ContraceptionPhase 3INTERRUPTNCT03118297
Intervention to End Recurrent Unscheduled Bleeding Trial
A Phase 3 study testing Ulipristal Acetate in people with Contraception and Bleeding, run by Washington University School of Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Contraception, Bleeding
- What is being tested?
- Ulipristal Acetate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 65 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2017to 31 Jan 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine in St. Louis
St Louis, Missouri, 63110
About this study
Official title: 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.
Read the 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
- Being tested
- Ulipristal Acetate, Placebo oral capsule
- Keywords
- Etonogestrel Implant
- Medical subject headings
- Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ulipristal AcetateDrug
Women who have bothersome bleeding with the etonogestrel implant will be randomized to receive ulipristal acetate versus placebo daily for 7 days.
Placebo oral capsuleDrug
Women who have bothersome bleeding with the etonogestrel implant will be randomized to receive ulipristal acetate versus placebo daily for 7 days.
| Study group | Role | What they receive |
|---|---|---|
| Ulipristal Acetate | Experimental | 15mg ulipristal acetate (capsule) daily for 7 days Receives: Drug: Ulipristal Acetate |
| Placebo | Placebo comparator | Identical placebo (capsule) daily for 7 days Receives: Drug: Placebo oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Bleeding/Spotting Days With Use of Ulipristal Acetate as Measured by Daily Bleeding Diaries
To evaluate the effectiveness of ulipristal acetate (15mg) in decreasing bleeding/spotting days due to the ENG implant over a 30-day period as compared to placebo.
Measured: 30 days
Secondary outcomes (4)
Number of Participants With Bleeding Cessation by Day 10
To evaluate bleeding cessation rates by day 10 following seven days of treatment with either ulipristal acetate or placebo.
Measured: 10 days
Participant Satisfaction With Bleeding Pattern at 30 Days
To evaluate participant satisfaction with regards to bleeding pattern after use of ulipristal acetate.
Measured: 30 days
Number of Participants With Medication Side Effects by 30 Days
To evaluate participant satisfaction with regards to medication side effects.
Measured: 30 days
Ovulation Status Measured by Weekly Serum Progesterone Levels
To evaluate effect, if any, of ulipristal acetate on ovulation status. Data in the table represent the lowest and highest values that were recorded over all of the measurements for each arm as a whole.
Measured: Baseline, weeks 1, 2, 3, 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2017
- Study start1 May 2017
- Primary completion31 Jan 2018
- Study completion31 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ContraceptionStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rachel Zigler, MD MSCI, Washington University School of Medicine
- Investigators
- Rachel Zigler, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03118297
- Sponsor's protocol ID
- 201612002
- Acronym
- INTERRUPT
- Status last verified
- Aug 2018
- First submitted
- 4 Apr 2017
- Last updated
- 31 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 30130351
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intervention to End Recurrent Unscheduled Bleeding Trial: A Randomized-controlled Trial of Ulipristal Acetate for Unscheduled Bleeding in Etonogestrel Implant Users
- ClinicalTrials.gov ID
- NCT03118297
- Acronym / sponsor ID
- INTERRUPT / 201612002
- Conditions
- Contraception, Bleeding
- Keywords
- Etonogestrel Implant
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 1 May 2017 (actual)
- Primary completion
- 31 Jan 2018 (actual)
- Study completion
- 31 Jan 2018 (actual)
- First posted
- 18 Apr 2017 (actual)
- Results
- Posted 31 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ulipristal Acetate | Experimental | Drug: Ulipristal Acetate15mg ulipristal acetate (capsule) daily for 7 days |
| Placebo | Placebo comparator | Drug: Placebo oral capsuleIdentical placebo (capsule) daily for 7 days |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ulipristal AcetateWomen who have bothersome bleeding with the etonogestrel implant will be randomized to receive ulipristal acetate versus placebo daily for 7 days. | Drug | Ulipristal Acetate |
| Placebo oral capsuleWomen who have bothersome bleeding with the etonogestrel implant will be randomized to receive ulipristal acetate versus placebo daily for 7 days. | Drug | Placebo |
Primary outcome
Number of Bleeding/Spotting Days With Use of Ulipristal Acetate as Measured by Daily Bleeding Diaries
Time frame: 30 days
To evaluate the effectiveness of ulipristal acetate (15mg) in decreasing bleeding/spotting days due to the ENG implant over a 30-day period as compared to placebo.
4 secondary outcomes
Number of Participants With Bleeding Cessation by Day 10
Time frame: 10 days
Participant Satisfaction With Bleeding Pattern at 30 Days
Time frame: 30 days
Number of Participants With Medication Side Effects by 30 Days
Time frame: 30 days
Ovulation Status Measured by Weekly Serum Progesterone Levels
Time frame: Baseline, weeks 1, 2, 3, 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30130351Zigler 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rachel Zigler, MD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ulipristal Acetate in people with Contraception and Bleeding, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Bleeding/Spotting Days With Use of Ulipristal Acetate as Measured by Daily Bleeding Diaries (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03118297, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2018.