Endometrial HyperplasiaPhase 2NCT05492487
A Pilot Study on Fertility Conservative Treatment of Atypical Endometrial Hyperplasia in Singapore
A Phase 2 study testing Mirena and Megace in people with Endometrial Hyperplasia and Fertility Issues, run by KK Women's and Children's Hospital at 3 sites in Singapore.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 40 years, women only
- Conditions the study is for
- Endometrial Hyperplasia, Fertility Issues, Disease Regression
- What is being tested?
- Mirena and Megace
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 3 sitesSingapore
- Study dates
- 3 Jan 2020to 31 Mar 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- All women diagnosed with atypical hyperplasia aged 21 years to 40 years
- Keen for fertility-preserving treatment
Who cannot join
- Patients who are currently undergoing treatment for atypical hyperplasia
- Patients with a history of endometrial carcinoma
Trial locations and contacts
3 sites in 1 country.
Singapore3 sites, 3 recruiting
- Recruiting
National University Hospital
Singapore, 119074
Doris ong, 98242158, ong.mah.lay@kkh.com.sg
Pearl Tong, Dr
- Recruiting
Singapore General Hospital
Singapore, 169608
Doris Ong, 98242158, ong.mah.lay@kkh.com.sg
Nadarajah Ravichandran, Dr
- Recruiting
KK Women's and Children's Hospital
Singapore, 229899
Doris Ong, 98242158, ong.mah.lay@kkh.com.sg
Jessie Phoon, Dr
About this study
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.
Read the 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.
- Being tested
- Mirena, Megace
- Keywords
- Endometrial Hyperplasia, Fertility, Disease Regression, Randomised Clinical Trial, Mirena IUS, Megace
- Medical subject headings
- Endometrial Hyperplasia, Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MirenaDrug
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.
MegaceDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Mirena Arm | Experimental | 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. Receives: Drug: Mirena |
| Megace Arm | Experimental | 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. Receives: Drug: Megace |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Review in 3 months, maximum up to 9 months of treatment.
Secondary outcomes (4)
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.
Measured: 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.
Measured: 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.
Measured: Review in 9th months.
Side Effects
Number of participants with side effects such as irregular bleeding, nausea/bloatedness or acne.
Measured: Through study completion, an average of 9 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2022
- Study start3 Jan 2020
- Primary completion31 Mar 2023 (estimated)
- Study completion31 Mar 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Endometrial HyperplasiaStudies of the same condition, open and under way.
- More trials run by KK Women's and Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- KK Women's and Children's Hospital
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Phoon Wai Leng Jessie, KK Women's and Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05492487
- Sponsor's protocol ID
- CIRB 2019/2551
- Status last verified
- Aug 2022
- First submitted
- 7 Apr 2022
- Last updated
- 8 Aug 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Goh CSY, Loh MJM, Lim WW, Ang JX, Nadarajah R, Yong TT, Tong P, Yeo YC, Phoon JWL. A multi-centre randomised controlled trial comparing megestrol acetate to levonorgestrel-intrauterine system in fertility sparing treatment of atypical endometrial hyperplasia. J Assist Reprod Genet. 2024 Sep;41(9):2485-2494. doi: 10.1007/s10815-024-03172-z. Epub 2024 Aug 31.
PubMed 39215793
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study on Fertility Conservative Treatment of Atypical Endometrial Hyperplasia in Singapore
- ClinicalTrials.gov ID
- NCT05492487
- Acronym / sponsor ID
- CIRB 2019/2551
- Keywords
- Endometrial Hyperplasia, Fertility, Disease Regression, Randomised Clinical Trial, Mirena IUS, Megace
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- KK Women's and Children's HospitalOther government
- Study start
- 3 Jan 2020 (actual)
- Primary completion
- 31 Mar 2023 (estimated)
- Study completion
- 31 Mar 2023 (estimated)
- First posted
- 8 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Mirena Arm | Experimental | Drug: MirenaThe 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. |
| Megace Arm | Experimental | Drug: MegaceThe 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. |
Who may qualify
- Ages
- 21 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- All women diagnosed with atypical hyperplasia aged 21 years to 40 years
- Keen for fertility-preserving treatment
Key exclusion criteria (2 listed)
- Patients who are currently undergoing treatment for atypical hyperplasia
- Patients with a history of endometrial carcinoma
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MirenaMirena 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. | Drug | Mirena Arm |
| MegaceMegestrol 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. | Drug | Megace Arm |
Primary outcome
Rate of Regression
Time frame: 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
Time frame: 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.
4 secondary outcomes
Patient Acceptability
Time frame: Review in 3rd months.
Patient Acceptability
Time frame: Review in 6th months.
Patient Acceptability
Time frame: Review in 9th months.
Side Effects
Time frame: Through study completion, an average of 9 months.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2022.
- Derived from this study: PubMed 39215793Goh CSY, Loh MJM, Lim WW, Ang JX, Nadarajah R, Yong TT, Tong P, Yeo YC, Phoon JWL. A multi-centre randomised controlled trial comparing megestrol acetate to levonorgestrel-intrauterine system in fertility sparing treatment of atypical endometrial hyperplasia. J Assist Reprod Genet. 2024 Sep;41(9):2485-2494. doi: 10.1007/s10815-024-03172-z. Epub 2024 Aug 31.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mirena and Megace in people with Endometrial Hyperplasia and Fertility Issues, run by KK Women's and Children's Hospital at 3 sites in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jessie Phoon, Dr (98242158, jessie.phoon.w.l@singhealth.com.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Regression (time frame: Review in 3 months, maximum up to 9 months of treatment.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05492487, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Aug 2022.