Compare Two Copper IUDs: Mona Lisa NT Cu380 Mini and ParaGard

A Multi-center, Single-blind, Randomized Clinical Trial to Compare Two Copper IUDs: Mona Lisa NT Cu380 Mini and ParaGard

This will be a multi-site, participant-blinded, randomized clinical trial. The investigators will randomize 1000 eligible participants in a 4:1 ratio to two different copper IUDs: 800 to Mona Lisa NT Cu380 Mini and 200 to ParaGard.

Study Overview

• Status: Completed
• Conditions: Female Contraception; Healthy Women
• Intervention / Treatment: Drug: Mona Lisa® NT Cu380 Mini; Drug: ParaGard® TCu380A

Detailed Description

The total duration of the study for each participant is expected to be approximately 39 months: including screening and enrollment (up to 30 days to meet enrollment criteria), 37 months of participation, and a post-removal follow up telephone call 17 days post-removal. After enrollment, subject visits occur at 6 weeks, 3 months, 6 months, 12 months, 24 months, with telephone calls at 9, 18, and 30 months and seen again at 37 months for their final visit. Subjects will use a home pregnancy test 17 days post-removal of the IUD or Exit Visit procedures, whichever occurs first, and called by the site for the result and for safety follow-up.

Subject recruitment is expected to begin Q2 (in the second quarter of) 2017 and is planned to continue through Q2 2018. However, if the enrollment rate declines, the enrollment period may be extended beyond this date. If this enrollment timeline is met, all subjects should finish active treatment by approximately the end of Q2 2021. The total duration of the study will be approximately 48 months for each study site including pre- and post- trial activities. The end of the study will occur when the last subject to be enrolled has completed her post-removal pregnancy test telephone call.

Total duration of the project is expected to be five years. Preliminary results of the study are expected to be available Q4 of 2019 based on the current study plan.

• Study Type: Interventional
• Enrollment (Actual): 1105
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90010
      • Essential Access Health
    • Sacramento, California, United States, 95817
      • University of California, Davis
    • San Francisco, California, United States, 94110
      • University of California, San Francisco
  • Colorado
    • Denver, Colorado, United States, 80045
      • University of Colorado
  • Hawaii
    • Honolulu, Hawaii, United States, 96826
      • University of Hawaii
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Planned Parenthood League of Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center Corporation
  • New York
    • New York, New York, United States, 10032
      • Columbia University
    • New York, New York, United States, 10012
      • Planned Parenthood of New York
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • University of Utah
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Eastern Virginia Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 40 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 16-40 years

  o 16 and 17 year olds, where permissible by state regulations and local Institutional Review Board (IRB) approval

• Sexually active, anticipating at least one act of vaginal intercourse per menstrual cycle with a male partner and at risk for pregnancy
• seeking contraception, and willing to use the study IUD as the only contraception method
• willing to be randomized to one of the two copper IUDs
• has an intact uterus and at least one ovary
• has a history of regular menstrual cycles; defined as occurring every 21-35 days when not using hormones, and with a variation of typical cycle length of no more than 5 days
• able and willing to provide written informed consent
• agrees to follow all study requirements
• not currently pregnant or at risk for luteal phase pregnancy based on history of unprotected intercourse

Exclusion Criteria:

• abnormal Pap requiring treatment after enrollment
• known human immunodeficiency virus / acquired immunodeficiency syndrome (HIV/AIDS) infection
• intending to become pregnant in the 37 months after enrollment
• known infertility
• history of allergy or sensitivity to copper
• previous tubal sterilization
• has received an injectable contraceptive in the last 9 months and has not resumed regular menstrual cycles (as evidenced by 2 spontaneous menses)
• within 30 days of administration of mifepristone and/or misoprostol for medical abortion or for miscarriage management
• within 30 days of first, second, or third trimester abortion or miscarriage (note: potential abortion/miscarriage participants can be screened and return after 30 days for randomization and IUD insertion)
• within 30 days of delivery (for parous population)
• breastfeeding or recently breastfeeding women unless two consecutive normal menstrual periods have occurred after delivery and prior to enrollment.
• wants to use a copper IUD for emergency contraception
• has previously participated in the study
• participated in another clinical trial involving an investigational product within the last 30 days (before screening) or planning to participate in another clinical trial involving an intervention or treatment during this study
• not living in the catchment area of the study site or planning to move from the area within the year (unless known to be moving to the catchment area of another study site)
• known or suspected current alcohol or drug abuse
• planning to undergo major surgery during study participation
• current need for use of exogenous hormones or therapeutic anticoagulants (Note: subjects who start a therapeutic anticoagulant after enrolment will be allowed to continue in the study.)
• at high risk for sexually-transmitted infections or pelvic infection
• anticipated need for regular condom use (refer to Section 8.1).
• has any condition (social or medical) which in the opinion of the Investigator would make study participation unsafe or complicate data interpretation

• Reported medical contraindications (Medical Eligibility Criteria category 3 or 4)14 to copper IUDs, including:

  • suspicious unexplained vaginal bleeding
  • known cervical cancer
  • known endometrial cancer
  • known Wilson's disease
  • Confirmed gestational trophoblastic disease with persistently elevated beta-hCG levels or malignant disease, with evidence or suspicion of intrauterine disease
  • anatomic abnormalities with distorted uterine cavity
  • current pelvic inflammatory disease (PID)
  • pelvic tuberculosis
  • immediately post-septic abortion or puerperal sepsis
  • current known purulent cervicitis or chlamydial infection or gonorrhea; Note: to enroll, there must be no obvious signs of infection at the time of enrollment based on pelvic exam. If lab results come back for positive infection after enrollment, treatment should be provided but the IUD can be left in place.
  • complicated solid organ transplantation
  • systemic lupus erythematosus with severe thrombocytopenia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mona Lisa® NT Cu380 Mini; Mona Lisa® NT Cu380 Mini containing 380mm2 of copper surface inserted into the uterine cavity.	Drug: Mona Lisa® NT Cu380 Mini; copper intrauterine device; Other Names: NT380-Mini, NTCu380-Mini
Active Comparator: ParaGard® TCu380A; ParaGard® TCU380A containing 380mm2 of copper surface inserted into the uterine cavity.	Drug: ParaGard® TCu380A; copper intrauterine device; Other Names: T380

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pregnancy Rate of Mona Lisa Copper IUD Over 3 Years	Pearl Index is a measure of contraceptive efficacy used by the FDA that summarizes number of method failures per 100 person years	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IUD Continuation	IUD continuation at 36-months by product	3 years
Failed IUD Insertion	Failed IUD insertion as measured by inability to place the IUD correctly	Immediate after IUD insertion attempt
Uterine Perforation	Uterine perforation as measured by ultrasound	3 years
IUD Expulsion (Complete and Partial)	When the IUD is expelled from the uterus, either completely or partially.	3 years
Vaginal Bleeding Patterns	Proportion of cycles with heavy bleeding (more than 4 sanitary products in a day)	1 year
Pelvic Pain as Measured in the Subject Diary	Percent of cycles with any pelvic pain will be calculated using all available cycles	1 year
Dysmenorrhea	Number of participants who experienced any dysmenorrhea during the trial	3 years
Pain With and Shortly After Insertion as Recorded by Study Subjects	Pain level on scale of 0=no pain to 10=worst imaginable pain as displayed on a paper form for study subject to indicate their level of pain	Pain level 10 minutes after IUD insertion
Ease of IUD Insertion as Recorded by the Investigator	Investigator to assess ease of IUD insertion (easy, somewhat easy, somewhat hard or hard)	Right after IUD insertion
Overall Product Satisfaction as Measured by Acceptability Questions Asked of Subjects	Overall product satisfaction level at exit visit (highly satisfied, satisfied, dissatisfied, highly dissatisfied)	3 years

Collaborators and Investigators

• Sponsor: FHI 360
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Health Decisions
• Investigators: Study Director: Diana Blithe, National Institute of Child Health & Human Development (NICHD); Study Director: David Hubacher, FHI 360

Publications and helpful links

General Publications

• Committee on Adolescent Health Care Long-Acting Reversible Contraception Working Group, The American College of Obstetricians and Gynecologists. Committee opinion no. 539: adolescents and long-acting reversible contraception: implants and intrauterine devices. Obstet Gynecol. 2012 Oct;120(4):983-8. doi: 10.1097/AOG.0b013e3182723b7d.
• Heinemann K, Reed S, Moehner S, Minh TD. Risk of uterine perforation with levonorgestrel-releasing and copper intrauterine devices in the European Active Surveillance Study on Intrauterine Devices. Contraception. 2015 Apr;91(4):274-9. doi: 10.1016/j.contraception.2015.01.007. Epub 2015 Jan 16.
• The TCu380A, TCu220C, multiload 250 and Nova T IUDS at 3,5 and 7 years of use--results from three randomized multicentre trials. World Health Organization. Special Programme of Research, Development and Research Training in Human Reproduction: Task Force on the Safety and Efficacy of Fertility Regulating Methods. Contraception. 1990 Aug;42(2):141-58.
• Sivin I, Stern J. Long-acting, more effective copper T IUDs: a summary of U.S. experience, 1970-75. Stud Fam Plann. 1979 Oct;10(10):263-81. No abstract available.
• Sivin I, Tatum HJ. Four years of experience with the TCu 380A intrauterine contraceptive device. Fertil Steril. 1981 Aug;36(2):159-63.
• Sivin I, Stern J, Coutinho E, Mattos CE, el Mahgoub S, Diaz S, Pavez M, Alvarez F, Brache V, Thevenin F, et al. Prolonged intrauterine contraception: a seven-year randomized study of the levonorgestrel 20 mcg/day (LNg 20) and the Copper T380 Ag IUDS. Contraception. 1991 Nov;44(5):473-80. doi: 10.1016/0010-7824(91)90149-a.
• Hubacher D. Copper intrauterine device use by nulliparous women: review of side effects. Contraception. 2007 Jun;75(6 Suppl):S8-11. doi: 10.1016/j.contraception.2006.12.005. Epub 2007 Feb 20.
• Abraham M, Zhao Q, Peipert JF. Young Age, Nulliparity, and Continuation of Long-Acting Reversible Contraceptive Methods. Obstet Gynecol. 2015 Oct;126(4):823-829. doi: 10.1097/AOG.0000000000001036.
• Benacerraf BR, Shipp TD, Lyons JG, Bromley B. Width of the normal uterine cavity in premenopausal women and effect of parity. Obstet Gynecol. 2010 Aug;116(2 Pt 1):305-310. doi: 10.1097/AOG.0b013e3181e6cc10.
• Koch P, Reinhardt P, Soyka E. Intrauterine contraception using the Copper Mini-Gravigard 7 IUD: summary of 328 case histories. Contracept Deliv Syst. 1981 Apr;2(1):171-6.
• Petersen KR, Brooks L, Jacobsen N, Skoby SO. Clinical performance of intrauterine devices in nulligravidae: is the length of the endometrial cavity of significance? Acta Eur Fertil. 1991 Jul-Aug;22(4):225-8.
• Otero-Flores JB, Guerrero-Carreno FJ, Vazquez-Estrada LA. A comparative randomized study of three different IUDs in nulliparous Mexican women. Contraception. 2003 Apr;67(4):273-6. doi: 10.1016/s0010-7824(02)00519-x.
• Ott MA, Sucato GS; Committee on Adolescence. Contraception for adolescents. Pediatrics. 2014 Oct;134(4):e1257-81. doi: 10.1542/peds.2014-2300.
• Curtis KM, Tepper NK, Jatlaoui TC, Berry-Bibee E, Horton LG, Zapata LB, Simmons KB, Pagano HP, Jamieson DJ, Whiteman MK. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep. 2016 Jul 29;65(3):1-103. doi: 10.15585/mmwr.rr6503a1.
• Farley TM, Rosenberg MJ, Rowe PJ, Chen JH, Meirik O. Intrauterine devices and pelvic inflammatory disease: an international perspective. Lancet. 1992 Mar 28;339(8796):785-8. doi: 10.1016/0140-6736(92)91904-m.
• Hubacher D, Schreiber CA, Turok DK, Jensen JT, Creinin MD, Nanda K, White KO, Dayananda I, Teal SB, Chen PL, Chen BA, Goldberg AB, Kerns JL, Dart C, Nelson AL, Thomas MA, Archer DF, Brown JE, Castano PM, Burke AE, Kaneshiro B, Blithe DL. Continuation rates of two different-sized copper intrauterine devices among nulliparous women: Interim 12-month results of a single-blind, randomised, multicentre trial. EClinicalMedicine. 2022 Jul 16;51:101554. doi: 10.1016/j.eclinm.2022.101554. eCollection 2022 Sep.

Helpful Links

• NDA for Paragard (TCu380A)

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2017
• Primary Completion (Actual): June 6, 2022
• Study Completion (Actual): June 6, 2022

Study Registration Dates

• First Submitted: February 9, 2017
• First Submitted That Met QC Criteria: April 18, 2017
• First Posted (Actual): April 21, 2017

Study Record Updates

• Last Update Posted (Actual): September 25, 2024
• Last Update Submitted That Met QC Criteria: September 19, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Healthy Women; Female Contraception; IUD
• Other Study ID Numbers: CCN016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No