Treatment of Prolonged Uterine Bleeding of Etonogestrel (ENG)-Releasing Implant Using Norethisterone (NET)-Only Pill: a Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Percentage of women who will stop the prolonged uterine bleeding after 7 days of medication use.
研究概览
简要总结
Long-acting reversible contraceptives [LARC; copper-intrauterine devices (IUDs), the levonorgestrel-releasing intrauterine system (LNG-IUS) and subdermal implants] are the most effective reversible contraceptives available. A common side effect of these methods is changes in menstrual bleeding. Dissatisfaction with unpredictable bleeding is the main reason for early discontinuation of LARC methods.
The mechanism of unpredictable bleeding is unknown; it is likely related to the progestogen dilating superficial veins and capillaries, which are fragile and susceptible to focal bleeding. Other potential influences include changes in structural support of the endometrium, altered matrix metalloproteinase activity, and changes in endometrial perfusion and hemostasis. Local genetic alterations of the hormonal receptors of endometrium can also play a role in the etiology of the unpredictable bleeding experienced by some women.
Regarding etonogestrel (ENG)-releasing implant, some evidences suggest that the use of mefenamic acid, mifepristone with estradiol or doxycycline, or doxycycline alone can temporally stop the bleeding; however, all these therapies cannot avert the recurrence of the bleeding. Recently, a randomized clinical trial (RCT) evaluated the effectiveness of a short-term use of combined oral contraceptive (COC) in stopping bleeding episodes and preventing bleeding recurrence. The authors found that bothersome bleeding in ENG-implant users stopped within 14-day of COC treatment, but bleeding most often resumes within 10 days of treatment cessation.
Although COC can stop the bleeding, it is not known which component of the COC is responsible for this effect. There is evidence suggesting that estrogen alone is not effective in stopping the bleeding of progestogen-only contraceptives or a high dose of ethinyl estradiol is needed to obtain this effect. Furthermore, the recurrence of the bleeding shown with the COC use could be explained by the interruption of the estrogen. For this reason, our hypothesis is that a progestogen-only pill could be superior to placebo in stopping the bleeding associated with the ENG-implant use as well as being superior to placebo in recurrence of bleeding after discontinuation of the therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •To be an etonogestrel-releasing implant user for at least 40 days who reports at least one previous prolonged uterine bleeding episode (≥ 10 days of consecutive uterine bleeding) with a current bleeding/spotting episode of at least 7 consecutive days;
- •Age between 18-40 years old;
- •To have a mobile phone.
排除标准
- •Body mass index (BMI; kg/m2) ≥ 35;
- •Pregnancy;
- •To have a positive chlamydia test;
- •To be unable or unwilling to swallow pills;
- •To have a medical condition deemed severe by a physician investigator;
- •To be in use of a hepatic enzyme inducing medication;
- •To be in use of anticoagulant drug;
- •To have findings on speculum examination indicating an anatomic source of bleeding (e.g., polyp, cervicitis);
- •To be in the first 6 months of delivery;
- •To be on a concurrent hormonal contraceptive, depot medroxyprogesterone acetate (DMPA) interruption ≤ 6 months;
- •To be illiterate;
- •To be in use of any drug to stop the bleeding associated with etonogestrel implant ≤ 15 days.
研究组 & 干预措施
Norethisterone 10mg/day
NET-only pill (Norethisterone, Primolut-Nor®), 10 mg/day, 1 pill per day until 2 consecutive days without bleeding/spotting (maximum use of 1 box of Primolut-Nor® per bleeding episode)
干预措施: Norethisterone 10mg/day (Drug)
Placebo
Identically appearing placebo to Primolut-Nor®, 1 pill per day until 2 consecutive days without bleeding/spotting (maximum use of 1 box of Placebo per bleeding episode)
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of women who will stop the prolonged uterine bleeding after 7 days of medication use.
时间窗: 7 days
We will measure the percentage of women will stop the uterine bleeding after 7 days of norethisterone or placebo use. Participants will report their bleeding and/or spotting through text messages and daily diary.
次要结局
- Number of days of medication use until interruption of uterine bleeding episode(30 days)
- Percentage of women who will stop the prolonged uterine bleeding after 14 days of medication use.(14 days)
- The interval (number of days) to the recurrence of uterine bleeding after discontinuation of the first treatment cycle.(6 months)
- Bleeding patterns within 6 months after the end of the first treatment cycle(6 months)
- Percentage of women who will need to repeat the treatment in order to stop the uterine bleeding (none vs. 1-2 times vs. 3 times)(6 months)
- Relation between plasmatic levels of etonogestrel and bleeding patterns at baseline and at 7 days of randomized drug use(7 days)
- Treatment failure(30 days)
研究者
Carolina Sales Vieira
Professor, MD, PhD
University of Sao Paulo