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

Sponsor

KK Women's and Children's Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05492487

Collaborator

(none)

Enrollment

Locations

Arms

38.9

Anticipated Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Endometrial Hyperplasia Fertility Issues Disease Regression Treatment Side Effects	Drug: Mirena Drug: Megace	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Participants will be randomised into either the megace group or the Mirena group. There will be sealed envelopes containing a paper with either Mirena or megace printed on each of them. Participants can chose an envelope at random. The patient and PI will not be blinded of the selection in the study.Participants will be randomised into either the megace group or the Mirena group. There will be sealed envelopes containing a paper with either Mirena or megace printed on each of them. Participants can chose an envelope at random. The patient and PI will not be blinded of the selection in the study.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 3, 2020

Anticipated Primary Completion Date :

Mar 31, 2023

Anticipated Study Completion Date :

Mar 31, 2023

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Rate of Regression [Review in 3 months, maximum up to 9 months of treatment.]
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.
Time taken for regression of the disease [Review in 3 months, maximum up to 9 months of treatment.]
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.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 40 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	National University Hospital	Singapore	Singapore	119074
2	Singapore General Hospital	Singapore	Singapore	169608
3	KK Women's and Children's Hospital	Singapore	Singapore	229899