Clinical trial NCT01074892: A Study Comparing Mirena and Systemic Progestin for Endometrial Hyperplasia
Official title: A Multicenter Study Comparing Mirena and Systemic Progestin for Endometrial Hyperplasia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Endometrial Hyperplasia
Keywords: endometrial hyperplasia treatment MPA per os LNG-IUD
Lead sponsor: University Hospital of North Norway
Sponsor class: OTHER
Collaborators: name: Helse Nord
name: Norwegian Cancer Society
First posted: 2010-02-24
Enrollment: 170
Sex: FEMALE
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Randomized controlled multi-center study with three arms including 200 patients with low risk endometrial hyperplasia. After confirmed diagnosis the patients will receive one of the following treatments:

1. Provera (Medroxyprogesterone (MPA)/progestin) 10 mg per oral treatment for 6 months 10 day each cycle,
2. MPA 10 mg continuously for 6 months,
3. Mirena (Levonorgestrel) impregnated IUD for 6 months.

Detailed description: Background:

Endometrial cancer is the most common gynecologic cancer in the Western world and the incidence is still increasing. Endometrial cancer is principally developing through preliminary stages called endometrial hyperplasia and 10-30 per cent will develop into carcinoma when left untreated. The incidence of endometrial cancer in Norway is presently about 650 cases per year and about 3000 cases of endometrial hyperplasia are estimated. Thus,correct and optimal treatment of endometrial hyperplasia will contribute to prevent endometrial cancer development and also in the long term, to reduce the incidence of endometrial cancer. Correct treatment of endometrial hyperplasia includes operative treatment with hysterectomy of the high risk cases and conservative treatment and follow up for patients with lower risk. As diagnostics of endometrial hyperplasia has been a challenge to pathologists, overtreatment of patients with low risk of cancer development is unfortunately still a problem. In the present study an objective scoring system, D-score, is used to classify the patients into low and high risk hyperplasia. D-score in an objective morphometric analysis and the scoring system has proved reliable to predict the prognosis of each single case as to cancer development or not. By tradition low risk endometrial hyperplasia is treated conservatively with progestin hormones, however, no national routines really exist according to dose, type of progestin, treatment time or distribution route, however, varying doses of per oral treatment is mostly used.

Progestins hormones are known to have a growth regulatory effect on the uterine mucosa. However, treatment success after per oral therapy has shown that up to 50% are non-responders after per oral treatment. On the other hand a few recent studies have reported successful results after using the LNG-IUD as treatment for endometrial hyperplasia with 100 per cent treatment response.

The levonorgestrel impregnated impregnated intrauterine originally constructed for menorrhagia and contraceptive use, is delivering more than hundred times increased concentration of progesterone to the uterine mucosa compared to per oral therapy. Thus , the favourable treatment is attributable to the increased concentration of progestins obtained in the uterine mucosa. Another advantage is that treatment can last for years and that side-effects seen for per oral treatment after progestin therapy can be avoided.

Inclusion:

Most of the patients in the present study are seeing their gynecologist due to irregular bleedings.Biopsy is routinely taken by the gynecologist to exclude malignancy or verify hyperplasia. The biopsy is investigated routinely by a the local pathologist. If the diagnosis of hyperplasia is verified and the patient fulfils the inclusion criteria, the histological specimen is sent to the laboratory in Tromsø for D-score. When D-score is \>0, the patient may be included in the study.

D-score:

The D-score system is dividing the patients into three risk groups:

1. Patients having a D-score \<0 are shown to have a high risk of cancer development are recommended hysterectomy.
2. Patients having D-score \>1 have very low risk of cancer development and are recommended progestin treatment.
3. Patients having D-score 0-1 have an uncertain risk of cancer development and may be treated conservatively. Only patients with D-score \> 0 may be included in the study.

Randomization:

When the gynecologist receive the diagnosis and the D-score results and the D-score is in accordance with the inclusion criteria, the patients is asked by her gynecologist to be included in the study.

If consent is given, the randomization is performed by telephone contact with the randomization office , UNN, Tromsø, after written informed consent. The patient is free to leave the study any time without argument.

Treatment:

After randomization the treatment according to assigned treatment arm can be started. During the therapy period the patient will be controlled with repeat biopsy after 3 months and at the end of treatment after 6 months. D-score is repeated if hyperplasia persists. If a negative D-score is performed, the patient will have to leave the study. If D-score is still positive the patient will also leave the study, new therapy is then decided by the local gynecologist.

Control:

All patients will be controlled with repeat biopsy every six month for two years after end of therapy. If recurrence of hyperplasia occurs the patient will leave the study and receive other therapy decided by her own gynecologist after repeated D-score.

Side effects:

All side effects which can be related to treatment during treatment and/or follow-up will be reported.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed endometrial hyperplasia,
* D-score \> 0,
* Age 30-70 years,
* No contra-indications against progestin hormones,
* Written consent,
* Patients who have been treated with transcervical resection need a histologically confirmed diagnosis of hyperplasia taken after the TCR

Exclusion Criteria:

* D-score \< 0,
* Age \< 30 or \> 70,
* Increased sensitivity to progestins,
* Pregnancy,
* Infection or cancer in genitalia or mammary gland,
* Liver disease,
* Serious thrombophlebitis.

Primary outcomes:
measure: Regression of hyperplasia related to treatment arm after 6 months of therapy
timeFrame: Six months
Secondary outcomes:
measure: Recurrence of hyperplasia related to treatment arm during follow-up period
timeFrame: Two years
measure: Side effects during treatment
timeFrame: Two years
Other outcomes:
Locations:
city: Tromsø
country: Norway
facility: University Hospital of North Norway
state: Troms
Study officials:
affiliation: University of Tromso
name: Anne Ørbo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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