<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/NCT02237755</url>
  </required_header>
  <id_info>
    <org_study_id>NV25042014</org_study_id>
    <nct_id>NCT02237755</nct_id>
  </id_info>
  <brief_title>Clomiphene Citrate in Combination With Gonadotropins for Ovarian Stimulation in Women With Poor Ovarian Response.</brief_title>
  <official_title>Prospective Randomized Trial on the Effect of Clomiphene Citrate Administration in Women With Poor Ovarian Reserve Undergoing Controlled Ovarian Stimulation for IVF. Impact on Stimulation Characteristics and Pregnancy Outcome.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Athens</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Lito Maternity Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Athens</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Coadministration of various drugs used for ovarian stimulation can increase the efficiency of&#xD;
      IVF especially in poor responders. The investigators hypothesize that ovarian response of&#xD;
      those patients could improve by using combination of clomiphene citrate with gonadotropins in&#xD;
      infertile women with poor response to gonadotrophin administration only.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients diagnosed with poor ovarian response will be included in the study. The definition&#xD;
      of poor response was based on the presence of at least one of the following criteria: Age &gt;&#xD;
      40 years old, day 2 FSH &gt;9.5 mIU/ml, AMH &lt; 2ng/ml ,at least one previous COH with less than 3&#xD;
      oocytes retrieved, at least one cancelled attempt due to poor response, estradiol less than&#xD;
      500 pg/ml on the day of HCG. All patients will be counseled regarding their prognosis and&#xD;
      other treatment options including oocyte donation as well as adoption were also presented and&#xD;
      discussed in detail. Early follicular phase FSH, estradiol (E2) and Anti-Mullerian Hormone&#xD;
      (AMH) will be measured prior to the initiation of treatment. Women in the Clomiphene group&#xD;
      will receive 100-150 mg of Clomiphene citrate once per day for 5 days in combination with&#xD;
      gonadotropins according to short GnRH-antagonist protocol: all women will have measurements&#xD;
      of serum FSH and estradiol and a pelvic sonogram on the second day of their cycle. Providing&#xD;
      that serum FSH is &lt; 17 mIU/ml and estradiol is &lt; 70 pg/ml on day 2 , ovarian stimulation will&#xD;
      be initiated with 100-150 mg of Clomiphene citrate in combination with 450 IU of&#xD;
      gonadotropins either in the form of a combination of highly purified urinary FSH and LH or&#xD;
      with a combination of Rec FSH and Rec LH. All patients will be re-evaluated on day 5 of the&#xD;
      stimulation, and dosage adjustments will be made and the antagonists (Cetrorelix or ganirelix&#xD;
      0.25 mg/day) will be initiated. When at least 2 follicles reach an average diameter of 17 mm,&#xD;
      final oocyte maturation will be triggered with 10,000IU of hCG ( Pregnyl, Organon, Greece&#xD;
      Inc.). Oocyte retrieval will be performed 34 to 36 hours later. All patients will undergo&#xD;
      ICSI. Patients with successful fertilization will have embryo transfer under sonographic&#xD;
      guidance on day 3 after retrieval. Women in the Gonadotropin group will receive only&#xD;
      gonadotropins according to short GnRH-antagonist protocol as it was mentioned above.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>October 2014</start_date>
  <completion_date type="Anticipated">December 2015</completion_date>
  <primary_completion_date type="Anticipated">November 2014</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical pregnancy</measure>
    <time_frame>14 days after embryo transfer</time_frame>
    <description>At the completion of the ovarian stimulation patients that will proceed to transfer and have a positive pregnancy test will have sonographic evaluation for confirmation of clinical pregnancy.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Female Infertility</condition>
  <arm_group>
    <arm_group_label>Clomiphene citrate</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Administration of Clomiphene citrate in combination with gonadotropins according to a short stimulation GnRH antagonists protocol.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Gonadotropins</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients in this group will be stimulated according to a short stimulation protocol with gonadotropins and GnRH antagonists.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clomiphene citrate</intervention_name>
    <description>clomiphene citrate 100mg/day will be added to the standard gonadotropin regiment</description>
    <arm_group_label>Clomiphene citrate</arm_group_label>
    <arm_group_label>Gonadotropins</arm_group_label>
    <other_name>Clomiphene citrate 50 mg/tab</other_name>
    <other_name>Cerpafar 50 mg/tab</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gonadotropins</intervention_name>
    <description>All patients will be stimulated with a fixed GnRH-antagonist protocol. Ovarian stimulation will be initiated with 450 IU of gonadotropins either in the form of a combination of highly purified urinary FSH and LH or with a combination of Rec FSH and Rec LH.</description>
    <arm_group_label>Clomiphene citrate</arm_group_label>
    <arm_group_label>Gonadotropins</arm_group_label>
    <other_name>Menopur 75IU , Gonal</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women with poor response to ovarian stimulation. The definition of poor response was&#xD;
             based on the presence of at least one of the following criteria: Age &gt; 40 years old,&#xD;
             day 2 FSH &gt;9.5 mIU/ml, AMH &lt; 2ng/ml ,at least one previous COH with less than 3&#xD;
             oocytes retrieved, at least one cancelled attempt due to poor response, estradiol less&#xD;
             than 500 pg/ml on the day of HCG.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  All other women that do not fulfill the above mentioned criteria&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nikos Vlahos, Assoc. Prof.</last_name>
    <role>Study Chair</role>
    <affiliation>University of Athens, 2nd Department of Obstetrics and Gynecology</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Olga Triantafyllidou, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Athens School of Medicine</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Nikos Vlahos, MD</last_name>
    <phone>30 210 7286000</phone>
    <email>nikosvlahos@med.uoa.gr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Olga Triantafyllidou, MD</last_name>
    <phone>30 2107485591</phone>
    <email>triantafyllidouolga@yahoo.com</email>
  </overall_contact_backup>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 9, 2014</study_first_submitted>
  <study_first_submitted_qc>September 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2014</study_first_posted>
  <last_update_submitted>September 9, 2014</last_update_submitted>
  <last_update_submitted_qc>September 9, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 11, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Athens</investigator_affiliation>
    <investigator_full_name>Nikos Vlahos</investigator_full_name>
    <investigator_title>Associate Professor of Obstetrics and Gynecology</investigator_title>
  </responsible_party>
  <keyword>Clomiphene citrate</keyword>
  <keyword>IVF</keyword>
  <keyword>Pregnancy Rates</keyword>
  <keyword>Ovarian Reserve</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infertility</mesh_term>
    <mesh_term>Infertility, Female</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Citric Acid</mesh_term>
    <mesh_term>Sodium Citrate</mesh_term>
    <mesh_term>Clomiphene</mesh_term>
    <mesh_term>Enclomiphene</mesh_term>
    <mesh_term>Zuclomiphene</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/NCT02237755
org study id: NV25042014
nct id: NCT02237755
lead sponsor: 
collaborator: 
has dmc: Yes
Coadministration of various drugs used for ovarian stimulation can increase the efficiency of
      IVF especially in poor responders. The investigators hypothesize that ovarian response of
      those patients could improve by using combination of clomiphene citrate with gonadotropins in
      infertile women with poor response to gonadotrophin administration only.
Patients diagnosed with poor ovarian response will be included in the study. The definition
      of poor response was based on the presence of at least one of the following criteria: Age >
      40 years old, day 2 FSH >9.5 mIU/ml, AMH < 2ng/ml ,at least one previous COH with less than 3
      oocytes retrieved, at least one cancelled attempt due to poor response, estradiol less than
      500 pg/ml on the day of HCG. All patients will be counseled regarding their prognosis and
      other treatment options including oocyte donation as well as adoption were also presented and
      discussed in detail. Early follicular phase FSH, estradiol (E2) and Anti-Mullerian Hormone
      (AMH) will be measured prior to the initiation of treatment. Women in the Clomiphene group
      will receive 100-150 mg of Clomiphene citrate once per day for 5 days in combination with
      gonadotropins according to short GnRH-antagonist protocol: all women will have measurements
      of serum FSH and estradiol and a pelvic sonogram on the second day of their cycle. Providing
      that serum FSH is < 17 mIU/ml and estradiol is < 70 pg/ml on day 2 , ovarian stimulation will
      be initiated with 100-150 mg of Clomiphene citrate in combination with 450 IU of
      gonadotropins either in the form of a combination of highly purified urinary FSH and LH or
      with a combination of Rec FSH and Rec LH. All patients will be re-evaluated on day 5 of the
      stimulation, and dosage adjustments will be made and the antagonists (Cetrorelix or ganirelix
      0.25 mg/day) will be initiated. When at least 2 follicles reach an average diameter of 17 mm,
      final oocyte maturation will be triggered with 10,000IU of hCG ( Pregnyl, Organon, Greece
      Inc.). Oocyte retrieval will be performed 34 to 36 hours later. All patients will undergo
      ICSI. Patients with successful fertilization will have embryo transfer under sonographic
      guidance on day 3 after retrieval. Women in the Gonadotropin group will receive only
      gonadotropins according to short GnRH-antagonist protocol as it was mentioned above.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Clinical pregnancy
time frame: 14 days after embryo transfer
description: At the completion of the ovarian stimulation patients that will proceed to transfer and have a positive pregnancy test will have sonographic evaluation for confirmation of clinical pregnancy.
arm group label: Clomiphene citrate
arm group type: Active Comparator
description: Administration of Clomiphene citrate in combination with gonadotropins according to a short stimulation GnRH antagonists protocol.
arm group label: Gonadotropins
arm group type: Active Comparator
description: Patients in this group will be stimulated according to a short stimulation protocol with gonadotropins and GnRH antagonists.
intervention type: Drug
intervention name: Clomiphene citrate
description: clomiphene citrate 100mg/day will be added to the standard gonadotropin regiment
arm group label: Clomiphene citrate
arm group label: Gonadotropins
other name: Clomiphene citrate 50 mg/tab
other name: Cerpafar 50 mg/tab
intervention type: Drug
intervention name: Gonadotropins
description: All patients will be stimulated with a fixed GnRH-antagonist protocol. Ovarian stimulation will be initiated with 450 IU of gonadotropins either in the form of a combination of highly purified urinary FSH and LH or with a combination of Rec FSH and Rec LH.
arm group label: Clomiphene citrate
arm group label: Gonadotropins
other name: Menopur 75IU , Gonal
criteria: 
gender: Female
minimum age: 20 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Nikos Vlahos, Assoc. Prof.
role: Study Chair
affiliation: University of Athens, 2nd Department of Obstetrics and Gynecology
last name: Olga Triantafyllidou, MD
role: Principal Investigator
affiliation: University of Athens School of Medicine
last name: Nikos Vlahos, MD
phone: 30 210 7286000
email: nikosvlahos@med.uoa.gr
last name: Olga Triantafyllidou, MD
phone: 30 2107485591
email: triantafyllidouolga@yahoo.com
responsible party type: Principal Investigator
investigator affiliation: University of Athens
investigator full name: Nikos Vlahos
investigator title: Associate Professor of Obstetrics and Gynecology
mesh term: Infertility
mesh term: Infertility, Female
mesh term: Citric Acid
mesh term: Sodium Citrate
mesh term: Clomiphene
mesh term: Enclomiphene
mesh term: Zuclomiphene