Intervention to End Recurrent Unscheduled Bleeding Trial

NCT ID: NCT03118297

Last Updated: 2018-08-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-01
• Study Completion Date: 2018-01-31

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ulipristal Acetate

15mg ulipristal acetate (capsule) daily for 7 days

Group Type: EXPERIMENTAL

Ulipristal Acetate

Intervention Type: DRUG

Women who have bothersome bleeding with the etonogestrel implant will be randomized to receive ulipristal acetate versus placebo daily for 7 days.

Placebo

Identical placebo (capsule) daily for 7 days

Group Type: PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type: DRUG

Women who have bothersome bleeding with the etonogestrel implant will be randomized to receive ulipristal acetate versus placebo daily for 7 days.

Interventions

Ulipristal Acetate

Women who have bothersome bleeding with the etonogestrel implant will be randomized to receive ulipristal acetate versus placebo daily for 7 days.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Women age 18-45
• Implant placed >90 days and <3 years prior to enrollment
• Patient complaint of bothersome irregular bleeding with implant
• Willing to be abstinent or use condoms during study period
• Willing to complete 30-day bleeding diary
• Willing to be randomized to placebo or ulipristal acetate
• Ability to send/receive SMS text message

Exclusion Criteria

• Non-English speaking
• Implant placed >3 years prior to enrollment
• Contraindication to ulipristal acetate (current use of barbiturates, bosentan, carbamazepine, felbamate, griseofulvin, oxcarbazepine, phenytoin, rifampin, St. John's Wort, topiramate, known or suspected pregnancy, hypersensitivity to active substance or excipients, uterine/cervical/ovarian/breast cancer, severe asthma insufficiently controlled by oral glucocorticoids)
• Inability or unwillingness to comply with medication protocol
• Inability or unwillingness to comply with bleeding diary
• Breastfeeding

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Rachel Zigler, MD MSCI

Clinical Fellow

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rachel Zigler, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine in St. Louis

St Louis, Missouri, United States

Countries

United States

References

Zigler RE, Madden T, Ashby C, Wan L, McNicholas C. Ulipristal Acetate for Unscheduled Bleeding in Etonogestrel Implant Users: A Randomized Controlled Trial. Obstet Gynecol. 2018 Oct;132(4):888-894. doi: 10.1097/AOG.0000000000002810.

Reference Type: DERIVED

PMID: 30130351 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

201612002

Identifier Type: -

Identifier Source: org_study_id