<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/NCT01679574</url>
  </required_header>
  <id_info>
    <org_study_id>pcolcm</org_study_id>
    <nct_id>NCT01679574</nct_id>
  </id_info>
  <brief_title>Letrozole or Combined Clomiphene Citrate Metformin as a First Line Treatment in Women With Polycystic Ovarian Syndrome</brief_title>
  <acronym>PCO</acronym>
  <official_title>Letrozole Versus Clomiphene Citrate Plus Metformin in the First Treatment of Infertility in Patients With Polycystic Ovarian Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assiut University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assiut University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to compare and determine the efficacy of letrozole&#xD;
      administration to that of combined metformin and Clomiphene in infertile women with&#xD;
      polycystic ovary syndrome (PCOS) not treated before with any ovulation induction agent&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will be in 200 patient diagnosed to have PCOS among those attending the Fertility&#xD;
      Outpatient Clinic at the Women's Health Center, Assiut University Hospitals.&#xD;
&#xD;
      The present study was prospective randomized controlled trial conducted over a period of 3&#xD;
      years from 1st of January 2009 to 1st of January 2012, at the Women's Health Center, Assiut&#xD;
      University hospital, Assiut, Egypt, after approval was received from the Ethics Committee of&#xD;
      faculty of medicine , Assiut University. Women referred to the infertility clinic in women's&#xD;
      health center were screened for PCO using Rotterdam consensus criteria for the diagnosis of&#xD;
      PCOS. The patients who were newly diagnosed as PCO and not treated previously were invited to&#xD;
      participate in our study. Written informed consent was obtained from each participant after&#xD;
      an information sheet had been provided. The patients had the right to refuse participation in&#xD;
      the study or to withdraw at any time without being denied their full regular clinical care.&#xD;
      All personal information and medical data were confidential and were not made available to&#xD;
      third parties. All participants met the Rotterdam consensus criteria for the diagnosis of&#xD;
      PCOS. At admission, a thorough medical history was taken and all women underwent physical&#xD;
      examination, which included anthropometric measurements and after spontaneous menstruation or&#xD;
      progestin induced withdrawal bleeding, basal endocrine evaluation on day 3 of the cycle&#xD;
      included measurement of the serum concentrations of luteinizing hormone (LH),&#xD;
      follicle-stimulating hormone (FSH),thyroid stimulating hormone(TSH ) and prolactin. Then&#xD;
      vaginal sonographic examination were done to measure endometrial thickness and exclude cases&#xD;
      endometrial pathology or baseline ovarian cysts.&#xD;
&#xD;
      The participants were randomized to receive letrozole or clomiphene citrate plus metformin.&#xD;
      Randomization was performed using a computer-generated random numbers table, and allocation&#xD;
      concealment was achieved using serially numbered opaque envelopes that were only opened once&#xD;
      the interventions were assigned.&#xD;
&#xD;
      In the letrozole group, the ovaries were stimulated using 2.5mg/day letrozole (Femara;&#xD;
      Novartis Pharma, Basel, Switzerland) for 5 days,in the form of one tablet( 2.5 mg) per day&#xD;
      for 5 days from day 3 to day 7 of the menstrual cycle and if ovulation has occurred with no&#xD;
      pregnancy continue on the same dose for another 2 consecutive cycles ,but if no ovulation&#xD;
      increase the dose to 2 tablets per day(5 mg) for another 2 consecutive cycles in the same&#xD;
      manner .&#xD;
&#xD;
      The patients in the second group will take metformin (Cidophage tablets,500 mg per tablet;&#xD;
      CID, ARE, in an oral dose of 1,500 mg/d) 500mg three times daily for 3 months Plus&#xD;
      clomid(50-mg tablets twice daily; Global Napi Pharmaceuticals, Cairo, Egypt , Arab Republic&#xD;
      of Egypt) In the form of 50 mg twice daily (100mg /day) for 5 days from day 3 to day 7 of&#xD;
      menstrual cycle and to be repeated for 3 consecutive cycles in the same manner if no&#xD;
      pregnancy occur.&#xD;
&#xD;
      In both groups, endometrial thickness and mean follicular diameter were assessed by the same&#xD;
      investigator using transvaginal ultrasound on days 2 ,10, 12, and 14 of the menstrual cycle,&#xD;
      and 10 000 IU of human chorionic gonadotropin (hCG) (Pregnyl; Organon, Oss, The Netherlands)&#xD;
      were injected intramuscularly if there was at least 1 leading follicle measuring 18 mm or&#xD;
      more in diameter and endometrial thickness detected at that time(endometrial thickness was&#xD;
      determined at the greatest diameter perpendicular to the midsagittal plane in the fundal&#xD;
      region, including both layers of the endometrium). All participants were advised to have&#xD;
      intercourse 24-36 hours after the hCG injection. Two days after being given Human chorionic&#xD;
      gonadotropin, the patients were assessed for signs of ovulation (disappearance of&#xD;
      preovulatory follicle, fluid in the cul-de-sac, and/or corpus luteum formation). Pregnancy&#xD;
      will be diagnosed when positive pregnancy test in urine done or a gestational sac was&#xD;
      detected on transvaginal ultrasound examination 1week after the missed period or serum β-hCG&#xD;
      concentration 14 days after HCG injection if menses had not occurred. A biochemical pregnancy&#xD;
      was considered when the serum β-hCG concentration was 50 mIU/mL or more in the absence of&#xD;
      menstruation. All study medication were stopped when there was positive pregnancy&#xD;
      test.Pregnant patients then will be followed up until an ultrasound could document the&#xD;
      viability of pregnancy. A clinical pregnancy was defined as the presence of a gestational sac&#xD;
      with a beating fetal heart on transvaginal ultrasound. A spontaneous abortion was defined as&#xD;
      the spontaneous loss of a pregnancy before the end of the 20th week.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2009</start_date>
  <completion_date type="Actual">January 2012</completion_date>
  <primary_completion_date type="Actual">January 2012</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>ovulation rate</measure>
    <time_frame>3 years</time_frame>
    <description>Principally the ovulation rate as well as the number of growing and mature follicles and endometrial thickness (mm).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The occurrence of pregnancy and miscarriage</measure>
    <time_frame>3 years</time_frame>
    <description>The occurrence of pregnancy and miscarriage</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">200</enrollment>
  <condition>Polycystic Ovary Syndrome</condition>
  <arm_group>
    <arm_group_label>letrozole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Letrozole tablets (Femara; Novartis Pharma, Switzerland) 2.5 mg letrozole daily from day 3 of the menses for 5 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Metformin and clomiphene</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>.Drug: metformin (Cidophage®; CID,Cairo, Egypt) metformin 1500 daily for 3 months&#xD;
Drug: CC (Clomid®; Global Napi Pharmaceuticals, Cairo, Egypt) 100 mg CC for 5 days starting from day 3 of menstruation</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Letrozole</intervention_name>
    <description>•Drug: Letrozole tablets (Femara; Novartis Pharma, Switzerland) 2.5 mg letrozole daily from day 3 of the menses for 5 days</description>
    <arm_group_label>letrozole</arm_group_label>
    <other_name>Femara; Novartis Pharma, Switzerland</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clomiphene</intervention_name>
    <description>•Drug: CC (Clomid®; Global Napi Pharmaceuticals, Cairo, Egypt) 100 mg CC for 5 days starting from day 3 of menstruation</description>
    <arm_group_label>Metformin and clomiphene</arm_group_label>
    <other_name>clomid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>•Drug: metformin HCl (Cidophage®; CID,Cairo, Egypt) metformin HCl 1500 daily for 3 months</description>
    <arm_group_label>Metformin and clomiphene</arm_group_label>
    <other_name>Cidophage</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All participants met the Rotterdam consensus criteria for the diagnosis of PCOS .&#xD;
             .Primary infertility because of anovulation for at least 1 year.&#xD;
&#xD;
          -  Only fresh (not treated previously) cases were recruited. .The male partner of each&#xD;
             participant was required to have a normal result on semen analysis&#xD;
             (count&gt;20million/ml,motility&gt;40%and normal morphology &gt;30%).&#xD;
&#xD;
          -  Each woman was required to have patent tubes on hysterosalpingography or on a&#xD;
             diagnostic laparoscopy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age below 18 years or above 35 years , trial of ovulation induction prior to the stud&#xD;
             ,BMI &gt;35 .&#xD;
&#xD;
          -  Presence of other causes of infertility; hyperprolactinemia (morning plasma prolactin&#xD;
             concentration 30 ng/mL or more); any other endocrine, hepatic, or renal disorder;&#xD;
             presence of an organic pelvic mass;&#xD;
&#xD;
          -  History of abdominal surgery that might have caused pelvic factor infertility.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tarek al Hussaini, prof</last_name>
    <role>Study Chair</role>
    <affiliation>Assiut University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Safowt Abd El Rady, Prof</last_name>
    <role>Study Director</role>
    <affiliation>Assiut university hosiptal</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mohamad S Abd Allah, Ass prof</last_name>
    <role>Study Director</role>
    <affiliation>assiut university hosital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Assiut University</name>
      <address>
        <city>Assiut</city>
        <zip>11111</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>September 2012</verification_date>
  <study_first_submitted>August 31, 2012</study_first_submitted>
  <study_first_submitted_qc>September 3, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 6, 2012</study_first_posted>
  <last_update_submitted>September 6, 2012</last_update_submitted>
  <last_update_submitted_qc>September 6, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 7, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Assiut University</investigator_affiliation>
    <investigator_full_name>ahmed ali</investigator_full_name>
    <investigator_title>Prinicple investigator</investigator_title>
  </responsible_party>
  <keyword>PCO</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Polycystic Ovary Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
    <mesh_term>Letrozole</mesh_term>
    <mesh_term>Clomiphene</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/NCT01679574
org study id: pcolcm
nct id: NCT01679574
lead sponsor: 
has dmc: No
The purpose of this study is to compare and determine the efficacy of letrozole
      administration to that of combined metformin and Clomiphene in infertile women with
      polycystic ovary syndrome (PCOS) not treated before with any ovulation induction agent
The study will be in 200 patient diagnosed to have PCOS among those attending the Fertility
      Outpatient Clinic at the Women's Health Center, Assiut University Hospitals.

      The present study was prospective randomized controlled trial conducted over a period of 3
      years from 1st of January 2009 to 1st of January 2012, at the Women's Health Center, Assiut
      University hospital, Assiut, Egypt, after approval was received from the Ethics Committee of
      faculty of medicine , Assiut University. Women referred to the infertility clinic in women's
      health center were screened for PCO using Rotterdam consensus criteria for the diagnosis of
      PCOS. The patients who were newly diagnosed as PCO and not treated previously were invited to
      participate in our study. Written informed consent was obtained from each participant after
      an information sheet had been provided. The patients had the right to refuse participation in
      the study or to withdraw at any time without being denied their full regular clinical care.
      All personal information and medical data were confidential and were not made available to
      third parties. All participants met the Rotterdam consensus criteria for the diagnosis of
      PCOS. At admission, a thorough medical history was taken and all women underwent physical
      examination, which included anthropometric measurements and after spontaneous menstruation or
      progestin induced withdrawal bleeding, basal endocrine evaluation on day 3 of the cycle
      included measurement of the serum concentrations of luteinizing hormone (LH),
      follicle-stimulating hormone (FSH),thyroid stimulating hormone(TSH ) and prolactin. Then
      vaginal sonographic examination were done to measure endometrial thickness and exclude cases
      endometrial pathology or baseline ovarian cysts.

      The participants were randomized to receive letrozole or clomiphene citrate plus metformin.
      Randomization was performed using a computer-generated random numbers table, and allocation
      concealment was achieved using serially numbered opaque envelopes that were only opened once
      the interventions were assigned.

      In the letrozole group, the ovaries were stimulated using 2.5mg/day letrozole (Femara;
      Novartis Pharma, Basel, Switzerland) for 5 days,in the form of one tablet( 2.5 mg) per day
      for 5 days from day 3 to day 7 of the menstrual cycle and if ovulation has occurred with no
      pregnancy continue on the same dose for another 2 consecutive cycles ,but if no ovulation
      increase the dose to 2 tablets per day(5 mg) for another 2 consecutive cycles in the same
      manner .

      The patients in the second group will take metformin (Cidophage tablets,500 mg per tablet;
      CID, ARE, in an oral dose of 1,500 mg/d) 500mg three times daily for 3 months Plus
      clomid(50-mg tablets twice daily; Global Napi Pharmaceuticals, Cairo, Egypt , Arab Republic
      of Egypt) In the form of 50 mg twice daily (100mg /day) for 5 days from day 3 to day 7 of
      menstrual cycle and to be repeated for 3 consecutive cycles in the same manner if no
      pregnancy occur.

      In both groups, endometrial thickness and mean follicular diameter were assessed by the same
      investigator using transvaginal ultrasound on days 2 ,10, 12, and 14 of the menstrual cycle,
      and 10 000 IU of human chorionic gonadotropin (hCG) (Pregnyl; Organon, Oss, The Netherlands)
      were injected intramuscularly if there was at least 1 leading follicle measuring 18 mm or
      more in diameter and endometrial thickness detected at that time(endometrial thickness was
      determined at the greatest diameter perpendicular to the midsagittal plane in the fundal
      region, including both layers of the endometrium). All participants were advised to have
      intercourse 24-36 hours after the hCG injection. Two days after being given Human chorionic
      gonadotropin, the patients were assessed for signs of ovulation (disappearance of
      preovulatory follicle, fluid in the cul-de-sac, and/or corpus luteum formation). Pregnancy
      will be diagnosed when positive pregnancy test in urine done or a gestational sac was
      detected on transvaginal ultrasound examination 1week after the missed period or serum β-hCG
      concentration 14 days after HCG injection if menses had not occurred. A biochemical pregnancy
      was considered when the serum β-hCG concentration was 50 mIU/mL or more in the absence of
      menstruation. All study medication were stopped when there was positive pregnancy
      test.Pregnant patients then will be followed up until an ultrasound could document the
      viability of pregnancy. A clinical pregnancy was defined as the presence of a gestational sac
      with a beating fetal heart on transvaginal ultrasound. A spontaneous abortion was defined as
      the spontaneous loss of a pregnancy before the end of the 20th week.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: ovulation rate
time frame: 3 years
description: Principally the ovulation rate as well as the number of growing and mature follicles and endometrial thickness (mm).
measure: The occurrence of pregnancy and miscarriage
time frame: 3 years
description: The occurrence of pregnancy and miscarriage
arm group label: letrozole
arm group type: Experimental
description: Letrozole tablets (Femara; Novartis Pharma, Switzerland) 2.5 mg letrozole daily from day 3 of the menses for 5 days
arm group label: Metformin and clomiphene
arm group type: Active Comparator
description: .Drug: metformin (Cidophage®; CID,Cairo, Egypt) metformin 1500 daily for 3 months
Drug: CC (Clomid®; Global Napi Pharmaceuticals, Cairo, Egypt) 100 mg CC for 5 days starting from day 3 of menstruation
intervention type: Drug
intervention name: Letrozole
description: •Drug: Letrozole tablets (Femara; Novartis Pharma, Switzerland) 2.5 mg letrozole daily from day 3 of the menses for 5 days
arm group label: letrozole
other name: Femara; Novartis Pharma, Switzerland
intervention type: Drug
intervention name: Clomiphene
description: •Drug: CC (Clomid®; Global Napi Pharmaceuticals, Cairo, Egypt) 100 mg CC for 5 days starting from day 3 of menstruation
arm group label: Metformin and clomiphene
other name: clomid
intervention type: Drug
intervention name: Metformin
description: •Drug: metformin HCl (Cidophage®; CID,Cairo, Egypt) metformin HCl 1500 daily for 3 months
arm group label: Metformin and clomiphene
other name: Cidophage
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 35 Years
healthy volunteers: No
last name: Tarek al Hussaini, prof
role: Study Chair
affiliation: Assiut University
last name: Safowt Abd El Rady, Prof
role: Study Director
affiliation: Assiut university hosiptal
last name: Mohamad S Abd Allah, Ass prof
role: Study Director
affiliation: assiut university hosital
facility: 
country: Egypt
responsible party type: Principal Investigator
investigator affiliation: Assiut University
investigator full name: ahmed ali
investigator title: Prinicple investigator
mesh term: Polycystic Ovary Syndrome
mesh term: Syndrome
mesh term: Metformin
mesh term: Letrozole
mesh term: Clomiphene