A Pilot Study on Fertility Conservative Treatment of Atypical Endometrial Hyperplasia in Singapore

The investigators' objective is to determine the regression rate, side effects and acceptability of Mirena compared to megace in the treatment of atypical endometrial hyperplasia among women desiring fertility.

Study Overview

• Status: Recruiting
• Conditions: Endometrial Hyperplasia; Fertility Issues; Treatment Side Effects; Disease Regression
• Intervention / Treatment: Drug: Mirena; Drug: Megace

Detailed Description

Atypical endometrial hyperplasia is a growing clinical problem that increases the risk of carcinogenesis and negatively impacts fertility. Although oral medical treatment may lead to regression in up to 90% of patients, they are associated with adverse side effects such as weight gain, that negatively affects fertility. To-date, there has been no RCTs evaluating the performance of the Mirena Intrauterine System (IUS) with megestrol acetate (megace) (the most effective and commonly used progestogen) in treating women with atypical hyperplasia who still desire fertility.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jessie Phoon, Dr; Phone Number: 98242158; Email: jessie.phoon.w.l@singhealth.com.sg

Study Locations

• Singapore
  • Singapore, Singapore, 229899
    • Recruiting
    • KK Women's and Children's Hospital
    • Contact: Doris Ong; Phone Number: 98242158; Email: ong.mah.lay@kkh.com.sg
    • Principal Investigator: Jessie Phoon, Dr
  • Singapore, Singapore, 169608
    • Recruiting
    • Singapore General Hospital
    • Contact: Doris Ong; Phone Number: 98242158; Email: ong.mah.lay@kkh.com.sg
    • Principal Investigator: Nadarajah Ravichandran, Dr
  • Singapore, Singapore, 119074
    • Recruiting
    • National University Hospital
    • Contact: Doris Ong; Phone Number: 98242158; Email: ong.mah.lay@kkh.com.sg
    • Principal Investigator: Pearl Tong, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• All women diagnosed with atypical hyperplasia aged 21 years to 40 years
• Keen for fertility-preserving treatment

Exclusion Criteria:

• Patients who are currently undergoing treatment for atypical hyperplasia
• Patients with a history of endometrial carcinoma

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: Mirena Arm; The patients in the Mirena arm will have a Mirena inserted at time of recruitment of the study. An endometrial biopsy will be performed to assess for disease progression, regression or persistence after 3 months. The endometrial biopsy will be performed via bedside endometrial sampling or hysteroscopic biopsy. As Mirena can be used for treatment of atypical hyperplasia as well as endometrial protection (decreases the risk of endometrial hyperplasia recurrence), the option of keeping or changing the Mirena during biopsy will be discussed with the patient.	Drug: Mirena; Mirena Intrauterine System (Mirena-IUS) is a levonorgestrel-releasing intrauterine system. Mirena consists of a T-shaped polyethylene frame (T-body) with a steroid reservoir (hormone elastomer core) around the vertical stem. The reservoir consists of a white or almost white cylinder, made of a mixture of levonorgestrel and silicone (polydimethylsiloxane), containing a total of 52 mg levonorgestrel. Mirena is approved for intrauterine contraception and in 2009 to treat heavy periods for women who choose intrauterine contraception. Mirena is often used off-label for the treatment of endometrial hyperplasia. Levonorgestrel is a progestogen used in a variety of contraceptive products. Low doses of levonorgestrel can be administered into the uterine cavity with the Mirena intrauterine delivery system. Mirena has mainly local progestogenic effects in the uterine cavity.
Experimental: Megace Arm; The patients in the megace arm will have be prescribed 3 months of oral megace at time of recruitment of the study. An endometrial biopsy will be performed to assess for disease progression, regression or persistence after 3 months. The endometrial biopsy will be performed via bedside endometrial sampling or hysteroscopic biopsy.	Drug: Megace; Megestrol acetate (Megace) is a synthetic derivative of the natural occurring steroid hormone, progesterone. It is licensed for the treatment of anorexia, cachexia or unexplained weight loss in patients with a diagnosis of acquired immunodeficiency syndrome (AIDS) and palliative treatment of advanced breast or endometrial cancer. Megace is often used off-label for the treatment of endometrial hyperplasia. While the precise mechanism by which Megace produces its antineoplastic effects against endometrial carcinoma and endometrial hyperplasia is unknown at the present time, inhibition of pituitary gonadotrophin production and resultant decrease in estrogen secretion may be factors. There is evidence to suggest a local effect as a result of the marked changes brought about by the direct instillation of progestational agents into the endometrial cavity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Regression	Participants will be reviewed in clinic every 3 months. An endometrial biopsy via hysteroscopy or bedside endometrial sampling will be performed to assess persistence, progression or resolution of the disease.	Review in 3 months, maximum up to 9 months of treatment.
Time taken for regression of the disease	Participants will be reviewed in clinic every 3 months. An endometrial biopsy via hysteroscopy or bedside endometrial sampling will be performed to assess persistence, progression or resolution of the disease.	Review in 3 months, maximum up to 9 months of treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Acceptability	Number of participants who are keen to continue their current treatment or change the treatment, at the end of 3rd months follow-up.	Review in 3rd months.
Patient Acceptability	Number of participants who are keen to continue their current treatment or change the treatment, at the end of 6th months follow-up.	Review in 6th months.
Patient Acceptability	Number of participants who are keen to continue their current treatment or change the treatment, at the end of 9th months follow-up.	Review in 9th months.
Side Effects	Number of participants with side effects such as irregular bleeding, nausea/bloatedness or acne.	Through study completion, an average of 9 months.

Collaborators and Investigators

• Sponsor: KK Women's and Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2020
• Primary Completion (Anticipated): March 31, 2023
• Study Completion (Anticipated): March 31, 2023

Study Registration Dates

• First Submitted: April 7, 2022
• First Submitted That Met QC Criteria: August 5, 2022
• First Posted (Actual): August 8, 2022

Study Record Updates

• Last Update Posted (Actual): August 8, 2022
• Last Update Submitted That Met QC Criteria: August 5, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Fertility; Endometrial Hyperplasia; Disease Regression; Randomised Clinical Trial; Mirena IUS; Megace
• Additional Relevant MeSH Terms: Pathologic Processes; Uterine Diseases; Infertility; Hyperplasia; Endometrial Hyperplasia; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Central Nervous System Stimulants; Appetite Stimulants; Levonorgestrel; Megestrol Acetate
• Other Study ID Numbers: CIRB 2019/2551

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No