<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/NCT02264743</url>
  </required_header>
  <id_info>
    <org_study_id>2013MM002B</org_study_id>
    <secondary_id>2013-002094-22</secondary_id>
    <nct_id>NCT02264743</nct_id>
  </id_info>
  <brief_title>Oral Verses Patch Trial In Menopausal Women - Individualisation of Oestrogen Therapy</brief_title>
  <acronym>OPTIMISE</acronym>
  <official_title>Comparison of Ultra-low-dose Oral Versus Trans-dermal Hormone Therapy on Coagulation Activation and Metabolic Risk Factors for Cardiovascular Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Royal Brompton &amp; Harefield NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Chelsea and Westminster NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Imperial College Healthcare NHS Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Royal Brompton &amp; Harefield NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Ultra-low-dose oral E2/D will have more beneficial effects than trans-dermal HRT on lipids&#xD;
      and insulin resistance in postmenopausal women, whilst adverse effects on coagulation will be&#xD;
      avoided.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Following screening for eligibility, women will be studied at baseline and then randomized to&#xD;
      one of two groups:&#xD;
&#xD;
      Group A administered Femoston Conti - oral oestradiol 17β 0.5 mg/dydrogesterone 2.5 mg daily&#xD;
      for the duration of the treatment phase (24 weeks)&#xD;
&#xD;
      Group B administered ½ Evorel Conti patches - trans-dermal Estradiol 25 mcg/norethisterone&#xD;
      acetate 85 mcg (½ Evorel Conti patches) daily for the duration of the treatment phase (24&#xD;
      weeks).&#xD;
&#xD;
      Studies will be repeated after 6 months of therapy at the follow up visit.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>November 2013</start_date>
  <completion_date type="Anticipated">November 2015</completion_date>
  <primary_completion_date type="Anticipated">November 2014</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>Thrombin Generation IU/DL</measure>
    <time_frame>Six months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>triglycerides</measure>
    <time_frame>6 months</time_frame>
    <description>mmol/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HDL</measure>
    <time_frame>6 months</time_frame>
    <description>mmol/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total cholesterol</measure>
    <time_frame>6 months</time_frame>
    <description>mmol/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>LDL</measure>
    <time_frame>6 months</time_frame>
    <description>mmol/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>D-Dimers</measure>
    <time_frame>6 months</time_frame>
    <description>ng/ml</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>APC resistance</measure>
    <time_frame>6 months</time_frame>
    <description>&gt;2 or &lt;2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fibrinogen</measure>
    <time_frame>6 months</time_frame>
    <description>g/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Factor V11</measure>
    <time_frame>6 months</time_frame>
    <description>U/ml</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PAI-1 protein</measure>
    <time_frame>6 months</time_frame>
    <description>nq/ml</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fasting insulin</measure>
    <time_frame>6 months</time_frame>
    <description>pmol/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fasting glucose</measure>
    <time_frame>6 months</time_frame>
    <description>mmol/L</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Venous Thrombosis</condition>
  <condition>Insulin Resistance</condition>
  <arm_group>
    <arm_group_label>Femoston Conti 0.5mg/2.5mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ultra low dose, film-coated 17β-estradiol (as hemihydrate) 0.5mg &amp; dydrogesterone 2.5 mg&#xD;
Once a day&#xD;
The duration is six months.&#xD;
Drug intervention: Estradiol&amp;DydrogesteronevsOestradiol&amp;Norethisterone acetate</description>
  </arm_group>
  <arm_group>
    <arm_group_label>EVOREL® CONTI transdermal patches</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>EVOREL CONTI is a transdermal self adhesive patch which is 0.1 mm in thickness and each patch releases 50mcg of oestradiol and 170mcg of norethisterone acetate over 24 hours .&#xD;
The Evorel Conti patch is cut in half and applied to the lower part of the body for 3.5 days (delivering approx 25mcg of oestradiol over 24 hours ) this is replaced every 3.5 days .&#xD;
The duration is six months.&#xD;
Drug intervention: Estradiol&amp;DydrogesteronevsOestradiol&amp;Norethisterone acetate</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Femoston Conti</intervention_name>
    <description>Ultra-low-dose oral E2/D [Oestradiol 17β 0.5mg/dydrogesterone 2.5 mg] oral Femoston Conti 0.5mg Estradiol&amp;Dydrogesterone vs Oestradiol&amp;Norethisterone acetate</description>
    <arm_group_label>Femoston Conti 0.5mg/2.5mg</arm_group_label>
    <other_name>Femoston Conti 0.5mg/2.5mg film-coated tablets versus</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EVOREL® CONTI</intervention_name>
    <description>Trans-dermal Estradiol 25mcg/norethisterone acetate 85 mcg 1/2 an Evorel Conti patch</description>
    <arm_group_label>EVOREL® CONTI transdermal patches</arm_group_label>
    <other_name>Evorel Conti transdermal patch 25 mcg transdermal dose</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy and postmenopausal woman who have had a normal ultrasound result&#xD;
&#xD;
          -  Aged 40 - 60 years&#xD;
&#xD;
          -  At least 1 year post last menstrual period (per participant report)&#xD;
&#xD;
          -  BMI 18 - 32&#xD;
&#xD;
          -  Normal mammogram within 2 years of study commencement&#xD;
&#xD;
          -  Continue on any concomitant medications without any change during the study give&#xD;
             informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Estrogen or androgen therapy during preceding 3 months&#xD;
&#xD;
          -  Use of hormone implants during the preceding 12 months&#xD;
&#xD;
          -  Have received any medications which may interfere with the study (SSRI, antiandrogens,&#xD;
&#xD;
          -  PDE5 inhibitors, DHEA, SERMS)&#xD;
&#xD;
          -  Have a significant psychiatric disorder&#xD;
&#xD;
          -  Have a history of breast or oestrogen dependent cancer&#xD;
&#xD;
          -  Have diabetes, thrombo-embolic disorders (recent MI angina DVT varicose veins or&#xD;
             recurrent DVT), cardiovascular disease, liver disease any condition affecting&#xD;
             carbohydrate metabolism, uncontrolled hypertension and uncontrolled hyperlipidaemia&#xD;
&#xD;
          -  Untreated endometrial hyperplasia&#xD;
&#xD;
          -  Dubin-Johnson syndrome and Rotor syndrome&#xD;
&#xD;
          -  Undiagnosed vaginal bleeding&#xD;
&#xD;
          -  Women who have had a hysterectomy&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John Stevenson, MBBS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Royal Brompton &amp; Harefield NHS Foundation Trust</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>John Stevenson, MBBS</last_name>
    <phone>0207 351 8112</phone>
    <email>j.stevenson@imperial.ac.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Marie Gerval, MBBS</last_name>
    <phone>07734386042</phone>
    <email>m.gerval@imperial.ac.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Chelsea and Westminster NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <zip>SW10 9NH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nick Panay, MBBS, MRCOG</last_name>
      <phone>0203 331 8112</phone>
      <email>n.panay@imperial.ac.uk</email>
    </contact>
    <investigator>
      <last_name>Nick Panay, MBBS,MRCOG</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Royal Brompton and Harefield NHS Trust</name>
      <address>
        <city>London</city>
        <zip>SW3 6NP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>John Stevenson, MBBS</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Imperial College Healthcare NHS Trust</name>
      <address>
        <city>London</city>
        <zip>W12 0HS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nick Panay, MBBS, MRCOG</last_name>
      <phone>0203 331 8112</phone>
      <email>n.panay@imperial.ac.uk</email>
    </contact>
    <investigator>
      <last_name>Nick Panay, MBBS, MRCOG</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>October 2014</verification_date>
  <study_first_submitted>December 20, 2013</study_first_submitted>
  <study_first_submitted_qc>October 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2014</study_first_posted>
  <last_update_submitted>October 14, 2014</last_update_submitted>
  <last_update_submitted_qc>October 14, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 15, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thrombosis</mesh_term>
    <mesh_term>Venous Thrombosis</mesh_term>
    <mesh_term>Insulin Resistance</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Estradiol 17 beta-cypionate</mesh_term>
    <mesh_term>Estradiol 3-benzoate</mesh_term>
    <mesh_term>Estradiol</mesh_term>
    <mesh_term>Polyestradiol phosphate</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/NCT02264743
org study id: 2013MM002B
secondary id: 2013-002094-22
nct id: NCT02264743
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
Ultra-low-dose oral E2/D will have more beneficial effects than trans-dermal HRT on lipids
      and insulin resistance in postmenopausal women, whilst adverse effects on coagulation will be
      avoided.
Following screening for eligibility, women will be studied at baseline and then randomized to
      one of two groups:

      Group A administered Femoston Conti - oral oestradiol 17β 0.5 mg/dydrogesterone 2.5 mg daily
      for the duration of the treatment phase (24 weeks)

      Group B administered ½ Evorel Conti patches - trans-dermal Estradiol 25 mcg/norethisterone
      acetate 85 mcg (½ Evorel Conti patches) daily for the duration of the treatment phase (24
      weeks).

      Studies will be repeated after 6 months of therapy at the follow up visit.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Thrombin Generation IU/DL
time frame: Six months
measure: triglycerides
time frame: 6 months
description: mmol/L
measure: HDL
time frame: 6 months
description: mmol/L
measure: Total cholesterol
time frame: 6 months
description: mmol/L
measure: LDL
time frame: 6 months
description: mmol/L
measure: D-Dimers
time frame: 6 months
description: ng/ml
measure: APC resistance
time frame: 6 months
description: >2 or <2
measure: fibrinogen
time frame: 6 months
description: g/L
measure: Factor V11
time frame: 6 months
description: U/ml
measure: PAI-1 protein
time frame: 6 months
description: nq/ml
measure: fasting insulin
time frame: 6 months
description: pmol/L
measure: fasting glucose
time frame: 6 months
description: mmol/L
arm group label: Femoston Conti 0.5mg/2.5mg
arm group type: Experimental
description: Ultra low dose, film-coated 17β-estradiol (as hemihydrate) 0.5mg & dydrogesterone 2.5 mg
Once a day
The duration is six months.
Drug intervention: Estradiol&DydrogesteronevsOestradiol&Norethisterone acetate
arm group label: EVOREL® CONTI transdermal patches
arm group type: Active Comparator
description: EVOREL CONTI is a transdermal self adhesive patch which is 0.1 mm in thickness and each patch releases 50mcg of oestradiol and 170mcg of norethisterone acetate over 24 hours .
The Evorel Conti patch is cut in half and applied to the lower part of the body for 3.5 days (delivering approx 25mcg of oestradiol over 24 hours ) this is replaced every 3.5 days .
The duration is six months.
Drug intervention: Estradiol&DydrogesteronevsOestradiol&Norethisterone acetate
intervention type: Drug
intervention name: Femoston Conti
description: Ultra-low-dose oral E2/D [Oestradiol 17β 0.5mg/dydrogesterone 2.5 mg] oral Femoston Conti 0.5mg Estradiol&Dydrogesterone vs Oestradiol&Norethisterone acetate
arm group label: Femoston Conti 0.5mg/2.5mg
other name: Femoston Conti 0.5mg/2.5mg film-coated tablets versus
intervention type: Drug
intervention name: EVOREL® CONTI
description: Trans-dermal Estradiol 25mcg/norethisterone acetate 85 mcg 1/2 an Evorel Conti patch
arm group label: EVOREL® CONTI transdermal patches
other name: Evorel Conti transdermal patch 25 mcg transdermal dose
criteria: 
gender: Female
minimum age: 40 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: John Stevenson, MBBS
role: Principal Investigator
affiliation: Royal Brompton & Harefield NHS Foundation Trust
last name: John Stevenson, MBBS
phone: 0207 351 8112
email: j.stevenson@imperial.ac.uk
last name: Marie Gerval, MBBS
phone: 07734386042
email: m.gerval@imperial.ac.uk
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Thrombosis
mesh term: Venous Thrombosis
mesh term: Insulin Resistance
mesh term: Estradiol 17 beta-cypionate
mesh term: Estradiol 3-benzoate
mesh term: Estradiol
mesh term: Polyestradiol phosphate