CITROS: Copper IUD Treatment Observation Study

Sponsor
University of Washington (Other)
Overall Status
Completed
CT.gov ID
NCT02519231
Collaborator
Cook County Hospital (Other), Teva Pharmaceuticals USA (Industry)
34
5
2
21
6.8
0.3

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

Study Type:
Interventional
Actual Enrollment :
34 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Multi-Center, Double-Blinded, Randomized, Phase IV 6-Month Pilot Study to Compare Bleeding Patterns, Satisfaction and Quality of Life Among New Copper 380A IUD Users Treated With Naproxen Sodium (440mg Twice Daily) Versus Placebo
Study Start Date :
Feb 1, 2016
Actual Primary Completion Date :
Nov 1, 2017
Actual Study Completion Date :
Nov 1, 2017

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:
  • Intervention
  • 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:
  • Control
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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

    Ages Eligible for Study:
    18 Years to 49 Years
    Sexes Eligible for Study:
    Female
    Accepts 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.

    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.
    Responsible Party:
    Emily Godfrey, Associate Professor of Family Medicine and OB/GYN, University of Washington
    ClinicalTrials.gov Identifier:
    NCT02519231
    Other Study ID Numbers:
    • STUDY00000323
    First Posted:
    Aug 10, 2015
    Last Update Posted:
    Oct 14, 2020
    Last Verified:
    Sep 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by Emily Godfrey, Associate Professor of Family Medicine and OB/GYN, University of Washington
    Additional relevant MeSH terms:

    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

    1. Primary Outcome
    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.
    2. Secondary Outcome
    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

    (1) Small sample size, which did not provide sufficient power to detect differences between the groups; (2) Missing bleeding diaries of 40% of placebo users and 15% of naproxen users. Our findings should be interpreted with caution.

    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
    Email godfreye@uw.edu
    Responsible Party:
    Emily Godfrey, Associate Professor of Family Medicine and OB/GYN, University of Washington
    ClinicalTrials.gov Identifier:
    NCT02519231
    Other Study ID Numbers:
    • STUDY00000323
    First Posted:
    Aug 10, 2015
    Last Update Posted:
    Oct 14, 2020
    Last Verified:
    Sep 1, 2020