CompletedNCT03124160Updated Sep 25, 2024Results posted

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

A Phase 3 interventional study of Mona Lisa® NT Cu380 Mini and ParaGard® TCu380A in Healthy Women and Female Contraception, sponsored by FHI 360. Completed at 16 sites in United States. Open to female participants aged 16 Years to 40 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-09-25.

Sponsored by FHI 360 · Phase 3, Interventional, and Other

Phase: Phase 3
Study type: Interventional
Enrollment: 1,105
Allocation: Randomized
Ages: 16 Years to 40 Years
Sex: Female

Study summary

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.

Read the 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.

Conditions studied

Healthy Women
Female Contraception

Keywords

Healthy Women
Female Contraception
IUD

In context

Lead sponsor

FHI 360 is the lead sponsor of 56 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 16 Years to 40 Years
Sexes eligible: Female
Accepts healthy volunteers: Yes

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

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 design

Phase: Phase 3
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Single (Participant)
Enrollment: 1,105 participants (actual)

Study arms

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
Active comparator
ParaGard® TCu380A
ParaGard® TCU380A containing 380mm2 of copper surface inserted into the uterine cavity.
Drug: ParaGard® TCu380A

Interventions

DrugMona Lisa® NT Cu380 Mini
copper intrauterine device
Also known as: NT380-Mini, NTCu380-Mini
DrugParaGard® TCu380A
copper intrauterine device
Also known as: T380

What researchers measure

Primary outcomes

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
Time frame: 3 years

Secondary outcomes

IUD Continuation
IUD continuation at 36-months by product
Time frame: 3 years
Failed IUD Insertion
Failed IUD insertion as measured by inability to place the IUD correctly
Time frame: Immediate after IUD insertion attempt
Uterine Perforation
Uterine perforation as measured by ultrasound
Time frame: 3 years
IUD Expulsion (Complete and Partial)
When the IUD is expelled from the uterus, either completely or partially.
Time frame: 3 years
Vaginal Bleeding Patterns
Proportion of cycles with heavy bleeding (more than 4 sanitary products in a day)
Time frame: 1 year
Pelvic Pain as Measured in the Subject Diary
Percent of cycles with any pelvic pain will be calculated using all available cycles
Time frame: 1 year
Dysmenorrhea
Number of participants who experienced any dysmenorrhea during the trial
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 3 years

Results

Posted Sep 25, 2024

Participant flow

Participant flow — Overall Study
Milestone	Mona Lisa® NT Cu380 Mini	ParaGard® TCu380A
Started	887	218
Completed	426	91
Not completed	461	127

Outcome measures

PrimaryPregnancy 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

Time frame:: 3 years
Reported as:: Number · Pearl Index = Num preg per 100 person yr

Pregnancy Rate of Mona Lisa Copper IUD Over 3 Years
Pearl Index = Num preg per 100 person yr	Mona Lisa NT Cu380 Mini Participants <36 Years of Age
Pregnancy Rate of Mona Lisa Copper IUD Over 3 Years	1.86 (1.20 to 2.74)

SecondaryIUD Continuation

IUD continuation at 36-months by product

Time frame:: 3 years
Reported as:: Count of participants · Participants

IUD Continuation
Participants	Mona Lisa® NT Cu380 Mini	ParaGard® TCu380A
IUD Continuation	426	91

SecondaryFailed IUD Insertion

Failed IUD insertion as measured by inability to place the IUD correctly

Time frame:: Immediate after IUD insertion attempt
Reported as:: Number · participants

Failed IUD Insertion
participants	Mona Lisa® NT Cu380 Mini	ParaGard® TCu380A
Failed IUD Insertion	1	1

SecondaryUterine Perforation

Uterine perforation as measured by ultrasound

Time frame:: 3 years
Reported as:: Count of participants · Participants

Uterine Perforation
Participants	Mona Lisa® NT Cu380 Mini	ParaGard® TCu380A
Uterine Perforation	1	0

SecondaryIUD Expulsion (Complete and Partial)

When the IUD is expelled from the uterus, either completely or partially.

Time frame:: 3 years
Reported as:: Count of participants · Participants

IUD Expulsion (Complete and Partial)
Participants	Mona Lisa® NT Cu380 Mini	ParaGard® TCu380A
IUD Expulsion (Complete and Partial)	66	22

SecondaryVaginal Bleeding Patterns

Proportion of cycles with heavy bleeding (more than 4 sanitary products in a day)

Time frame:: 1 year
Reported as:: Mean · percent

Vaginal Bleeding Patterns
percent	Mona Lisa® NT Cu380 Mini	ParaGard® TCu380A
Vaginal Bleeding Patterns	54.4 (53.43 to 55.46)	55.7 (53.54 to 57.75)

SecondaryPelvic Pain as Measured in the Subject Diary

Percent of cycles with any pelvic pain will be calculated using all available cycles

Time frame:: 1 year
Reported as:: Number · percent

Pelvic Pain as Measured in the Subject Diary
percent	Mona Lisa® NT Cu380 Mini	ParaGard® TCu380A
Pelvic Pain as Measured in the Subject Diary	72.3 (71.3 to 73.2)	72.3 (70.4 to 74.1)

SecondaryDysmenorrhea

Number of participants who experienced any dysmenorrhea during the trial

Time frame:: 3 years
Reported as:: Count of participants · Participants

Dysmenorrhea
Participants	Mona Lisa® NT Cu380 Mini	ParaGard® TCu380A
Dysmenorrhea	396	100

SecondaryPain 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

Time frame:: Pain level 10 minutes after IUD insertion
Reported as:: Mean · units on a scale

Pain With and Shortly After Insertion as Recorded by Study Subjects
units on a scale	Mona Lisa® NT Cu380 Mini	ParaGard® TCu380A
Pain With and Shortly After Insertion as Recorded by Study Subjects	1.8 ± 1.92	2.1 ± 1.83

SecondaryEase of IUD Insertion as Recorded by the Investigator

Investigator to assess ease of IUD insertion (easy, somewhat easy, somewhat hard or hard)

Time frame:: Right after IUD insertion
Reported as:: Count of participants · Participants

Ease of IUD Insertion as Recorded by the Investigator
Participants	Mona Lisa® NT Cu380 Mini	ParaGard® TCu380A
Easy	694	161
Somewhat easy	132	43
Somewhat hard	41	6
Hard	8	3

SecondaryOverall Product Satisfaction as Measured by Acceptability Questions Asked of Subjects

Overall product satisfaction level at exit visit (highly satisfied, satisfied, dissatisfied, highly dissatisfied)

Time frame:: 3 years
Reported as:: Count of participants · Participants

Overall Product Satisfaction as Measured by Acceptability Questions Asked of Subjects
Participants	Mona Lisa® NT Cu380 Mini	ParaGard® TCu380A
Highly satisfied	364	92
Satisfied	248	49
Dissatisfied	118	43
Highly dissatisfied	31	10

Adverse events

Collected over 3 years. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Mona Lisa® NT Cu380 Mini	0/887 (0%)	32/887 (3.6%)	742/875 (84.8%)
ParaGard® TCu380A	0/218 (0%)	3/218 (1.4%)	183/213 (85.9%)

Most frequent serious events

Showing 10 of 32

Most frequent serious events
Event	Mona Lisa® NT Cu380 Mini	ParaGard® TCu380A
appendicitisInfections and infestations	8/887	0/218
limb injuryInjury, poisoning and procedural complications	0/887	1/218
ovarian massReproductive system and breast disorders	0/887	1/218
rashSkin and subcutaneous tissue disorders	0/887	1/218
pyelonephritisInfections and infestations	4/887	0/218
suicidal ideationPsychiatric disorders	2/887	0/218
suicidal attemptPsychiatric disorders	2/887	0/218
anaphylactic reactionImmune system disorders	2/887	0/218
infected biteInfections and infestations	1/887	0/218
tubo-ovarian abscessInfections and infestations	1/887	0/218

Most frequent other events

Most frequent other events
Event	Mona Lisa® NT Cu380 Mini	ParaGard® TCu380A
procedural painInjury, poisoning and procedural complications	511/875	135/213
dysmenorrhoeaReproductive system and breast disorders	390/875	100/213
menorrhagiaReproductive system and breast disorders	315/875	82/213
metrorrhagiaReproductive system and breast disorders	250/875	54/213
pelvic painReproductive system and breast disorders	186/875	46/213
uterine spasmReproductive system and breast disorders	71/875	22/213
abdominal painGastrointestinal disorders	61/875	16/213
dyspareuniaReproductive system and breast disorders	61/875	8/213
bacterial vaginosisInfections and infestations	48/875	11/213

Baseline characteristics

Females aged 17-40 interested in using a contraceptive method

Age, Continuous
Age, Continuous(years)	Mona Lisa® NT Cu380 Mini	ParaGard® TCu380A	Total
Mean	26.3 ± 5.23	26.3 ± 4.96	26.3 ± 5.19

Sex: Female, Male
Sex: Female, Male(Participants)	Mona Lisa® NT Cu380 Mini	ParaGard® TCu380A	Total
Female	887	218	1105
Male	0	0	0

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Mona Lisa® NT Cu380 Mini	ParaGard® TCu380A	Total
Hispanic or Latino	117	31	148
Not Hispanic or Latino	765	187	952
Unknown or Not Reported	5	0	5

Number of Participants
Number of Participants(Participants)	Mona Lisa® NT Cu380 Mini	ParaGard® TCu380A	Total
Count of participants	887	218	1105

Study locations

16 sites

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

References and documents

Publications

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. PubMed 516121 ↗
Sivin I, Tatum HJ. Four years of experience with the TCu 380A intrauterine contraceptive device. Fertil Steril. 1981 Aug;36(2):159-63. PubMed 7262334 ↗
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. PubMed 1797462 ↗
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. PubMed 2085966 ↗
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. PubMed 17531622 ↗
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. PubMed 26348177 ↗
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. PubMed 20664389 ↗
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. PubMed 12336868 ↗
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. PubMed 1844327 ↗
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. PubMed 12684147 ↗
Ott MA, Sucato GS; Committee on Adolescence. Contraception for adolescents. Pediatrics. 2014 Oct;134(4):e1257-81. doi: 10.1542/peds.2014-2300. PubMed 25266435 ↗
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. PubMed 22996129 ↗
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. PubMed 27467196 ↗
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. PubMed 25601352 ↗
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. PubMed 1347812 ↗
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. PubMed 35865736 ↗

Study documents

Study protocol · Dec 19, 2018
Statistical analysis plan · Oct 8, 2019
Informed consent form · Jan 3, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Sep 25, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03124160
Lead sponsor: FHI 360
Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Health Decisions
Responsible party: Sponsor
First posted: Apr 21, 2017
Start date: May 26, 2017
Primary completion: Jun 6, 2022
Completion: Jun 6, 2022
Results posted: Sep 25, 2024
Last update: Sep 25, 2024

Study contacts

Diana Blithe

study director · National Institute of Child Health & Human Development (NICHD)

David Hubacher

study director · FHI 360

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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