Clinical trial NCT03124160: Compare Two Copper IUDs: Mona Lisa NT Cu380 Mini and ParaGard
Official title: A Multi-center, Single-blind, Randomized Clinical Trial to Compare Two Copper IUDs: Mona Lisa NT Cu380 Mini and ParaGard
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Healthy Women
Female Contraception
Keywords: Healthy Women
Female Contraception
IUD
Lead sponsor: FHI 360
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Health Decisions
First posted: 2017-04-21
Enrollment: 1105
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Pregnancy Rate of Mona Lisa Copper IUD Over 3 Years
timeFrame: 3 years
Secondary outcomes:
measure: IUD Continuation
timeFrame: 3 years
measure: Failed IUD Insertion
timeFrame: Immediate after IUD insertion attempt
measure: Uterine Perforation
timeFrame: 3 years
measure: IUD Expulsion (Complete and Partial)
timeFrame: 3 years
measure: Vaginal Bleeding Patterns
timeFrame: 1 year
measure: Pelvic Pain as Measured in the Subject Diary
timeFrame: 1 year
measure: Dysmenorrhea
timeFrame: 3 years
measure: Pain With and Shortly After Insertion as Recorded by Study Subjects
timeFrame: Pain level 10 minutes after IUD insertion
measure: Ease of IUD Insertion as Recorded by the Investigator
timeFrame: Right after IUD insertion
measure: Overall Product Satisfaction as Measured by Acceptability Questions Asked of Subjects
timeFrame: 3 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Essential Access Health
state: California
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Denver
country: United States
facility: University of Colorado
state: Colorado
city: Honolulu
country: United States
facility: University of Hawaii
state: Hawaii
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Boston Medical Center Corporation
state: Massachusetts
city: Boston
country: United States
facility: Planned Parenthood League of Massachusetts
state: Massachusetts
city: New York
country: United States
facility: Planned Parenthood of New York
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Norfolk
country: United States
facility: Eastern Virginia Medical School
state: Virginia
Study officials:
affiliation: National Institute of Child Health & Human Development (NICHD)
name: Diana Blithe
role: STUDY_DIRECTOR
affiliation: FHI 360
name: David Hubacher
role: STUDY_DIRECTOR
References:
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citation: 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.
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citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.