A Study Comparing Mirena and Systemic Progestin for Endometrial Hyperplasia

NCT01074892 | Completed Phase 4

• 1 other identifier: REK nr 25/2004
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 1

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

Conditions

Endometrial Hyperplasia

Keywords

endometrial hyperplasia treatment MPA per os LNG-IUD

Outcome Measures

Primary Outcomes (1)

• Regression of hyperplasia related to treatment arm after 6 months of therapy

  Six months

Secondary Outcomes (2)

• Recurrence of hyperplasia related to treatment arm during follow-up period

  Two years

• Side effects during treatment

  Two years

Study Arms (3)

MPA 10 mg per oral cyclic for 6 months

ACTIVE COMPARATOR

The peroral treatment is used 10 days each month

Drug: Provera (medroxyprogesterone/progestin)

MPA 10 mg per os continuous 6 months

ACTIVE COMPARATOR

Per oral MPA 10 mg is taken daily for 6 months

Drug: Provera (medroxyprogesterone)

LNG-IUD for 6 months

ACTIVE COMPARATOR

Levonorgestrel impregnated IUD is inserted into the uterine cavity and kept in situ for 6 months

Device: Mirena (levonorgestrel)

Interventions

Provera (medroxyprogesterone/progestin) DRUG

10 mg tablet, 1 tablet per day taken 10 days per month Duration is 6 months

Also known as: Provera

MPA 10 mg per oral cyclic for 6 months

Provera (medroxyprogesterone) DRUG

10 mg per oral tablet. One tablet per day for 6 months

Also known as: Provera

MPA 10 mg per os continuous 6 months

Mirena (levonorgestrel) DEVICE

Inserted in the uterine cavity and kept in situ for 6 months

Also known as: Mirena

LNG-IUD for 6 months

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• University Hospital of North Norway: lead
• Helse Nord: collaborator
• Norwegian Cancer Society: collaborator

Study Sites (1)

University Hospital of North Norway

Tromsø, Troms, 9038, Norway

Location

Related Publications (14)

• Kurman RJ, Kaminski PF, Norris HJ. The behavior of endometrial hyperplasia. A long-term study of "untreated" hyperplasia in 170 patients. Cancer. 1985 Jul 15;56(2):403-12. doi: 10.1002/1097-0142(19850715)56:23.0.co;2-x.

  PMID: 4005805 BACKGROUND

• Ferenczy A, Gelfand M. The biologic significance of cytologic atypia in progestogen-treated endometrial hyperplasia. Am J Obstet Gynecol. 1989 Jan;160(1):126-31. doi: 10.1016/0002-9378(89)90103-8.

  PMID: 2912075 BACKGROUND

• Orbo A, Baak JP, Kleivan I, Lysne S, Prytz PS, Broeckaert MA, Slappendel A, Tichelaar HJ. Computerised morphometrical analysis in endometrial hyperplasia for the prediction of cancer development. A long-term retrospective study from northern Norway. J Clin Pathol. 2000 Sep;53(9):697-703. doi: 10.1136/jcp.53.9.697.

  PMID: 11041060 BACKGROUND

• Vereide AB, Arnes M, Straume B, Maltau JM, Orbo A. Nuclear morphometric changes and therapy monitoring in patients with endometrial hyperplasia: a study comparing effects of intrauterine levonorgestrel and systemic medroxyprogesterone. Gynecol Oncol. 2003 Dec;91(3):526-33. doi: 10.1016/j.ygyno.2003.07.002.

  PMID: 14675671 BACKGROUND

• Nilsson CG, Haukkamaa M, Vierola H, Luukkainen T. Tissue concentrations of levonorgestrel in women using a levonorgestrel-releasing IUD. Clin Endocrinol (Oxf). 1982 Dec;17(6):529-36. doi: 10.1111/j.1365-2265.1982.tb01625.x.

  PMID: 6819901 BACKGROUND

• Scarselli G, Tantini C, Colafranceschi M, Taddei GL, Bargelli G, Venturini N, Branconi F. Levo-norgestrel-nova-T and precancerous lesions of the endometrium. Eur J Gynaecol Oncol. 1988;9(4):284-6.

  PMID: 3391204 BACKGROUND

• Orbo A, Arnes M, Hancke C, Vereide AB, Pettersen I, Larsen K. Treatment results of endometrial hyperplasia after prospective D-score classification: a follow-up study comparing effect of LNG-IUD and oral progestins versus observation only. Gynecol Oncol. 2008 Oct;111(1):68-73. doi: 10.1016/j.ygyno.2008.06.014. Epub 2008 Aug 6.

  PMID: 18684496 BACKGROUND

• Baak JP, Nauta JJ, Wisse-Brekelmans EC, Bezemer PD. Architectural and nuclear morphometrical features together are more important prognosticators in endometrial hyperplasias than nuclear morphometrical features alone. J Pathol. 1988 Apr;154(4):335-41. doi: 10.1002/path.1711540409.

  PMID: 3385513 BACKGROUND

• Perino A, Quartararo P, Catinella E, Genova G, Cittadini E. Treatment of endometrial hyperplasia with levonorgestrel releasing intrauterine devices. Acta Eur Fertil. 1987 Mar-Apr;18(2):137-40.

  PMID: 3115027 BACKGROUND

• Vereide AB, Kaino T, Sager G, Orbo A; Scottish Gynaecological Clinical Trials Group. Bcl-2, BAX, and apoptosis in endometrial hyperplasia after high dose gestagen therapy: a comparison of responses in patients treated with intrauterine levonorgestrel and systemic medroxyprogesterone. Gynecol Oncol. 2005 Jun;97(3):740-50. doi: 10.1016/j.ygyno.2005.02.030.

  PMID: 15885761 BACKGROUND

• Vereide AB, Kaino T, Sager G, Arnes M, Orbo A. Effect of levonorgestrel IUD and oral medroxyprogesterone acetate on glandular and stromal progesterone receptors (PRA and PRB), and estrogen receptors (ER-alpha and ER-beta) in human endometrial hyperplasia. Gynecol Oncol. 2006 May;101(2):214-23. doi: 10.1016/j.ygyno.2005.10.030. Epub 2005 Dec 1.

  PMID: 16325240 BACKGROUND

• Moe BT, Vereide AB, Orbo A, Jaeger R, Sager G. Levonorgestrel, medroxyprogesterone and progesterone cause a concentration-dependent reduction in endometrial cancer (Ishikawa) cell density, and high concentrations of progesterone and mifepristone act in synergy. Anticancer Res. 2009 Apr;29(4):1047-52.

  PMID: 19414344 BACKGROUND

• 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.

  PMID: 32909630 DERIVED

• Orbo A, Vereide A, Arnes M, Pettersen I, Straume B. Levonorgestrel-impregnated intrauterine device as treatment for endometrial hyperplasia: a national multicentre randomised trial. BJOG. 2014 Mar;121(4):477-86. doi: 10.1111/1471-0528.12499. Epub 2013 Nov 28.

  PMID: 24286192 DERIVED

MeSH Terms

Conditions

Endometrial Hyperplasia

Interventions

Medroxyprogesterone Acetate; Medroxyprogesterone; Progestins

Condition Hierarchy (Ancestors)

Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Hydroxyprogesterones; Progesterone; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Anne Ørbo, MD, PhD

  University of Tromso

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2010
• First Posted: February 24, 2010
• Study Start: May 1, 2005
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: April 5, 2019

Record last verified: 2012-05

Locations

NO (1)