CITROS: Copper IUD Treatment Observation Study
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 4 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Active Comparator: 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. |
Drug: Naproxen
Naproxen 440mg 1x pid
Other Names:
|
Placebo Comparator: 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. |
Drug: Placebo
Placebo tablet 440mg 1x pid
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
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.
Exclusion Criteria:
-
Known or suspected pregnancy.
-
Contraindications to NSAID use. This includes underlying heart failure, chronic renal disease, chronic liver disease, peptic ulcer disease, or history of upper gastrointestinal bleed, and allergy to NSAIDs.
-
Current regular use of a NSAID.
-
Unwilling to avoid use of NSAIDs (except for study medication) for the duration of the study.
-
Current diagnosis of menorrhagia, metrorrhagia, symptomatic uterine fibroids, or endometrial polyps.
-
Use of depot medroxyprogesterone acetate (DMPA) or levonorgestrel-releasing intrauterine device (LNG IUD) within the previous 3 months.
-
Postpartum in the past 4 weeks. The average day in which non-breastfeeding postpartum women ovulate is 25 days after birth, indicating that menstrual cycles can resume after the 4th postpartum week.
-
Existing medical condition for which placement of TCu380A IUD is a contraindication according to the Centers for Disease Control and Prevention Medical Eligibility Criteria (MEC 4 medical conditions; see Appendix A).
-
Currently breastfeeding.
-
Previous use of the TCu380A.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | John H Stroger Jr Hospital of Cook County | Chicago | Illinois | United States | 60612 |
2 | Harborview Medical Center | Seattle | Washington | United States | 98104 |
3 | UW Neighborhood Clinic Northgate | Seattle | Washington | United States | 98125 |
4 | Hall Health Center | Seattle | Washington | United States | 98195 |
5 | University of Washington Medical Centers | Seattle | Washington | United States | 98195 |
Sponsors and Collaborators
- University of Washington
- Cook County Hospital
- Teva Pharmaceuticals USA
Investigators
- Principal Investigator: Emily Godfrey, MD,MPH, University of Washington
Study Documents (Full-Text)
More Information
Publications
None provided.- STUDY00000323
Study Results
Participant Flow
Recruitment Details | Between February 2016 to May 2017, 34 women enrolled into the study, of whom 28 were randomized. |
---|---|
Pre-assignment Detail | 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. |
Arm/Group Title | Treatment | Placebo |
---|---|---|
Arm/Group Description | 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 . Naproxen: Naproxen 440mg 1x bid for fist 7 days of menstrual cycle | 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 440mg 1x bid for first 7 days of menstruation |
Period Title: Overall Study | ||
STARTED | 14 | 14 |
COMPLETED | 12 | 8 |
NOT COMPLETED | 2 | 6 |
Baseline Characteristics
Arm/Group Title | Treatment | Placebo | Total |
---|---|---|---|
Arm/Group Description | 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 | 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 | Total of all reporting groups |
Overall Participants | 14 | 14 | 28 |
Age (Count of Participants) | |||
<=18 years |
0
0%
|
0
0%
|
0
0%
|
Between 18 and 65 years |
14
100%
|
14
100%
|
28
100%
|
>=65 years |
0
0%
|
0
0%
|
0
0%
|
Age (years) [Mean (Full Range) ] | |||
Mean (Full Range) [years] |
29.3
|
29.3
|
29.3
|
Sex: Female, Male (Count of Participants) | |||
Female |
14
100%
|
14
100%
|
28
100%
|
Male |
0
0%
|
0
0%
|
0
0%
|
Race (NIH/OMB) (Count of Participants) | |||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
Asian |
1
7.1%
|
2
14.3%
|
3
10.7%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
Black or African American |
0
0%
|
0
0%
|
0
0%
|
White |
12
85.7%
|
11
78.6%
|
23
82.1%
|
More than one race |
1
7.1%
|
1
7.1%
|
2
7.1%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Region of Enrollment (participants) [Number] | |||
United States |
14
100%
|
14
100%
|
28
100%
|
Outcome Measures
Title | Mean Days of Bleeding and Spotting, Spotting Only and Bleeding Only for the 84 Day Treatment Cycles and Last 28 Day Post-treatment Cycle |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Treatment | Placebo |
---|---|---|
Arm/Group Description | 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 . Naproxen: Naproxen 440mg 1x bid for fist 7 days of menstrual cycle | 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 440mg 1x bid for first 7 days of menstruation |
Measure Participants | 12 | 8 |
Bleeding or spotting days first 84 days |
29.2
(4.5)
|
23.0
(2.8)
|
Bleeding or spotting days last 28 days |
9.3
(1.9)
|
9.6
(0.9)
|
Bleeding only days first 84 days |
15.7
(2.1)
|
15.5
(1.8)
|
Bleeding only days last 28 days |
4.8
(1.0)
|
6.6
(1.2)
|
Spotting only days first 84 days |
13.5
(5.1)
|
7.5
(1.7)
|
Spotting only days last 28 days |
4.5
(2.0)
|
3.0
(0.8)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Treatment, Placebo |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | .11 |
Comments | The threshold for statistical significance was p =0.05 | |
Method | t-test, 2 sided | |
Comments | For days with bleeding/spotting outcomes, we used independent t-tests to compare the unadjusted mean difference between groups. | |
Method of Estimation | Estimation Parameter | Mean Difference (Net) |
Estimated Value | -1.76 | |
Confidence Interval |
(2-Sided) 95% to |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 5 |
|
Estimation Comments | Treatment Difference = Naproxen - Placebo | |
Other Statistical Analysis | We designed the study to include another site, in addition to the UW site enrolled participants. After 6 months of failed active recruitment at the other site, we discontinued that site from the study. Resources did not permit us to contract with an alternative recruitment site, and thus the protocol was revised to enroll 32 participants at the Seattle site only. |
Title | 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 |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
Includes participants who responded to the monthly questionnaires, based on intention to treat analysis. |
Arm/Group Title | Treatment | Placebo |
---|---|---|
Arm/Group Description | 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 pid | 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 440mg 1x pid |
Measure Participants | 13 | 14 |
Month 1 : Moderate heavy or heavy bleeding |
7
50%
|
7
50%
|
Month 1 : Menstrual bleeding length 7+ days |
8
57.1%
|
5
35.7%
|
Month 1 : Often/always cramping |
1
7.1%
|
5
35.7%
|
Month 1 : Unexpected bleeding |
6
42.9%
|
5
35.7%
|
Month 2 : Moderate heavy or heavy bleeding |
4
28.6%
|
8
57.1%
|
Month 2 : Menstrual bleeding length 7+ days |
8
57.1%
|
5
35.7%
|
Month 2 : Often/always cramping |
1
7.1%
|
1
7.1%
|
Month 2 : Unexpected bleeding |
7
50%
|
7
50%
|
Month 3 : Moderate heavy or heavy bleeding |
6
42.9%
|
7
50%
|
Month 3 : Menstrual bleeding length 7+ days |
6
42.9%
|
5
35.7%
|
Month 3 : Often/always cramping |
1
7.1%
|
1
7.1%
|
Month 3 : Unexpected bleeding |
1
7.1%
|
5
35.7%
|
Month 4 : Moderate heavy or heavy bleeding |
7
50%
|
5
35.7%
|
Month 4 : Menstrual bleeding length 7+ days |
6
42.9%
|
6
42.9%
|
Month 4 : Often/always cramping |
3
21.4%
|
1
7.1%
|
Month 4 : Unexpected bleeding |
5
35.7%
|
6
42.9%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Treatment, Placebo |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.05 |
Comments | ||
Method | Chi-squared | |
Comments |
Adverse Events
Time Frame | 4 months | |||
---|---|---|---|---|
Adverse Event Reporting Description | Daily diary asked patients to complete side effects while in study | |||
Arm/Group Title | Treatment | Placebo | ||
Arm/Group Description | 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 | 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 440mg 1x bid | ||
All Cause Mortality |
||||
Treatment | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/13 (0%) | 0/14 (0%) | ||
Serious Adverse Events |
||||
Treatment | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/13 (0%) | 0/14 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
Treatment | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/13 (0%) | 0/14 (0%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. If requested in writing, Institution and Investigator will withhold such Public Presentation for up to an additional ninety (90) days to allow for filing of a patent application.
Results Point of Contact
Name/Title | Dr. Emily Godfrey |
---|---|
Organization | University of Washington |
Phone | 206.685.4895 |
godfreye@uw.edu |
- STUDY00000323