Copper IUD Treatment Observation Study (CITROS)

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

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.

Study Overview

• Status: Completed
• Conditions: Menorrhagia
• Intervention / Treatment: Drug: Naproxen; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • John H Stroger Jr Hospital of Cook County
  • Washington
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98125
      • UW Neighborhood Clinic Northgate
    • Seattle, Washington, United States, 98195
      • Hall Health Center
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Centers

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 47 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	4 months

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: Teva Pharmaceuticals USA; Cook County Hospital
• Investigators: Principal Investigator: Emily Godfrey, MD,MPH, University of Washington

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Actual): November 1, 2017
• Study Completion (Actual): November 1, 2017

Study Registration Dates

• First Submitted: June 5, 2015
• First Submitted That Met QC Criteria: August 7, 2015
• First Posted (Estimate): August 10, 2015

Study Record Updates

• Last Update Posted (Actual): October 14, 2020
• Last Update Submitted That Met QC Criteria: September 23, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: bleeding; naproxen; IUD
• Additional Relevant MeSH Terms: Pathologic Processes; Uterine Diseases; Hemorrhage; Menstruation Disturbances; Uterine Hemorrhage; Menorrhagia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Gout Suppressants; Naproxen
• Other Study ID Numbers: STUDY00000323

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: All datasets used and analysed during the current study are available from the corresponding author on reasonable request
• IPD Sharing Time Frame: Until 12/2022
• IPD Sharing Supporting Information Type: Study Protocol; Informed Consent Form (ICF)