Intervention to End Recurrent Unscheduled Bleeding Trial
| Status: | Completed |
|---|---|
| Conditions: | Contraception, Contraception |
| Therapuetic Areas: | Reproductive |
| Healthy: | No |
| Age Range: | 18 - 45 |
| Updated: | 9/2/2018 |
| Start Date: | May 1, 2017 |
| End Date: | January 31, 2018 |
Intervention to End Recurrent Unscheduled Bleeding Trial: A Randomized-controlled Trial of Ulipristal Acetate for Unscheduled Bleeding in Etonogestrel Implant Users
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.
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.
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.
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.
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
We found this trial at
1
site
660 South Euclid Avenue
Saint Louis, Missouri 63110
Saint Louis, Missouri 63110
Phone: 314-747-6409
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