Atypical Endometrial HyperplasiaPhase 2/3NCT04385667
LVN- IUS Versus Oral Megesterol Acetate in Treatment of Atypical Endometrial Hyperplasia
A Phase 2/3 study testing levonorgestrel intrauterine system (LNG-IUD) and Oral Megesterol 160 mg daily in people with Atypical Endometrial Hyperplasia, run by Zagazig University at 1 site in Egypt.
Trial summary
This randomized controlled trial is aimed to compare the efficacy between Megestrol acetate (MA) and the levonorgestrel intrauterine system (LNG-IUD) regarding the ability and duration to produce complete regression for cases with atypical endometrial hyperplasia. Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Atypical Endometrial Hyperplasia
- What is being tested?
- levonorgestrel intrauterine system (LNG-IUD) and Oral Megesterol 160 mg daily
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 143 participants
- Where
- 1 siteEgypt
- Study dates
- 20 May 2020to 25 Dec 2022
- Phase
- Phase 2/3
- 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 Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- All cases with evidence of atypical endometrial hyperplasia declining doing hysterectomy
Who cannot join
- Cases with evidence of associated endometrial cancer.
- Cases with simple hyperplasia without atypia.
- Patients failed to collect at least 2 endometrial samples during treatment course.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Efficacy of Levonorgestrel Intrauterine System Versus Oral Megesterol Acetate in Treatment of Atypical Endometrial Hyperplasia. A Randomized Controlled Trial.
This randomized controlled trial is aimed to compare the efficacy between Megestrol acetate (MA) and the levonorgestrel intrauterine system (LNG-IUD) regarding the ability and duration to produce complete regression for cases with atypical endometrial hyperplasia.
Read the detailed description
Up to 25% of cases with endometrial cancer and atypical hyperplasia occur in premenopausal women. The progressively increasing trend of delay in first conception increases such patients who wish to have children.3 The recommended treatment for EH without atypia is primarily hormonal, whereas the preferred treatment for EH with atypia is hysterectomy given the significant risk for both concurrent and subsequent development of endometrial carcinoma. A dilemma results when EH with atypia is diagnosed in women who wish to retain fertility or declining doing hysterectomy due to concomitant medical morbidities. In these women, a trial of hormone therapy can be considered.4,5 In recent years, progestin therapy has been successfully used to treat selected women with endometrial cancer and atypical hyperplasia who desire to preserve fertility or having severe medical co-morbidities precluding (immediate) surgery. The most common progestin regimens include Megestrol acetate (MA) and the levonorgestrel intrauterine system (LNG-IUD).5-7
- Conditions
- Atypical Endometrial Hyperplasia
- Being tested
- levonorgestrel intrauterine system (LNG-IUD), Oral Megesterol 160 mg daily
- Keywords
- atypical endometrial hyperplasia, levonorgestrel intrauterine system, Megestrol acetate, partial regression
- Medical subject headings
- Endometrial Hyperplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
levonorgestrel intrauterine system (LNG-IUD)Device
Also called • Follow up endometrial sampling will be scheduled for all study patients in 3 months manner for at least one year. Specimens will be reviewed by single expert pathologist.
progestin delivery for regression of atypical endometrial hyperplasia
Oral Megesterol 160 mg dailyDrug
Also called • Follow up endometrial sampling will be scheduled for all study patients in 3 months manner for at least one year. Specimens will be reviewed by single expert pathologist.
progestin delivery for regression of atypical endometrial hyperplasia
| Study group | Role | What they receive |
|---|---|---|
| levonorgestrel intrauterine system (LNG-IUD) | Active comparator | levonorgestrel intrauterine system (LNG-IUD) applied.
* Follow up endometrial sampling will be scheduled for all study patients in 3 months manner for at least one year. Specimens will be reviewed by single expert pathologist.
* Patients with persistent atypical hyperplasia in specimens done after 6 months of start of therapy will be considered resistant to therapy and hysterectomy will be done.
* Primary and secondary outcome data will be collected in tables with the other demographic data. All will be processed in tables for statistical analysis. Receives: Device: levonorgestrel intrauterine system (LNG-IUD) |
| Megestrol acetate (MA) | Active comparator | Megesterol arm will receive 160 mg daily
* Follow up endometrial sampling will be scheduled for all study patients in 3 months manner for at least one year. Specimens will be reviewed by single expert pathologist.
* Patients with persistent atypical hyperplasia in specimens done after 6 months of start of therapy will be considered resistant to therapy and hysterectomy will be done.
* Primary and secondary outcome data will be collected in tables with the other demographic data. All will be processed in tables for statistical analysis. Receives: Drug: Oral Megesterol 160 mg daily |
What is being measured
The primary outcome is the main question the study is designed to answer.
The success rate to accomplish complete regression of atypical endometrial hyperplasia
The success rate to accomplish complete regression of atypical endometrial hyperplasia
Measured: 15 month
Secondary outcomes (5)
a- Duration needed to accomplish the complete recovery
time till regression
Measured: 15 months
b- The partial regression and failure rates.
incidence of partial regression and therapy failure
Measured: 8 months
c- Differential response rates between premenopausal and postmenopausal cases.
response rate in both premenopause and postmenopause women
Measured: 15 months
d- The risk of thromboembolic complications
incidence of thromboembolism with therapy
Measured: 15 months
f- Metabolic complications rates
occurence of diabetes or hypertension ...ets
Measured: 15 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2020
- Study start20 May 2020
- Primary completion1 Dec 2022
- Study completion25 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Atypical Endometrial HyperplasiaStudies of the same condition, open and under way.
- More trials run by Zagazig UniversityThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 143 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zagazig University
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Hytham Atia, Zagazig University
- Investigators
- Amr Alnemr, M.D., Principal investigator, Faculty of Medicine- Zagazig universityHytham Atia, M.D., Principal investigator, Faculty of Medicine- Zagazig university
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04385667
- Sponsor's protocol ID
- LVN-IUS vs Megace for AEH
- Status last verified
- Dec 2022
- First submitted
- 9 May 2020
- Last updated
- 3 Jan 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Armstrong AJ, Hurd WW, Elguero S, Barker NM, Zanotti KM. Diagnosis and management of endometrial hyperplasia. J Minim Invasive Gynecol. 2012 Sep-Oct;19(5):562-71. doi: 10.1016/j.jmig.2012.05.009. Epub 2012 Aug 3.
PubMed 22863972Salman MC, Usubutun A, Boynukalin K, Yuce K. Comparison of WHO and endometrial intraepithelial neoplasia classifications in predicting the presence of coexistent malignancy in endometrial hyperplasia. J Gynecol Oncol. 2010 Jun;21(2):97-101. doi: 10.3802/jgo.2010.21.2.97. Epub 2010 Jun 30.
PubMed 20613899Zhou R, Yang Y, Lu Q, Wang J, Miao Y, Wang S, Wang Z, Zhao C, Wei L. Prognostic factors of oncological and reproductive outcomes in fertility-sparing treatment of complex atypical hyperplasia and low-grade endometrial cancer using oral progestin in Chinese patients. Gynecol Oncol. 2015 Dec;139(3):424-8. doi: 10.1016/j.ygyno.2015.09.078. Epub 2015 Sep 30.
PubMed 26428941Gallos ID, Shehmar M, Thangaratinam S, Papapostolou TK, Coomarasamy A, Gupta JK. Oral progestogens vs levonorgestrel-releasing intrauterine system for endometrial hyperplasia: a systematic review and metaanalysis. Am J Obstet Gynecol. 2010 Dec;203(6):547.e1-10. doi: 10.1016/j.ajog.2010.07.037.
PubMed 20934679Alnemr AA, Harb OA, Atia H. The efficacy of the levonorgestrel intrauterine system versus oral megestrol acetate in treating atypical endometrial hyperplasia: a superior randomized controlled trial. J Gynecol Oncol. 2024 Sep;35(5):e62. doi: 10.3802/jgo.2024.35.e62. Epub 2024 Feb 22.
PubMed 38425141
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Efficacy of Levonorgestrel Intrauterine System Versus Oral Megesterol Acetate in Treatment of Atypical Endometrial Hyperplasia. A Randomized Controlled Trial.
- ClinicalTrials.gov ID
- NCT04385667
- Acronym / sponsor ID
- LVN-IUS vs Megace for AEH
- Conditions
- Atypical Endometrial Hyperplasia
- Keywords
- atypical endometrial hyperplasia, levonorgestrel intrauterine system, Megestrol acetate, partial regression
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 143 participants (actual)
- Lead sponsor
- Zagazig UniversityOther government
- Study start
- 20 May 2020 (actual)
- Primary completion
- 1 Dec 2022 (actual)
- Study completion
- 25 Dec 2022 (actual)
- First posted
- 13 May 2020 (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.
This randomized controlled trial is aimed to compare the efficacy between Megestrol acetate (MA) and the levonorgestrel intrauterine system (LNG-IUD) regarding the ability and duration to produce complete regression for cases with atypical endometrial hyperplasia.
Detailed description
Up to 25% of cases with endometrial cancer and atypical hyperplasia occur in premenopausal women. The progressively increasing trend of delay in first conception increases such patients who wish to have children.3 The recommended treatment for EH without atypia is primarily hormonal, whereas the preferred treatment for EH with atypia is hysterectomy given the significant risk for both concurrent and subsequent development of endometrial carcinoma. A dilemma results when EH with atypia is diagnosed in women who wish to retain fertility or declining doing hysterectomy due to concomitant medical morbidities. In these women, a trial of hormone therapy can be considered.4,5 In recent years, progestin therapy has been successfully used to treat selected women with endometrial cancer and atypical hyperplasia who desire to preserve fertility or having severe medical co-morbidities precluding (immediate) surgery. The most common progestin regimens include Megestrol acetate (MA) and the levonorgestrel intrauterine system (LNG-IUD).5-7
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| levonorgestrel intrauterine system (LNG-IUD) | Active comparator | Device: levonorgestrel intrauterine system (LNG-IUD)levonorgestrel intrauterine system (LNG-IUD) applied. * Follow up endometrial sampling will be scheduled for all study patients in 3 months manner for at least one year. Specimens will be reviewed by single expert pathologist. * Patients with persistent atypical hyperplasia in specimens done after 6 months of start of therapy will be considered resistant to therapy and hysterectomy will be done. * Primary and secondary outcome data will be collected in tables with the other demographic data. All will be processed in tables for statistical analysis. |
| Megestrol acetate (MA) | Active comparator | Drug: Oral Megesterol 160 mg dailyMegesterol arm will receive 160 mg daily * Follow up endometrial sampling will be scheduled for all study patients in 3 months manner for at least one year. Specimens will be reviewed by single expert pathologist. * Patients with persistent atypical hyperplasia in specimens done after 6 months of start of therapy will be considered resistant to therapy and hysterectomy will be done. * Primary and secondary outcome data will be collected in tables with the other demographic data. All will be processed in tables for statistical analysis. |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- All cases with evidence of atypical endometrial hyperplasia declining doing hysterectomy
Key exclusion criteria (3 listed)
- Cases with evidence of associated endometrial cancer.
- Cases with simple hyperplasia without atypia.
- Patients failed to collect at least 2 endometrial samples during treatment course.
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 |
|---|---|---|
| levonorgestrel intrauterine system (LNG-IUD)Also: • Follow up endometrial sampling will be scheduled for all study patients in 3 months manner for at least one year. Specimens will be reviewed by single expert pathologist.progestin delivery for regression of atypical endometrial hyperplasia | Device | levonorgestrel intrauterine system (LNG-IUD) |
| Oral Megesterol 160 mg dailyAlso: • Follow up endometrial sampling will be scheduled for all study patients in 3 months manner for at least one year. Specimens will be reviewed by single expert pathologist.progestin delivery for regression of atypical endometrial hyperplasia | Drug | Megestrol acetate (MA) |
Primary outcome
The success rate to accomplish complete regression of atypical endometrial hyperplasia
Time frame: 15 month
The success rate to accomplish complete regression of atypical endometrial hyperplasia
5 secondary outcomes
a- Duration needed to accomplish the complete recovery
Time frame: 15 months
b- The partial regression and failure rates.
Time frame: 8 months
c- Differential response rates between premenopausal and postmenopausal cases.
Time frame: 15 months
d- The risk of thromboembolic complications
Time frame: 15 months
f- Metabolic complications rates
Time frame: 15 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2023.
- Background: PubMed 22863972Armstrong AJ, Hurd WW, Elguero S, Barker NM, Zanotti KM. Diagnosis and management of endometrial hyperplasia. J Minim Invasive Gynecol. 2012 Sep-Oct;19(5):562-71. doi: 10.1016/j.jmig.2012.05.009. Epub 2012 Aug 3.
- Background: PubMed 20613899Salman MC, Usubutun A, Boynukalin K, Yuce K. Comparison of WHO and endometrial intraepithelial neoplasia classifications in predicting the presence of coexistent malignancy in endometrial hyperplasia. J Gynecol Oncol. 2010 Jun;21(2):97-101. doi: 10.3802/jgo.2010.21.2.97. Epub 2010 Jun 30.
- Background: PubMed 26428941Zhou R, Yang Y, Lu Q, Wang J, Miao Y, Wang S, Wang Z, Zhao C, Wei L. Prognostic factors of oncological and reproductive outcomes in fertility-sparing treatment of complex atypical hyperplasia and low-grade endometrial cancer using oral progestin in Chinese patients. Gynecol Oncol. 2015 Dec;139(3):424-8. doi: 10.1016/j.ygyno.2015.09.078. Epub 2015 Sep 30.
- Background: PubMed 20934679Gallos ID, Shehmar M, Thangaratinam S, Papapostolou TK, Coomarasamy A, Gupta JK. Oral progestogens vs levonorgestrel-releasing intrauterine system for endometrial hyperplasia: a systematic review and metaanalysis. Am J Obstet Gynecol. 2010 Dec;203(6):547.e1-10. doi: 10.1016/j.ajog.2010.07.037.
- Derived from this study: PubMed 38425141Alnemr AA, Harb OA, Atia H. The efficacy of the levonorgestrel intrauterine system versus oral megestrol acetate in treating atypical endometrial hyperplasia: a superior randomized controlled trial. J Gynecol Oncol. 2024 Sep;35(5):e62. doi: 10.3802/jgo.2024.35.e62. Epub 2024 Feb 22.
- 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.
Amr Alnemr, M.D. principal investigator
Faculty of Medicine- Zagazig university
Hytham Atia, M.D. principal investigator
Faculty of Medicine- Zagazig university
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing levonorgestrel intrauterine system (LNG-IUD) and Oral Megesterol 160 mg daily in people with Atypical Endometrial Hyperplasia, run by Zagazig University at 1 site in Egypt.
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 1 inclusion and 3 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: finished, as of the sponsor's last update on 3 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The success rate to accomplish complete regression of atypical endometrial hyperplasia (time frame: 15 month). 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 NCT04385667, which also lists 5 linked publications.
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 3 Jan 2023.