug Administration, or FDA, "to
      support embryo implantation and early pregnancy by supplementation of corpus luteal function
      as part of an Assisted Reproductive Technology (ART) treatment program for infertile women."
      (FDA New Drug Approval Letter, Endometrin®, 2007). The use of Endometrin® (vaginal micronized
      progesterone tablets) in this study is investigational. An investigational use is one that is
      not approved by the U.S. Food and Drug Administration (FDA).

      Approximately 1170 women between the ages of 18-48 who are having difficulty becoming
      pregnant and wish to undergo frozen embryo transfer will be asked to participate. The
      participants will be recruited from among patients of Shady Grove Fertility.

      One-half of the participants who qualify and wish to take part in the ongoing study will be
      randomized (assigned by chance, like the flip of a coin) to receive Endometrin® and an
      intramuscular injection of PIO every third day. One-half will be randomized to receive an
      intramuscular injection of PIO every day. This study is a type of study called an "open
      label," assessor-blind study. This means that you and your doctor will know which treatment
      you are assigned and receive; however, the person analyzing the information obtained from the
      study will not know which patients received which study treatments.

      Patients enrolling in the study will receive the medications for their frozen embryo transfer
      cycle free of charge.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Live Birth
time frame: ~40 weeks post Frozen Embryo Transfer
description: Live born infant at 23 weeks' estimated gestational age or greater.
measure: Ongoing Implantation Rate
time frame: 7-8 weeks after embryo transfer
description: maximum # fetal heartbeats divided by total number of embryos transferred
measure: Implantation rate
time frame: 5-6 weeks post embryo transfer
description: Maximum number of gestational sacs, divided by total number of embryos transferred
measure: Biochemical pregnancy
time frame: ~10 days following embryo transfer
description: detection of beta hCG (pregnancy hormone) above 5 IU/L
measure: Clinical pregnancy
time frame: 5-6 weeks following embryo transfer
description: Presence of gestational sac(s) at 5-6 weeks post ET
measure: Serum progesterone level
time frame: ~10 days following embryo transfer
description: blood draw
measure: Patient satisfaction with Endometrin® vs. intramuscular progesterone in oil
time frame: between 0 and 10 days following embryo transfer
description: As assessed by brief, optional online survey
arm group label: Endometrin® plus Progesterone in Oil (PIO)
arm group type: Experimental
description: Subjects in all arms will undergo the standard monitoring appointments and therapies involved in a frozen embryo transfer cycle. Patients randomized to the Endometrin® plus PIO arm will take progesterone as 2 100mg tablets of Endometrin® inserted vaginally twice daily. In addition, on the first day of Endometrin® therapy, patients randomized to this arm will take a 50mg intramuscular injection (1mL) of PIO and will repeat this injection every third day. Patients in this arm will undergo Frozen Embryo Transfer on the fifth day of Endometrin® therapy.
arm group label: Progesterone in Oil (PIO) Alone
arm group type: Active Comparator
description: Subjects in all arms will undergo the standard monitoring appointments and therapies involved in a frozen embryo transfer cycle. Patients randomized to the PIO Only arm will take progesterone as a daily 50mg intramuscular injection (1mL) of PIO and will undergo Frozen Embryo Transfer on the sixth day of taking this medication.
intervention type: Drug
intervention name: Endometrin® plus Progesterone in Oil (PIO)
arm group label: Endometrin® plus Progesterone in Oil (PIO)
other name: Vaginal Micronized Progesterone Tablet
other name: Progesterone in Sesame Oil Injection
intervention type: Drug
intervention name: Progesterone in Oil (PIO) Only
arm group label: Progesterone in Oil (PIO) Alone
other name: Progesterone in Sesame Oil Injection
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 48 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
citation: Shapiro DB, Pappadakis JA, Ellsworth NM, Hait HI, Nagy ZP. Progesterone replacement with vaginal gel versus i.m. injection: cycle and pregnancy outcomes in IVF patients receiving vitrified blastocysts. Hum Reprod. 2014 Aug;29(8):1706-11. doi: 10.1093/humrep/deu121. Epub 2014 May 20.
PMID: 24847018
citation: Feinberg EC, Beltsos AN, Nicolaou E, Marut EL, Uhler ML. Endometrin as luteal phase support in assisted reproduction. Fertil Steril. 2013 Jan;99(1):174-178.e1. doi: 10.1016/j.fertnstert.2012.09.019. Epub 2012 Nov 6.
PMID: 23137759
citation: Paulson RJ, Collins MG, Yankov VI. Progesterone pharmacokinetics and pharmacodynamics with 3 dosages and 2 regimens of an effervescent micronized progesterone vaginal insert. J Clin Endocrinol Metab. 2014 Nov;99(11):4241-9. doi: 10.1210/jc.2013-3937. Epub 2014 Feb 25.
PMID: 24606090
responsible party type: Sponsor
mesh term: Infertility
mesh term: Progesterone