Abnormal Uterine Bleeding, Unspecified, Uterine Bleeding Heavy
Conditions
Keywords
etonogestrel implant, birth control, irregular bleeding, heavy bleeding
Brief summary
This double-blinded, placebo-controlled, randomized trial will compare the effects of the use of a combined oral contraceptive pill to a placebo pill for women who are experiencing irregular and/or heavy bleeding associated with the use of an etonogestrel (ETG) implant. The hypothesis of the study is: * Use of combined oral contraceptive will significantly improve bleeding patterns for users of ETG implant * Continuation rate of ETG implant users will be increased by use of combined oral contraceptive in women desiring ETG implant removal because of the undesirable bleeding * Adverse events will be uncommon and acceptable to women who use a combined oral contraceptive with the ETG implant
Detailed description
Women who are experiencing irregular and/or heavy bleeding associated with the use of an etonogestrel (ETG) implant will be recruited for this study. Women who have bothersome bleeding will be randomized to use either a combined oral contraceptive pill or a placebo pill. Participants will take one pill every day and record their bleeding patterns on a daily diary. Participants will have one screening/enrollment visit, two in-person follow up visits, and one telephone follow up contact. Subjects will be enrolled for a total of 84 days (three months). Participants will be assigned to a treatment group at her screening/enrollment visit. Her first follow up visit will occur 22-28 days after her enrollment. Participants can choose to: * Continue use of assigned treatment medication * Discontinue use of assigned treatment medication, but use an open-label combined oral contraceptive pill * Discontinue the use of assigned treatment medication, decline use of an open-label combined oral contraceptive pill * Discontinue use of ETG implant. Participants who choose to continue use of ETG implant will have a follow up telephone contact 50-56 days after her enrollment visit. A final in-person visit will occur 78-84 days after enrollment. Bleeding patterns will be assessed by daily bleeding diaries completed by the participant.
Interventions
DRUGEE 30mcg/LNG 150mcg
1 pill per day; daily during study participation (up to 84 days)
DRUGPlacebo
1 pill per day; daily during study participation (up to 84 days)
Sponsors
Washington University School of Medicine
University of California, Davis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
14 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women who have an ETG implant in place * Women who subjectively experience the side effect of an undesirable bleeding profile such as bleeding irregularity or heavy flow after ETG implant was placed and who desire intervention for this side effect by either treatment of bleeding or removal of the implant * Age 14 years an older, inclusive
Exclusion criteria
* Irregular or heavy bleeding from an etiology other than ETG use (e.g. fibroids, cervical polyp, or other organic cause of bleeding) * Has attempted prescription treatment for menstrual side effects while using ETG implant * Has one or more of the conditions considered Category 3 (risks outweigh benefits) or Category 4 (unacceptable health risk) for estrogen-containing oral contraceptives by the Center for Disease Control Medical Eligibility Criteria for Contraceptive Use: * Current or history of heart or vascular diseases, including deep venous thrombosis, pulmonary embolism, known thrombogenic mutations, peripartum cardiomyopathy, and complicated valvular heart disease * Hypertension, even if adequately controlled * Diabetes with vascular involvement * Headaches with focal aura, or migraines in women age 35 and older even without focal aura * Major surgery with prolonged immobilization * Breast cancer (current or past) * Severe (decompensated) cirrhosis * Acute or flare viral hepatitis * Breastfeeding less than 1 month postpartum * Post-partum less than 3 weeks * 35 years of age and older and smoking * Multiple risk factors for arterial cardiovascular disease * Systemic Lupus Erythematosus with positive or unknown antiphospholipid antibodies * Current symptomatic gallbladder disease or history of cholestasis related to past combined oral contraceptive use * On certain anticonvulsants (phenytoin, carbamazepine, barbiturates, primidone, topiramate, oxcarbazepine, lamotrigine) * On Ritonavir-boosted protease inhibitors for antiretroviral therapy * Issues or concerns, in the judgment of the investigator, that may compromise the safety of the subject, impact the subject's adherence to the protocol requirements, or confound the reliability of the data acquired in this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Bleeding Improvement | Bleeding improvement will be evaluated during first cycle of study treatment (28 days) | Bleeding improvement will be measured by participant response to the question of whether she feels her bleeding is improved and she is satisfied with the treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | Adverse events will be evaluated at each contact (visits at 1 and 3 months, phone contact at 2 months) with the participant | Participants will be evaluated for adverse events while using a combined oral contraceptive with ETG implant. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants withTreatment Success or Failure | Evaluated at follow up visits at 1 month and, if subject continues after 1st month, again at 3 months | Treatment success will be measured by desire to continue treatment because the initial treatment made the bleeding better. Partial failure of the study treatment will be measured by the desire to continue treatment because the initial treatment did not work Complete failure of treatment will be measured by the desire to: * discontinue treatment because it did not work; no further treatment requested * ETG implant removal * Desire to use non-study treatment |
| Bleeding Patterns and Number of Participants With Bleeding Improvement | Evaluated at follow up visits at 1 month and, if subject continues after 1st month, again at 3 months | * Bleeding improvement in women who received placebo but opted for open-label treatment after first cycle * Bleeding improvement over the 84 days of study participation * Bleeding patterns in placebo vs. combined oral contraceptive users |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| EE 30mcg/LNG 150mcg combined oral contraceptive pill: ethinyl estradiol (EE) 30mcg/levonorgestrel 150mcg); 1 pill per day; daily during study participation (up to 84 days)
EE 30mcg/LNG 150mcg: 1 pill per day; daily during study participation (up to 84 days) | 13 |
| Placebo Placebo
Placebo: 1 pill per day; daily during study participation (up to 84 days) | 13 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Implant removal | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 3 |
Baseline characteristics
| Characteristic | EE 30mcg/LNG 150mcg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 25.4 years STANDARD_DEVIATION 3.8 | 25.8 years STANDARD_DEVIATION 5 | 25.6 years STANDARD_DEVIATION 4.3 |
| Duration of implant use | 343 days | 109 days | 144.5 days |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 13 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| intervention requested before enrollment Hormonal treatment | 6 Participants | 4 Participants | 10 Participants |
| intervention requested before enrollment implant removal | 2 Participants | 3 Participants | 5 Participants |
| intervention requested before enrollment 'Some treatment' | 5 Participants | 6 Participants | 11 Participants |
| Primary reason for implant Bleeding Problem | 1 Participants | 1 Participants | 2 Participants |
| Primary reason for implant Contraception | 11 Participants | 12 Participants | 23 Participants |
| Primary reason for implant Dysmenorrhea | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 5 Participants | 5 Participants | 10 Participants |
| Region of Enrollment United States | 13 participants | 13 participants | 26 participants |
| Sex: Female, Male Female | 13 Participants | 13 Participants | 26 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 6 / 12 | 8 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Number of Participants With Bleeding Improvement
Bleeding improvement will be measured by participant response to the question of whether she feels her bleeding is improved and she is satisfied with the treatment.
Time frame: Bleeding improvement will be evaluated during first cycle of study treatment (28 days)
Population: 1 person in each group LTFU at one month, which was the primary outcome
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| EE 30mcg/LNG 150mcg | Number of Participants With Bleeding Improvement | No change | 0 Participants |
| EE 30mcg/LNG 150mcg | Number of Participants With Bleeding Improvement | Slightly worse | 0 Participants |
| EE 30mcg/LNG 150mcg | Number of Participants With Bleeding Improvement | Slight improvement | 1 Participants |
| EE 30mcg/LNG 150mcg | Number of Participants With Bleeding Improvement | Significantly worse | 0 Participants |
| EE 30mcg/LNG 150mcg | Number of Participants With Bleeding Improvement | Significant improvement | 11 Participants |
| Placebo | Number of Participants With Bleeding Improvement | Significantly worse | 0 Participants |
| Placebo | Number of Participants With Bleeding Improvement | Significant improvement | 5 Participants |
| Placebo | Number of Participants With Bleeding Improvement | Slight improvement | 3 Participants |
| Placebo | Number of Participants With Bleeding Improvement | Slightly worse | 2 Participants |
| Placebo | Number of Participants With Bleeding Improvement | No change | 2 Participants |
Secondary
Number of Participants With Adverse Events
Participants will be evaluated for adverse events while using a combined oral contraceptive with ETG implant.
Time frame: Adverse events will be evaluated at each contact (visits at 1 and 3 months, phone contact at 2 months) with the participant
Population: Outcomes at one month; 1 person LTFU at one month in each group
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| EE 30mcg/LNG 150mcg | Number of Participants With Adverse Events | Nausea/vomiting | 1 Participants |
| EE 30mcg/LNG 150mcg | Number of Participants With Adverse Events | Mood change | 0 Participants |
| EE 30mcg/LNG 150mcg | Number of Participants With Adverse Events | Cramping | 0 Participants |
| EE 30mcg/LNG 150mcg | Number of Participants With Adverse Events | None of above | 6 Participants |
| EE 30mcg/LNG 150mcg | Number of Participants With Adverse Events | Headache | 5 Participants |
| Placebo | Number of Participants With Adverse Events | None of above | 4 Participants |
| Placebo | Number of Participants With Adverse Events | Headache | 4 Participants |
| Placebo | Number of Participants With Adverse Events | Nausea/vomiting | 1 Participants |
| Placebo | Number of Participants With Adverse Events | Cramping | 2 Participants |
| Placebo | Number of Participants With Adverse Events | Mood change | 1 Participants |
Other Pre-specified
Bleeding Patterns and Number of Participants With Bleeding Improvement
* Bleeding improvement in women who received placebo but opted for open-label treatment after first cycle * Bleeding improvement over the 84 days of study participation * Bleeding patterns in placebo vs. combined oral contraceptive users
Time frame: Evaluated at follow up visits at 1 month and, if subject continues after 1st month, again at 3 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| EE 30mcg/LNG 150mcg | Bleeding Patterns and Number of Participants With Bleeding Improvement | Bleeding improvement | 12 Participants |
| EE 30mcg/LNG 150mcg | Bleeding Patterns and Number of Participants With Bleeding Improvement | No bleeding improvement | 4 Participants |
| Placebo | Bleeding Patterns and Number of Participants With Bleeding Improvement | Bleeding improvement | 5 Participants |
| Placebo | Bleeding Patterns and Number of Participants With Bleeding Improvement | No bleeding improvement | 0 Participants |
Other Pre-specified
Number of Participants withTreatment Success or Failure
Treatment success will be measured by desire to continue treatment because the initial treatment made the bleeding better. Partial failure of the study treatment will be measured by the desire to continue treatment because the initial treatment did not work Complete failure of treatment will be measured by the desire to: * discontinue treatment because it did not work; no further treatment requested * ETG implant removal * Desire to use non-study treatment
Time frame: Evaluated at follow up visits at 1 month and, if subject continues after 1st month, again at 3 months
Population: one month evaluation; 1 subject LTFU at one month in each group
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| EE 30mcg/LNG 150mcg | Number of Participants withTreatment Success or Failure | Continued assigned treatment | 8 Participants |
| EE 30mcg/LNG 150mcg | Number of Participants withTreatment Success or Failure | Desired COC prescription | 4 Participants |
| EE 30mcg/LNG 150mcg | Number of Participants withTreatment Success or Failure | Desired no treatment | 0 Participants |
| EE 30mcg/LNG 150mcg | Number of Participants withTreatment Success or Failure | Implant removal | 0 Participants |
| Placebo | Number of Participants withTreatment Success or Failure | Implant removal | 1 Participants |
| Placebo | Number of Participants withTreatment Success or Failure | Continued assigned treatment | 5 Participants |
| Placebo | Number of Participants withTreatment Success or Failure | Desired no treatment | 2 Participants |
| Placebo | Number of Participants withTreatment Success or Failure | Desired COC prescription | 4 Participants |