NCT03118297

Intervention to End Recurrent Unscheduled Bleeding Trial

Intervention to End Recurrent Unscheduled Bleeding Trial: A Randomized-controlled Trial of Ulipristal Acetate for Unscheduled Bleeding in Etonogestrel Implant Users

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 65 (actual)
• Sponsor: Washington University School of Medicine · Academic / Other
• Sex: Female
• Age: 18 Years – 45 Years
• Healthy volunteers: Not accepted

Summary

The subdermal etonogestrel (ENG) implant, a long-acting reversible contraceptive (LARC) method, is among the most effective forms of reversible contraception and thus, an important tool in the quest to reduce unintended pregnancy. However, despite overall increases in LARC use in the United States from 1.5% in 2002 to 7.2% in 2011, and 11.6% most recently in 2015, implant use continues to make up a small proportion of LARC use. While evidence to explain this low uptake of implants is lacking, one potential reason is patient and provider concerns about unpredictable bleeding. As a result of this, many studies have been performed in attempts to discover therapies for unscheduled bleeding in progestin-only contraceptive users. Some of these studies include those investigating selective progesterone receptor modulators, such as mifepristone and ulipristal acetate (UPA), which did find some benefit. Although a previous study showed mixed benefit, the investigators feel that this medication has demonstrated both biologic plausibility as well as clinically important outcomes. This previous study may not be entirely translatable to the proposed research as therapies were used for different indications (prophylaxis vs. treatment) and different progestins and delivery systems were studied. Therefore, the investigators believe UPA should not be discounted as a potential therapy. UPA may provide an additional safe and effective option for treatment of irregular bleeding with implants in women. In addition, UPA is currently available in outpatient pharmacies in the U.S. as a single 30mg oral tablet. The investigators propose to investigate UPA for the treatment of unscheduled and troublesome bleeding in ENG implant users.

Detailed description

The subdermal etonogestrel (ENG) implant, a long-acting reversible contraceptive (LARC) method, is among the most effective forms of reversible contraception and thus, an important tool in the quest to reduce unintended pregnancy. Despite this, ENG implant users make up a small percent of overall women that use LARC in the United States. Previous studies have demonstrated that among women dissatisfied with their implant, the majority cite unpredictable and irregular bleeding as a primary reason. Dissatisfaction with a contraceptive method can lead to discontinuation, which can put a woman at risk for unplanned pregnancy. Although irregular bleeding is a common side effect of all progestin-only contraceptives, there are significant gaps in our knowledge regarding the etiology of and effective therapies for unscheduled bleeding. While several mechanisms have been proposed and therapies have been studied, lack of convincing scientific evidence, in addition to possible contraindications to these therapies, demonstrates the need to investigate additional effective interventions. Studies evaluating interventions for abnormal uterine bleeding resulting from uterine leiomyoma provide insight into potential therapies for progestin-mediated bleeding. In prior studies, ulipristal acetate (UPA) has been shown to reduce bleeding symptoms associated with uterine leiomyoma, including decreasing or stopping excessive bleeding. Progestin-associated irregular bleeding has been proposed to be secondary to a disruption in endometrial angiogenesis, therefore creating a fragile venous network. UPA may displace local progestin to counteract this effect. Thus, this medication has demonstrated both biologic plausibility as well as clinically important benefits. UPA may provide an additional safe and effective option for treatment of irregular bleeding in implant users. As women are often dissatisfied with irregular bleeding with the implant as noted above, improving bleeding profiles could potentially improve uptake and continuation of the device. The investigators will perform a double blinded, randomized, placebo-controlled trial. Women will be randomized to receive either 15mg of UPA daily for 7 days or placebo for the same duration. The investigators hypothesize that UPA will decrease bleeding and spotting days in users of the ENG implant with unscheduled bleeding when compared to placebo as assessed by daily bleeding diaries.

Conditions

• Contraception
• Bleeding

Interventions

Type	Name	Description
DRUG	Ulipristal Acetate	Women who have bothersome bleeding with the etonogestrel implant will be randomized to receive ulipristal acetate versus placebo daily for 7 days.
DRUG	Placebo oral capsule	Women who have bothersome bleeding with the etonogestrel implant will be randomized to receive ulipristal acetate versus placebo daily for 7 days.

Timeline

• Start date: 2017-05-01
• Primary completion: 2018-01-31
• Completion: 2018-01-31
• First posted: 2017-04-18
• Last updated: 2018-08-31
• Results posted: 2018-08-31

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study