Menorrhagia
Conditions
Keywords
IUD, naproxen, bleeding
Brief summary
Studies indicate that bleeding irregularities and dysmenorrhea are common reasons for copper IUD method discontinuation. Some evidence suggests that non-steroidal anti-inflammatory medications (NSAIDs) can help improve bleeding during Cu-IUD use. However, these studies did not examine NSAID use with the TCu380A specifically, nor did they evaluate readily available NSAIDs such as over-the-counter naproxen. For this reason, the investigators propose a pilot trial in which new TCu380A users complaining of heavy or prolonged menstrual bleeding or spotting after 1 month of use are randomized to naproxen or placebo to be taken the first 7 days of menstruation for three consecutive cycles, and then observed for one cycle without treatment.
Detailed description
The Copper IUD (Cu-IUD) is the most widely used IUD in the world, and its use in the United States (US) is on the rise. The Cu-IUD is considered one of the most effective contraception methods, being as effective as permanent sterilization but having the convenience of being reversible should a woman decide to conceive.2 The Copper 380A (TCu380A) is the only Cu-IUD available in the US; of all Cu-IUDs, the TCu380A is considered the most effective. Despite its increasing popularity in the US, studies indicate that bleeding irregularities and dysmenorrhea are common reasons for method discontinuation. Some evidence suggests that non-steroidal anti-inflammatory medications (NSAIDs) can help improve bleeding during Cu-IUD use. However, these studies did not examine NSAID use with the TCu380A specifically, nor did they evaluate readily available NSAIDs such as over-the-counter naproxen. For this reason, the investigators propose a pilot trial in which new TCu380A users complaining of heavy or prolonged menstrual bleeding or spotting after 1 month of use are randomized to naproxen or placebo to be taken the first 7 days of menstruation for three consecutive cycles, and then observed for one cycle without treatment. The number of bleeding/spotting days will be compared using Student t-test. In addition to assessing how well naproxen reduces incidence and amount of bleeding, the investigators will also assess the use of naproxen and TCu380A on quality of life, sexual function, method satisfaction, menstrual pain, and adverse events. By measuring these variables, the investigators will assess both positive and negative consequences of TCu380A use, ensuring that harm does not outweigh benefits.
Interventions
DRUGNaproxen
Naproxen 440mg 1x pid
DRUGPlacebo
Placebo tablet 440mg 1x pid
Sponsors
Cook County Hospital
Teva Pharmaceuticals USA
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
* • Age ≥ 18 and \< 49 years. We are including a wide range of ages because women of all ages request TCu380A. While we recognize that some women approaching menopause (median age = 51.4 years) may have changes in their baseline menstruation, we trust that clinicians enrolling the patients into the study will ensure that these women meet all inclusion (i.e., regular cycles) and
Exclusion criteria
(i.e., do not have diagnosis of menorrhagia). * Requesting to have TCu380A IUD inserted as contraceptive method. * English-speaking. * Regular menstrual cycles ranging 21-35 days apart. * Generally healthy. * Willing to attend a 4- to 6-week follow-up visit and complete surveys.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Days of Bleeding and Spotting, Spotting Only and Bleeding Only for the 84 Day Treatment Cycles and Last 28 Day Post-treatment Cycle | 4 months | Number of bleeding and spotting, spotting only and bleeding only days given as mean. We calculated the mean difference and 95% confidence interval between the two treatment groups and provided the p-value of means. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | 4 months | Percentage reporting moderate-heavy/heavy menses, often/always menstrual cramping and 7 or more days of menstrual bleeding during the first 84 days and the last 28 days. We also report % difference and p-value between the two treatment groups. |
Countries
United States
Participant flow
Recruitment details
Between February 2016 to May 2017, 34 women enrolled into the study, of whom 28 were randomized.
Pre-assignment details
Subjects who completed the baseline questionnaires were contacted 4-5 weeks later to determine eligibility for randomization to a treatment arm. Participants were eligible to be randomized if they reported any change in menstrual bleeding since their TuC380A insertion, were willing to forgo NSAIDs, and willing to record their daily bleeding.
Participants by arm
| Arm | Count |
|---|---|
| Treatment This study arm includes naproxen as potential treatment for heavy or prolonged bleeding or dysmenorrhea may provide useful preliminary data for a larger, adequately powered placebo-controlled comparative trial testing additional promising treatments, such as tranexamic acid.
Naproxen: Naproxen 440mg 1x bid | 14 |
| Placebo This study arm includes capsules that are exactly like the active treatment medication (naproxen), but there is no active treatment medication in these tablets.
Placebo: Placebo tablet 1x bid | 14 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 5 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | Treatment |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 28 Participants | 14 Participants |
| Age, Continuous | 29.3 years | 29.3 years | 29.3 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 23 Participants | 12 Participants |
| Region of Enrollment United States | 14 participants | 28 participants | 14 participants |
| Sex: Female, Male Female | 14 Participants | 28 Participants | 14 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 / 13 | 0 / 14 |
| other Total, other adverse events | 0 / 13 | 0 / 14 |
| serious Total, serious adverse events | 0 / 13 | 0 / 14 |
Outcome results
Primary
Mean Days of Bleeding and Spotting, Spotting Only and Bleeding Only for the 84 Day Treatment Cycles and Last 28 Day Post-treatment Cycle
Number of bleeding and spotting, spotting only and bleeding only days given as mean. We calculated the mean difference and 95% confidence interval between the two treatment groups and provided the p-value of means.
Time frame: 4 months
Population: Population who submitted bleeding diaries at the end of the 6-month trial. We used intention-to-treat and included all data we had. We excluded missing data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Mean Days of Bleeding and Spotting, Spotting Only and Bleeding Only for the 84 Day Treatment Cycles and Last 28 Day Post-treatment Cycle | Bleeding or spotting days first 84 days | 29.2 days | Standard Error 4.5 |
| Treatment | Mean Days of Bleeding and Spotting, Spotting Only and Bleeding Only for the 84 Day Treatment Cycles and Last 28 Day Post-treatment Cycle | Bleeding only days last 28 days | 4.8 days | Standard Error 1 |
| Treatment | Mean Days of Bleeding and Spotting, Spotting Only and Bleeding Only for the 84 Day Treatment Cycles and Last 28 Day Post-treatment Cycle | Spotting only days first 84 days | 13.5 days | Standard Error 5.1 |
| Treatment | Mean Days of Bleeding and Spotting, Spotting Only and Bleeding Only for the 84 Day Treatment Cycles and Last 28 Day Post-treatment Cycle | Bleeding or spotting days last 28 days | 9.3 days | Standard Error 1.9 |
| Treatment | Mean Days of Bleeding and Spotting, Spotting Only and Bleeding Only for the 84 Day Treatment Cycles and Last 28 Day Post-treatment Cycle | Spotting only days last 28 days | 4.5 days | Standard Error 2 |
| Treatment | Mean Days of Bleeding and Spotting, Spotting Only and Bleeding Only for the 84 Day Treatment Cycles and Last 28 Day Post-treatment Cycle | Bleeding only days first 84 days | 15.7 days | Standard Error 2.1 |
| Placebo | Mean Days of Bleeding and Spotting, Spotting Only and Bleeding Only for the 84 Day Treatment Cycles and Last 28 Day Post-treatment Cycle | Spotting only days last 28 days | 3.0 days | Standard Error 0.8 |
| Placebo | Mean Days of Bleeding and Spotting, Spotting Only and Bleeding Only for the 84 Day Treatment Cycles and Last 28 Day Post-treatment Cycle | Bleeding only days last 28 days | 6.6 days | Standard Error 1.2 |
| Placebo | Mean Days of Bleeding and Spotting, Spotting Only and Bleeding Only for the 84 Day Treatment Cycles and Last 28 Day Post-treatment Cycle | Bleeding or spotting days last 28 days | 9.6 days | Standard Error 0.9 |
| Placebo | Mean Days of Bleeding and Spotting, Spotting Only and Bleeding Only for the 84 Day Treatment Cycles and Last 28 Day Post-treatment Cycle | Bleeding only days first 84 days | 15.5 days | Standard Error 1.8 |
| Placebo | Mean Days of Bleeding and Spotting, Spotting Only and Bleeding Only for the 84 Day Treatment Cycles and Last 28 Day Post-treatment Cycle | Spotting only days first 84 days | 7.5 days | Standard Error 1.7 |
| Placebo | Mean Days of Bleeding and Spotting, Spotting Only and Bleeding Only for the 84 Day Treatment Cycles and Last 28 Day Post-treatment Cycle | Bleeding or spotting days first 84 days | 23.0 days | Standard Error 2.8 |
Comparison: We originally planned to enroll 60 subjects based on other similar studies that evaluated treatment for bleeding among women using contraception; as reported by Cohen et al., a sample size of 42 provided 80% power to detect a difference of 7 bleeding/spotting days in 30 days by two-sample t-test, allowing for an expected 20% drop-out.p-value: 0.11t-test, 2 sided
Secondary
Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month
Percentage reporting moderate-heavy/heavy menses, often/always menstrual cramping and 7 or more days of menstrual bleeding during the first 84 days and the last 28 days. We also report % difference and p-value between the two treatment groups.
Time frame: 4 months
Population: Includes participants who responded to the monthly questionnaires, based on intention to treat analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 4 : Moderate heavy or heavy bleeding | 7 Participants |
| Treatment | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 1 : Often/always cramping | 1 Participants |
| Treatment | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 3 : Moderate heavy or heavy bleeding | 6 Participants |
| Treatment | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 1 : Unexpected bleeding | 6 Participants |
| Treatment | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 4 : Menstrual bleeding length 7+ days | 6 Participants |
| Treatment | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 2 : Moderate heavy or heavy bleeding | 4 Participants |
| Treatment | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 3 : Unexpected bleeding | 1 Participants |
| Treatment | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 2 : Menstrual bleeding length 7+ days | 8 Participants |
| Treatment | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 4 : Unexpected bleeding | 5 Participants |
| Treatment | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 2 : Often/always cramping | 1 Participants |
| Treatment | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 1 : Moderate heavy or heavy bleeding | 7 Participants |
| Treatment | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 2 : Unexpected bleeding | 7 Participants |
| Treatment | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 3 : Menstrual bleeding length 7+ days | 6 Participants |
| Treatment | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 4 : Often/always cramping | 3 Participants |
| Treatment | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 3 : Often/always cramping | 1 Participants |
| Treatment | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 1 : Menstrual bleeding length 7+ days | 8 Participants |
| Placebo | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 4 : Unexpected bleeding | 6 Participants |
| Placebo | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 3 : Moderate heavy or heavy bleeding | 7 Participants |
| Placebo | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 3 : Menstrual bleeding length 7+ days | 5 Participants |
| Placebo | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 3 : Often/always cramping | 1 Participants |
| Placebo | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 3 : Unexpected bleeding | 5 Participants |
| Placebo | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 4 : Moderate heavy or heavy bleeding | 5 Participants |
| Placebo | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 4 : Menstrual bleeding length 7+ days | 6 Participants |
| Placebo | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 1 : Moderate heavy or heavy bleeding | 7 Participants |
| Placebo | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 1 : Menstrual bleeding length 7+ days | 5 Participants |
| Placebo | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 1 : Often/always cramping | 5 Participants |
| Placebo | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 1 : Unexpected bleeding | 5 Participants |
| Placebo | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 2 : Moderate heavy or heavy bleeding | 8 Participants |
| Placebo | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 2 : Menstrual bleeding length 7+ days | 5 Participants |
| Placebo | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 2 : Often/always cramping | 1 Participants |
| Placebo | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 4 : Often/always cramping | 1 Participants |
| Placebo | Percentage Reporting Moderate-heavy/Heavy Menses, Often/Always Menstrual Cramping and 7 or More Days of Menstrual Bleeding for the 84-day Treatment Months and 28-day Post-treatment Month | Month 2 : Unexpected bleeding | 7 Participants |
p-value: <0.05Chi-squared