Clinical trial NCT03241888: Megestrol Acetate Plus LNG-IUS in Young Women With Endometrial Atypical Hyperplasia
Official title: Megestrol Acetate Plus LNG-IUS to Megestrol Acetate or LNG-IUS in Young Women With Endometrial Atypical Hyperplasia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Atypical Endometrial Hyperplasia
Keywords: Levonorgestrel-releasing intrauterine system
megestrol acetate
Atypical Endometrial Hyperplasia
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2017-08-08
Enrollment: 180
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To see if megestrol acetate plus Levonorgestrel-releasing intrauterine system (LNG-IUS) will not be inferior to returning the endometrial tissue to a normal state than megestrol acetate or LNG-IUS alone in patients with endometrial atypical hyperplasia.

Detailed description: After diagnosed of endometrial atypical hyperplasia (EAH) by hysteroscopy, patients will be enrolled. Age, waist circumstances, blood pressure, basic history of infertility, blood pressure, serum lipid level and side effects will be collected. Blood tests, including fasting blood glucose (FBG), postprandial blood glucose (PBG), fasting insulin (FINS), SHBG, sex hormone levels, blood lipids and anti-müllerian hormone(AMH) will be performed before treatment to evacuate their metabolic conditions.

Patients are randomized to 1 of 3 treatment groups. Patients will receive MA (megestrol acetate) 160 mg by mouth daily for at least 3 months on Arm I. Patients will receive LNG-IUS insertion on Arm II and MA 160 mg plus LNG-IUS insertion on Arm III. Then an hysteroscope will be used to evaluate the endometrial condition every 3 months, and the findings will be recorded. For patients with EAH, complete response (CR) is defined as the reversion of endometrial atypical hyperplasia to proliferative or secretory endometrium; partial response (PR) is defined as regression to simple or complex hyperplasia without atypia; no response (NR) is defined as the persistence of the disease; and progressive disease (PD) is defined as the appearance of endometrial cancer in patients. Continuous therapies will be needed in PR, NR or PD.

After completion of study treatment, 2 months of maintenance treatment will be recommended for patients with CR, and participants will be followed up for 2 years.

Eligibility criteria: Inclusion Criteria:

* Primarily have a confirmed diagnosis of endometrial atypical hyperplasia based upon hysteroscopy
* Have a desire for remaining reproductive function or uterus
* Need to be able to undergo correlative treatment and follow-up

Exclusion Criteria:

* Acute liver disease or liver tumor (benign or malignant) or renal dysfunction
* Pregnancy or suspicion of pregnancy
* Have a history of EAH and have disease relapse during Merina insertion
* Under treatment of high-dose progestin therapy more than 3 months in recent 6 months
* Congenital or acquired uterine anomaly including fibroids if they distort the uterine cavity
* Confirmed diagnosis of malignant tumor in genital system
* Acute severe disease such as stroke or heart infarction or a history of thrombosis disease
* Hypersensitivity or contradiction to any component of this product
* Ask for removal of the uterus or other conservative treatment
* Smoker(\>15 cigarettes a day)

Primary outcomes:
measure: Pathological response rate
timeFrame: From date of randomization until the date of CR or date of hysterectomy, whichever came first, assessed up to 12 months
measure: Pathological response time
timeFrame: From date of randomization until the date of CR or date of hysterectomy, whichever came first, assessed up to 12 months
Secondary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: up to 2 years after the treatment for each patient
measure: Rate of relapse
timeFrame: up to 2 years after the treatment for each patient
measure: Rate of pregnancy
timeFrame: up to 2 years after the treatment for each patient
measure: Compliance
timeFrame: up to 2 years after the treatment for each patient
Other outcomes:
measure: Economic consequences through study completion
timeFrame: From date of randomization until the date of CR or date of hysterectomy, whichever came first, assessed up to 12 months
Locations:
city: Shanghai
country: China
facility: Obstetrics and Gynecology Hospital, Fudan University
state: Shanghai
Study officials:
References:
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citation: Chen M, Jin Y, Li Y, Bi Y, Shan Y, Pan L. Oncologic and reproductive outcomes after fertility-sparing management with oral progestin for women with complex endometrial hyperplasia and endometrial cancer. Int J Gynaecol Obstet. 2016 Jan;132(1):34-8. doi: 10.1016/j.ijgo.2015.06.046. Epub 2015 Oct 1.
citation: Mittermeier T, Farrant C, Wise MR. Levonorgestrel-releasing intrauterine system for endometrial hyperplasia. Cochrane Database Syst Rev. 2020 Sep 6;9(9):CD012658. doi: 10.1002/14651858.CD012658.pub2.