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Ulipristal Versus Placebo for Women With Bleeding Induced by Mirena

Phase 4
Conditions
Heavy Menstrual Bleeding
Abnormal Bleeding
Interventions
Registration Number
NCT03186586
Lead Sponsor
University of Campinas, Brazil
Brief Summary

Objectives: To assess if the administration of ulipristal acetate (UPA) in users of the levonorgestrel-releasing intrauterine system (LNG-IUS) with breakdown bleeding or abnormal bleeding, could be able to inhibit the bleeding and if this effect will be sustainable up to three months after treatment.

Material and methods: A total of 32 women aged between 18-45 years, users of the LNG-IUS with breakdown bleeding, abnormal bleeding or prolonged bleeding (bleeding more than 14 days) or episodes of bleeding with intervals less than 24 days). The study is an experimental, double blind randomized (16 women will receive UPA 5 mg/day/5 days; 16 women will receive placebo/1 time/day/5 day). The women will invited to participated at the Family Planning clinic at the day they consulted with the complaint of bleeding. That day they will allocated at random to UPA or placebo group. They will oriented to fill out a bleeding calendar through 90 days after the pill intake. In addition a ultrasonography scan will be perform before the first day of pill intake and at 90 days after.

Statistical analysis: A a pilot study the sample was estimated in 26 women (13 at each group) based at the estimative of success of 0.95 with UPA and 0.35 with placebo with significance of 0.05 and power of 80%. The sociodemographic characteristics will be analyzed as mean and SD and will compared through Mann-Whitney, Yates χ2 and Fisher exact tests as apropriate. Also, a regression analysis (Poisson analysis) with the dependent significant variables. The established level of significance will be p \< 0.05.

Detailed Description

The LNG-IUS is a contraceptive method with high efficacy, long acting, reversible with contraceptive failure between 0.1 and 0.5/100 women/year. It released 20 mcg/day of LNG with a life span duration of 5 years. LNG is a synthetic progestin, 19-northestosterone, six times more potent than progesterone, with androgenic properties and with binding with sexual hormones, receptors of human steroids, including receptors of glucocorticoids and mineralocorticoids, with minimal capacity of binding with estrogen receptors. At endometrium level it induce antiproliferative effect and strong expression of local markers and endometrial decidualization, including the prolactin receptor and insulin-like growth factor. The mechanism of action includes effect upon cervical mucus which affects the sperm movements through the reproductive tract which affects fertilization. In some women could be ovulation inhibition. One of the main reason for discontinuation is breakdown bleeding, increase bleeding or abnormal bleeding including heavy menstrual bleeding (HMB) and spotting which is common at the first six month of use. Despite the fact that it is the main cause of discontinuation, there is no effective treatment for these cases. An effective treatment could help in the reduction of reduce the rates of discontinuation, improved the cost-effectiveness and quality of life of users.

A selective progesterone receptor modulator (SPRM) is Ulipristal Acetate (UPA) is approved in the European Union as Esmya® as a tretament to reduce the ueterine leiomyomas at te dose of 5 mg/day and it under evaluation at the dose of 5-10 mg as oral contraceptive.

This could be an option of treatment for HMB or abnormal bleeding induced by the LNG-IUS. UPA is agonist/antagonist and binding with progesterone to the receptor level. It has ovarian and endometrial activity, with dose-dependent effect in inhibition of ovulation and maturation of the endometrium. There are restricted evidences, that the administration of UPA induce a quick endometrial atrophy and stop the abnormal bleeding.

Recruitment & Eligibility

Status
UNKNOWN
Sex
Female
Target Recruitment
32
Inclusion Criteria

Women with complaints of abnormal bleeding during use of Mirena independently of the length of use

Exclusion Criteria

Delivery in the last six months Breastfeeding Hematological disorder Use of anticoagulants Uterine leiomioma

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo 1 pill/day/five daysPlaceboWomen with abnormal bleeding during use of Mirena will allocate to UPA or placebo Placebo at 1pill/day/five days Placebo one pill a day for 5 days at the bleeding episode
Ulipristal acetate 5mg/day/five daysUlipristal acetateWomen with abnormal bleeding during use of Mirena will allocate to UPA or placebo Ulipristal acetate at 5mg/day/five days Ulipristal 5mg daily for 5 days at the bleeding episode
Primary Outcome Measures
NameTimeMethod
Uterine bleeding control (stop bleeding)Three months

Uterine bleeding control (stop bleeding) among users of Mirena after use of UPA or placebo

Secondary Outcome Measures
NameTimeMethod
Endometrial controlThree months

Endometrial thickness

Trial Locations

Locations (1)

University of Campinas

🇧🇷

Campinas, SP, Brazil

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