<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/NCT03230825</url>
  </required_header>
  <id_info>
    <org_study_id>0263-16</org_study_id>
    <nct_id>NCT03230825</nct_id>
  </id_info>
  <brief_title>Oral Contraceptive Pills Versus Expectant Management for Retained Pregnancy Products</brief_title>
  <official_title>Oral Contraceptive Pills Versus Expectant Management for Retained Pregnancy Products After a First Trimester Miscarriage: a Randomized Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Meir Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Meir Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      We speculate that the use of combined oral contraceptives may be a possible solution to&#xD;
      promote the management of retained pregnancy products versus expectant management. By&#xD;
      withdrawing the pill, the endometrium is expected to shed in a synchronized fashion (estrogen&#xD;
      and progestin withdrawal bleeding and may also shed the retained products of conception and&#xD;
      avoid a surgical procedure with its related potential complications.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Miscarriage is a common event in general gynaecological practice, and is an age-dependent&#xD;
      outcome. It is estimated -that approximately 20 percent of clinically recognized pregnancies&#xD;
      will result in a miscarriage, and the prevalence is much higher if preclinical pregnancies&#xD;
      are included as well .Failure to pass the contents of the pregnancy is reported in 15% of&#xD;
      patients going through a spontaneous 1st trimester miscarriage and a similar rate in patients&#xD;
      going through an induced medical abortion after a spontaneous pregnancy loss (miscarriage)&#xD;
      and planned pregnancy termination using PGE1 (MisWe speculate that the use of combined oral&#xD;
      contraceptives may be a possible solution to promote the management of retained pregnancy&#xD;
      products versus expectant management. The exposure to combined oral contraceptives is known&#xD;
      to induce secretory and decidual changes in the endometrium .By withdrawing the pill, the&#xD;
      endometrium is expected to shed in a synchronized fashion (estrogen and progestin withdrawal&#xD;
      bleeding). We hypothesize that such withdrawal bleeding may also shed the retained products&#xD;
      of conception and avoid a surgical procedure with its related potential complications.&#xD;
      oprostol).&#xD;
&#xD;
      All patients diagnosed with RPOC according to the inclusion and exclusion criteria , will be&#xD;
      asked to give their informed consent to take part in the study.&#xD;
&#xD;
      Once informed consent forms are signed, the patient will be randomized (using a randomization&#xD;
      table handled by a 3rd party) into one of 2 groups:&#xD;
&#xD;
        1. Expectant management of 3 weeks and a follow up visit a week after.&#xD;
&#xD;
        2. Oral contraceptive agent, given for free, for 3 weeks and a follow up visit a week after&#xD;
           treatment withdrawal.&#xD;
&#xD;
      We wish to emphasize that the current management in our ward is expectant management in the&#xD;
      population eligible for this study.&#xD;
&#xD;
      All US scans will be performed by 2 qualified sonographers using a 7.5 MHz transvaginal&#xD;
      transducer. 2D images in both sagittal and axial planes will be obtained. Sonographic&#xD;
      features to be evaluated are: endometrial maximal thickness measured in the sagittal plan,&#xD;
      presence or absence and size of an endometrial mass (3 dimensions) and grading of endometrial&#xD;
      vascularity. Vascularity will be graded as type 0, 1, 2 or 3 defining no detectable, minimal&#xD;
      (less then myometrium), moderate (nearly equal to myometrium) or marked vascularity&#xD;
      respectively (4).&#xD;
&#xD;
      At enrollment the patient will be monitored and interviewed for the following variables :&#xD;
&#xD;
      Age, BMI, OB - GYN history, smoking status, Blood pressure, pulse rate,Temperature, blood&#xD;
      count, HCG levels.&#xD;
&#xD;
      All patients will be invited to a follow up visit 3 weeks after randomization. The follow up&#xD;
      visit will include again an ultrasound scan as described above.&#xD;
&#xD;
      In any case the patient is reporting a menstrual bleeding/ abdominal pain/ fever she will&#xD;
      contact the 24hr available ER of the ward and will be evaluated for complications. After&#xD;
      evaluation is completed the principal investigator will be contacted and the case will be&#xD;
      discussed as for the need for additional measures and documented in the research file.&#xD;
&#xD;
      In the planned 4 week post randomization visit the following parameters will be monitored:&#xD;
&#xD;
      Blood pressure, pulse rate, Temperature, blood count, HCG levels as well as a review of any&#xD;
      symptoms.&#xD;
&#xD;
      Following the interview a trans-vaginal scan will be performed in order to evaluate the&#xD;
      cavity and any retained products existence and any presence of blood flow in case of a&#xD;
      positive diagnosis.&#xD;
&#xD;
      In any case of retained products detected by ultrasound we will recommend a surgical&#xD;
      hysteroscopy.&#xD;
&#xD;
      The oral contraceptives will be donated by DEXCEL LTD, ISRAEL to the hospital pharmacy, where&#xD;
      it will be stored.&#xD;
&#xD;
      Brand name :FLAME containing 0.02 mg Ethinylestradiol and 0.075 mg Gestodene. Israeli&#xD;
      authorities demand that a drug which is tested in a research will be provided to the&#xD;
      participant without charging.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">September 2017</start_date>
  <completion_date type="Anticipated">December 2018</completion_date>
  <primary_completion_date type="Anticipated">September 2018</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>Once informed consent forms are signed, the patient will be randomized (using a randomization table handled by a 3rd party) into one of 2 groups:&#xD;
Expectant management of 3 weeks and a follow up visit a week after.&#xD;
Oral contraceptive agent, given for free, for 3 weeks and a follow up visit a week after treatment withdrawal.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>Data analysis will be performed according to group code .</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>persistent retained pregnancy products rate</measure>
    <time_frame>4 weeks</time_frame>
    <description>rate</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Retained Products of Conception Post Abortion</condition>
  <arm_group>
    <arm_group_label>Oral contraceptives</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral contraceptive agent, given for free, for 3 weeks and a follow up visit a week after treatment withdrawal.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Expectant management</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Expectant management for 3 weeks and a follow up visit a week later.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oral contraceptive</intervention_name>
    <description>Daily oral contraceptive agent for 3 weeks (FLAME, containing 0.02 mg Ethinylestradiol and 0.075 mg Gestodene)</description>
    <arm_group_label>Oral contraceptives</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Expectant management</intervention_name>
    <description>No intervention and a follow up visit a wewk later</description>
    <arm_group_label>Expectant management</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients going through a Misoprostol or Misoprostol/Mifepristone induced procedure&#xD;
             after a spontaneous 1st trimester pregnancy loss or as a 1st trimester planned&#xD;
             pregnancy termination and present retained pregnancy products by a trans-vaginal&#xD;
             ultrasound scan.&#xD;
&#xD;
          2. Patients after a surgical evacuation of pregnancy products (dilatation and curettage -&#xD;
             D&amp;C) of a 1st trimester miscarriage and present retained pregnancy products by a&#xD;
             trans-vaginal ultrasound scan.&#xD;
&#xD;
          3. All retained products included are of a previously confirmed intra-uterine&#xD;
             pregnancies.&#xD;
&#xD;
          4. Asymptomatic patients or mild symptoms of bleeding (spotting).&#xD;
&#xD;
          5. Presence of a measurable hyperechoic material by 2 dimensional TVUS&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Retained products with any of the following clinical presentations : more than a mild&#xD;
             vaginal bleeding, hemodynamic instability, signs of infection and/or abdominal pain.&#xD;
&#xD;
          2. Any suspicion of a molar pregnancy.&#xD;
&#xD;
          3. A known contra-indication for the use of oral contraceptives&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Retaiend pregnancy products</gender_description>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>54 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anat Hershko Klement, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Meir Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Anat Hershko Klement, MD</last_name>
    <phone>+972549170084</phone>
    <email>anat.klement@gmail.com</email>
  </overall_contact>
  <reference>
    <citation>Chen BA, Creinin MD. Medical management of early pregnancy failure: efficacy. Semin Reprod Med. 2008 Sep;26(5):411-22. doi: 10.1055/s-0028-1087107. Epub 2008 Sep 29.</citation>
    <PMID>18825609</PMID>
  </reference>
  <reference>
    <citation>Griebel CP, Halvorsen J, Golemon TB, Day AA. Management of spontaneous abortion. Am Fam Physician. 2005 Oct 1;72(7):1243-50.</citation>
    <PMID>16225027</PMID>
  </reference>
  <reference>
    <citation>Wang X, Chen C, Wang L, Chen D, Guang W, French J. Conception, early pregnancy loss, and time to clinical pregnancy: a population-based prospective study. Fertil Steril. 2003 Mar;79(3):577-84. doi: 10.1016/s0015-0282(02)04694-0.</citation>
    <PMID>12620443</PMID>
  </reference>
  <reference>
    <citation>Sellmyer MA, Desser TS, Maturen KE, Jeffrey RB Jr, Kamaya A. Physiologic, histologic, and imaging features of retained products of conception. Radiographics. 2013 May;33(3):781-96. doi: 10.1148/rg.333125177.</citation>
    <PMID>23674774</PMID>
  </reference>
  <reference>
    <citation>Casikar I, Lu C, Oates J, Bignardi T, Alhamdan D, Condous G. The use of power Doppler colour scoring to predict successful expectant management in women with an incomplete miscarriage. Hum Reprod. 2012 Mar;27(3):669-75. doi: 10.1093/humrep/der433. Epub 2012 Jan 9.</citation>
    <PMID>22232130</PMID>
  </reference>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>July 24, 2017</study_first_submitted>
  <study_first_submitted_qc>July 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 26, 2017</study_first_posted>
  <last_update_submitted>August 6, 2017</last_update_submitted>
  <last_update_submitted_qc>August 6, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 8, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Meir Medical Center</investigator_affiliation>
    <investigator_full_name>Anat Hershko Klement</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>incomplete abortion</keyword>
  <keyword>retained products of conception</keyword>
  <keyword>combined oral contraceptives</keyword>
  <keyword>ultrasound</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Contraceptive Agents</mesh_term>
    <mesh_term>Contraceptives, Oral</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/NCT03230825
org study id: 0263-16
nct id: NCT03230825
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
We speculate that the use of combined oral contraceptives may be a possible solution to
      promote the management of retained pregnancy products versus expectant management. By
      withdrawing the pill, the endometrium is expected to shed in a synchronized fashion (estrogen
      and progestin withdrawal bleeding and may also shed the retained products of conception and
      avoid a surgical procedure with its related potential complications.
Miscarriage is a common event in general gynaecological practice, and is an age-dependent
      outcome. It is estimated -that approximately 20 percent of clinically recognized pregnancies
      will result in a miscarriage, and the prevalence is much higher if preclinical pregnancies
      are included as well .Failure to pass the contents of the pregnancy is reported in 15% of
      patients going through a spontaneous 1st trimester miscarriage and a similar rate in patients
      going through an induced medical abortion after a spontaneous pregnancy loss (miscarriage)
      and planned pregnancy termination using PGE1 (MisWe speculate that the use of combined oral
      contraceptives may be a possible solution to promote the management of retained pregnancy
      products versus expectant management. The exposure to combined oral contraceptives is known
      to induce secretory and decidual changes in the endometrium .By withdrawing the pill, the
      endometrium is expected to shed in a synchronized fashion (estrogen and progestin withdrawal
      bleeding). We hypothesize that such withdrawal bleeding may also shed the retained products
      of conception and avoid a surgical procedure with its related potential complications.
      oprostol).

      All patients diagnosed with RPOC according to the inclusion and exclusion criteria , will be
      asked to give their informed consent to take part in the study.

      Once informed consent forms are signed, the patient will be randomized (using a randomization
      table handled by a 3rd party) into one of 2 groups:

        1. Expectant management of 3 weeks and a follow up visit a week after.

        2. Oral contraceptive agent, given for free, for 3 weeks and a follow up visit a week after
           treatment withdrawal.

      We wish to emphasize that the current management in our ward is expectant management in the
      population eligible for this study.

      All US scans will be performed by 2 qualified sonographers using a 7.5 MHz transvaginal
      transducer. 2D images in both sagittal and axial planes will be obtained. Sonographic
      features to be evaluated are: endometrial maximal thickness measured in the sagittal plan,
      presence or absence and size of an endometrial mass (3 dimensions) and grading of endometrial
      vascularity. Vascularity will be graded as type 0, 1, 2 or 3 defining no detectable, minimal
      (less then myometrium), moderate (nearly equal to myometrium) or marked vascularity
      respectively (4).

      At enrollment the patient will be monitored and interviewed for the following variables :

      Age, BMI, OB - GYN history, smoking status, Blood pressure, pulse rate,Temperature, blood
      count, HCG levels.

      All patients will be invited to a follow up visit 3 weeks after randomization. The follow up
      visit will include again an ultrasound scan as described above.

      In any case the patient is reporting a menstrual bleeding/ abdominal pain/ fever she will
      contact the 24hr available ER of the ward and will be evaluated for complications. After
      evaluation is completed the principal investigator will be contacted and the case will be
      discussed as for the need for additional measures and documented in the research file.

      In the planned 4 week post randomization visit the following parameters will be monitored:

      Blood pressure, pulse rate, Temperature, blood count, HCG levels as well as a review of any
      symptoms.

      Following the interview a trans-vaginal scan will be performed in order to evaluate the
      cavity and any retained products existence and any presence of blood flow in case of a
      positive diagnosis.

      In any case of retained products detected by ultrasound we will recommend a surgical
      hysteroscopy.

      The oral contraceptives will be donated by DEXCEL LTD, ISRAEL to the hospital pharmacy, where
      it will be stored.

      Brand name :FLAME containing 0.02 mg Ethinylestradiol and 0.075 mg Gestodene. Israeli
      authorities demand that a drug which is tested in a research will be provided to the
      participant without charging.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Once informed consent forms are signed, the patient will be randomized (using a randomization table handled by a 3rd party) into one of 2 groups:
Expectant management of 3 weeks and a follow up visit a week after.
Oral contraceptive agent, given for free, for 3 weeks and a follow up visit a week after treatment withdrawal.
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: Data analysis will be performed according to group code .
measure: persistent retained pregnancy products rate
time frame: 4 weeks
description: rate
arm group label: Oral contraceptives
arm group type: Experimental
description: Oral contraceptive agent, given for free, for 3 weeks and a follow up visit a week after treatment withdrawal.
arm group label: Expectant management
arm group type: Sham Comparator
description: Expectant management for 3 weeks and a follow up visit a week later.
intervention type: Drug
intervention name: Oral contraceptive
description: Daily oral contraceptive agent for 3 weeks (FLAME, containing 0.02 mg Ethinylestradiol and 0.075 mg Gestodene)
arm group label: Oral contraceptives
intervention type: Other
intervention name: Expectant management
description: No intervention and a follow up visit a wewk later
arm group label: Expectant management
criteria: 
gender: Female
gender based: Yes
gender description: Retaiend pregnancy products
minimum age: 16 Years
maximum age: 54 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Anat Hershko Klement, MD
role: Principal Investigator
affiliation: Meir Medical Center
last name: Anat Hershko Klement, MD
phone: +972549170084
email: anat.klement@gmail.com
citation: Chen BA, Creinin MD. Medical management of early pregnancy failure: efficacy. Semin Reprod Med. 2008 Sep;26(5):411-22. doi: 10.1055/s-0028-1087107. Epub 2008 Sep 29.
PMID: 18825609
citation: Griebel CP, Halvorsen J, Golemon TB, Day AA. Management of spontaneous abortion. Am Fam Physician. 2005 Oct 1;72(7):1243-50.
PMID: 16225027
citation: Wang X, Chen C, Wang L, Chen D, Guang W, French J. Conception, early pregnancy loss, and time to clinical pregnancy: a population-based prospective study. Fertil Steril. 2003 Mar;79(3):577-84. doi: 10.1016/s0015-0282(02)04694-0.
PMID: 12620443
citation: Sellmyer MA, Desser TS, Maturen KE, Jeffrey RB Jr, Kamaya A. Physiologic, histologic, and imaging features of retained products of conception. Radiographics. 2013 May;33(3):781-96. doi: 10.1148/rg.333125177.
PMID: 23674774
citation: Casikar I, Lu C, Oates J, Bignardi T, Alhamdan D, Condous G. The use of power Doppler colour scoring to predict successful expectant management in women with an incomplete miscarriage. Hum Reprod. 2012 Mar;27(3):669-75. doi: 10.1093/humrep/der433. Epub 2012 Jan 9.
PMID: 22232130
responsible party type: Principal Investigator
investigator affiliation: Meir Medical Center
investigator full name: Anat Hershko Klement
investigator title: Principal Investigator
mesh term: Contraceptive Agents
mesh term: Contraceptives, Oral
sharing ipd: No