Oral Verses Patch Trial In Menopausal Women - Individualisation of Oestrogen Therapy (OPTIMISE)

Comparison of Ultra-low-dose Oral Versus Trans-dermal Hormone Therapy on Coagulation Activation and Metabolic Risk Factors for Cardiovascular Disease

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.

Study Overview

• Status: Unknown
• Conditions: Venous Thrombosis; Insulin Resistance
• Intervention / Treatment: Drug: Femoston Conti; Drug: EVOREL® CONTI

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W12 0HS
    • Recruiting
    • Imperial College Healthcare NHS Trust
    • Contact: Nick Panay, MBBS, MRCOG; Phone Number: 0203 331 8112; Email: n.panay@imperial.ac.uk
    • Sub-Investigator: Nick Panay, MBBS, MRCOG
  • London, United Kingdom, SW10 9NH
    • Recruiting
    • Chelsea and Westminster NHS Foundation Trust
    • Contact: Nick Panay, MBBS, MRCOG; Phone Number: 0203 331 8112; Email: n.panay@imperial.ac.uk
    • Sub-Investigator: Nick Panay, MBBS,MRCOG
  • London, United Kingdom, SW3 6NP
    • Recruiting
    • Royal Brompton and Harefield NHS Trust
    • Principal Investigator: John Stevenson, MBBS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 56 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Healthy and postmenopausal woman who have had a normal ultrasound result
• Aged 40 - 60 years
• At least 1 year post last menstrual period (per participant report)
• BMI 18 - 32
• Normal mammogram within 2 years of study commencement
• Continue on any concomitant medications without any change during the study give informed consent

Exclusion Criteria:

• Estrogen or androgen therapy during preceding 3 months
• Use of hormone implants during the preceding 12 months
• Have received any medications which may interfere with the study (SSRI, antiandrogens,
• PDE5 inhibitors, DHEA, SERMS)
• Have a significant psychiatric disorder
• Have a history of breast or oestrogen dependent cancer
• Have diabetes, thrombo-embolic disorders (recent MI angina DVT varicose veins or recurrent DVT), cardiovascular disease, liver disease any condition affecting carbohydrate metabolism, uncontrolled hypertension and uncontrolled hyperlipidaemia
• Untreated endometrial hyperplasia
• Dubin-Johnson syndrome and Rotor syndrome
• Undiagnosed vaginal bleeding
• Women who have had a hysterectomy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Femoston Conti 0.5mg/2.5mg; 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	Drug: Femoston Conti; 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; Other Names: Femoston Conti 0.5mg/2.5mg film-coated tablets versus
Active Comparator: EVOREL® CONTI transdermal patches; 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	Drug: EVOREL® CONTI; Trans-dermal Estradiol 25mcg/norethisterone acetate 85 mcg 1/2 an Evorel Conti patch; Other Names: Evorel Conti transdermal patch 25 mcg transdermal dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Thrombin Generation IU/DL	Six months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
triglycerides	mmol/L	6 months
HDL	mmol/L	6 months
Total cholesterol	mmol/L	6 months
LDL	mmol/L	6 months
D-Dimers	ng/ml	6 months
APC resistance	>2 or <2	6 months
fibrinogen	g/L	6 months
Factor V11	U/ml	6 months
PAI-1 protein	nq/ml	6 months
fasting insulin	pmol/L	6 months
fasting glucose	mmol/L	6 months

Collaborators and Investigators

• Sponsor: Royal Brompton & Harefield NHS Foundation Trust
• Collaborators: Chelsea and Westminster NHS Foundation Trust; Imperial College Healthcare NHS Trust
• Investigators: Principal Investigator: John Stevenson, MBBS, Royal Brompton & Harefield NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Anticipated): November 1, 2014
• Study Completion (Anticipated): November 1, 2015

Study Registration Dates

• First Submitted: December 20, 2013
• First Submitted That Met QC Criteria: October 14, 2014
• First Posted (Estimate): October 15, 2014

Study Record Updates

• Last Update Posted (Estimate): October 15, 2014
• Last Update Submitted That Met QC Criteria: October 14, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Embolism and Thrombosis; Hyperinsulinism; Insulin Resistance; Thrombosis; Venous Thrombosis; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Estradiol; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate
• Other Study ID Numbers: 2013MM002B; 2013-002094-22 (EudraCT Number)