Bleeding, Breakthrough Bleeding, Implants
Conditions
Keywords
Contraceptive implant, Irregular bleeding
Brief summary
The investigators plan to study the effects of curcumin, the active ingredient in the spice turmeric, on the irregular bleeding experienced by women who use the contraceptive implant.
Detailed description
The investigators are proposing a randomized, double blind placebo-controlled clinical trial over a 30-day reference period for treatment of women experiencing bothersome bleeding while using the etonogestrel (ENG) contraceptive implant. The primary outcome of the study will be the total number of amenorrhea days in a 30-day reference period. The study has a number of secondary outcomes (see study objectives) focused around the efficacy of oral curcumin to stop bleeding/spotting and for how long.
Interventions
DRUGPlacebo
Placebo (oral) once daily for 30 days. Treatment to be started after 3 consecutive days of bleeding
DRUGCurcumin
Curcumin 600 mg (oral) once daily for 30 days. Treatment to be started after 3 consecutive days of bleeding
Sponsors
Merck Sharp & Dohme LLC
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Placebo-controlled Computer-generated randomization schema
Eligibility
Sex/Gender
FEMALE
Age
15 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* English speaking * Women 15-45 years of age * Currently using the ENG implant for at least 30 days and use proven on exam (palpation of implant at screening visit) * Willing to continue using the implant for at least 30 days from study enrollment * \>7 days of continuous bleeding/spotting in the last 30 days, OR 2 or more episodes of bleeding/spotting in the last 30 days. * Access to a reliable cell phone and must be willing to receive and respond to a daily text or email message to assess bleeding and use of study drug * Negative gonorrhea/chlamydia screening performed at screening visit
Exclusion criteria
* Postpartum within six months * Post-abortion within six weeks * Currently pregnant * Currently breast-feeding (to be eligible, must be 4-6 weeks from cessation of breastfeeding) * Undiagnosed abnormal uterine bleeding pre-dating placement of contraceptive implant * Bleeding dyscrasia * Anticoagulation use * Active cervicitis * Allergy to curcumin or turmeric * History of venous thromboembolism * Current or past breast or uterine malignancy * Use of P450 pathway inducing drug * Implant is due to be switched out in 2 months or less from enrollment * Currently using oral contraceptives in addition to implant (to be eligible, needs to have a 4-6 week washout period) * Prior pregnancy occurred while Nexplanon/Implanon was in place
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Days Without Bleeding or Spotting | Day 1 to Day 30 | Total number of days without bleeding or spotting in the 30-day reference period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Bleeding/Spotting Days | Day 1 to Day 30 | Total number of days with bleeding or spotting in the 30-day reference period |
| Total Number of Spotting Days | Day 1 to Day 30 | Total number of days with spotting in the 30-day reference period |
| Total Number of Bleeding Days | Day 1 to Day 30 | Total number of days with bleeding in the 30-day reference period |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Patient Satisfaction With Bleeding Pattern as Assessed by VAS | Day 1 to Day 30 | Change in the level of patient satisfaction with bleeding pattern as measured by Visual Analog Scale (VAS) from Day 1 to Day 30. The scale ranges from 0 (lowest possible satisfaction) to 100 (highest possible satisfaction). |
| Proportion of Participants Who Intend to Continue Use of Implant | Day 30 | Percentage of participants who are continuing implant use or anticipate implant continuation, evaluated at the end of study |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Group Placebo (oral) once daily for 30 days to be started following 3 consecutive days of bleeding
Placebo: Placebo (oral) once daily for 30 days. Treatment to be started after 3 consecutive days of bleeding | 28 |
| Curcumin Group Curcumin 600 mg (oral) once daily for 30 days to be started following 3 consecutive days of bleeding
Curcumin: Curcumin 600 mg (oral) once daily for 30 days. Treatment to be started after 3 consecutive days of bleeding | 26 |
| Total | 54 |
Baseline characteristics
| Characteristic | Curcumin Group | Total | Placebo Group |
|---|---|---|---|
| Age, Continuous | 24 years STANDARD_DEVIATION 5.3 | 24 years STANDARD_DEVIATION 4.5 | 24 years STANDARD_DEVIATION 3.7 |
| Body mass index | 25 kg/m^2 STANDARD_DEVIATION 5.1 | 24 kg/m^2 STANDARD_DEVIATION 4.4 | 24 kg/m^2 STANDARD_DEVIATION 3.7 |
| Nulliparous | 23 Participants | 51 Participants | 28 Participants |
| Race/Ethnicity, Customized Race and Ethnicity Asian | 1 Participants | 4 Participants | 3 Participants |
| Race/Ethnicity, Customized Race and Ethnicity Hispanic/Latina | 8 Participants | 10 Participants | 2 Participants |
| Race/Ethnicity, Customized Race and Ethnicity More than one race | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Race and Ethnicity Native Hawaiian/Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race and Ethnicity White | 15 Participants | 36 Participants | 21 Participants |
| Region of Enrollment United States | 26 Participants | 54 Participants | 28 Participants |
| Sex: Female, Male Female | 26 Participants | 54 Participants | 28 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 / 29 | 0 / 29 |
| other Total, other adverse events | 1 / 29 | 2 / 29 |
| serious Total, serious adverse events | 0 / 29 | 0 / 29 |
Outcome results
Primary
Total Number of Days Without Bleeding or Spotting
Total number of days without bleeding or spotting in the 30-day reference period
Time frame: Day 1 to Day 30
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group | Total Number of Days Without Bleeding or Spotting | 17.5 days | Standard Deviation 4.8 |
| Curcumin Group | Total Number of Days Without Bleeding or Spotting | 16.7 days | Standard Deviation 6.9 |
Secondary
Total Number of Bleeding Days
Total number of days with bleeding in the 30-day reference period
Time frame: Day 1 to Day 30
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group | Total Number of Bleeding Days | 7.6 days | Standard Deviation 4.5 |
| Curcumin Group | Total Number of Bleeding Days | 6.6 days | Standard Deviation 4.9 |
Secondary
Total Number of Bleeding/Spotting Days
Total number of days with bleeding or spotting in the 30-day reference period
Time frame: Day 1 to Day 30
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group | Total Number of Bleeding/Spotting Days | 12.5 days | Standard Deviation 4.8 |
| Curcumin Group | Total Number of Bleeding/Spotting Days | 13.3 days | Standard Deviation 6.9 |
Secondary
Total Number of Spotting Days
Total number of days with spotting in the 30-day reference period
Time frame: Day 1 to Day 30
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group | Total Number of Spotting Days | 4.9 days | Standard Deviation 3.1 |
| Curcumin Group | Total Number of Spotting Days | 6.7 days | Standard Deviation 4.3 |
Other Pre-specified
Change in Patient Satisfaction With Bleeding Pattern as Assessed by VAS
Change in the level of patient satisfaction with bleeding pattern as measured by Visual Analog Scale (VAS) from Day 1 to Day 30. The scale ranges from 0 (lowest possible satisfaction) to 100 (highest possible satisfaction).
Time frame: Day 1 to Day 30
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Group | Change in Patient Satisfaction With Bleeding Pattern as Assessed by VAS | 9.5 units on a scale |
| Curcumin Group | Change in Patient Satisfaction With Bleeding Pattern as Assessed by VAS | 42 units on a scale |
Other Pre-specified
Proportion of Participants Who Intend to Continue Use of Implant
Percentage of participants who are continuing implant use or anticipate implant continuation, evaluated at the end of study
Time frame: Day 30
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo Group | Proportion of Participants Who Intend to Continue Use of Implant | 23 Participants |
| Curcumin Group | Proportion of Participants Who Intend to Continue Use of Implant | 16 Participants |