Female Contraception, Healthy Women
Conditions
Keywords
Healthy Women, Female Contraception, IUD
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.
Interventions
DRUGMona Lisa® NT Cu380 Mini
copper intrauterine device
DRUGParaGard® TCu380A
copper intrauterine device
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Premier Research
FHI 360
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
FEMALE
Age
16 Years to 40 Years
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pregnancy Rate of Mona Lisa Copper IUD Over 3 Years | 3 years | Pearl Index is a measure of contraceptive efficacy used by the FDA that summarizes number of method failures per 100 person years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Failed IUD Insertion | Immediate after IUD insertion attempt | Failed IUD insertion as measured by inability to place the IUD correctly |
| Uterine Perforation | 3 years | Uterine perforation as measured by ultrasound |
| IUD Expulsion (Complete and Partial) | 3 years | When the IUD is expelled from the uterus, either completely or partially. |
| Vaginal Bleeding Patterns | 1 year | Proportion of cycles with heavy bleeding (more than 4 sanitary products in a day) |
| IUD Continuation | 3 years | IUD continuation at 36-months by product |
| Dysmenorrhea | 3 years | Number of participants who experienced any dysmenorrhea during the trial |
| Pain With and Shortly After Insertion as Recorded by Study Subjects | Pain level 10 minutes after IUD insertion | 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 |
| Ease of IUD Insertion as Recorded by the Investigator | Right after IUD insertion | Investigator to assess ease of IUD insertion (easy, somewhat easy, somewhat hard or hard) |
| Overall Product Satisfaction as Measured by Acceptability Questions Asked of Subjects | 3 years | Overall product satisfaction level at exit visit (highly satisfied, satisfied, dissatisfied, highly dissatisfied) |
| Pelvic Pain as Measured in the Subject Diary | 1 year | Percent of cycles with any pelvic pain will be calculated using all available cycles |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mona Lisa® NT Cu380 Mini Mona Lisa® NT Cu380 Mini containing 380mm2 of copper surface inserted into the uterine cavity.
Mona Lisa® NT Cu380 Mini: Mona Lisa® NT Cu380 Mini | 887 |
| ParaGard® TCu380A ParaGard® TCU380A containing 380mm2 of copper surface inserted into the uterine cavity.
ParaGard® TCu380A: ParaGard® TCu380A | 218 |
| Total | 1,105 |
Baseline characteristics
| Characteristic | Mona Lisa® NT Cu380 Mini | ParaGard® TCu380A | Total |
|---|---|---|---|
| Age, Continuous | 26.3 years STANDARD_DEVIATION 5.23 | 26.3 years STANDARD_DEVIATION 4.96 | 26.3 years STANDARD_DEVIATION 5.19 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 117 Participants | 31 Participants | 148 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 765 Participants | 187 Participants | 952 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 0 Participants | 5 Participants |
| Number of Participants | 887 Participants | 218 Participants | 1105 Participants |
| Sex: Female, Male Female | 887 Participants | 218 Participants | 1105 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 887 | 0 / 218 |
| other Total, other adverse events | 742 / 875 | 183 / 213 |
| serious Total, serious adverse events | 32 / 887 | 3 / 218 |
Outcome results
Primary
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
Population: includes only participants with an evaluable cycle for estimating efficacy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mona Lisa NT Cu380 Mini Participants <36 Years of Age | Pregnancy Rate of Mona Lisa Copper IUD Over 3 Years | 1.86 Pearl Index = Num preg per 100 person yr |
Secondary
Dysmenorrhea
Number of participants who experienced any dysmenorrhea during the trial
Time frame: 3 years
Population: User population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mona Lisa NT Cu380 Mini Participants <36 Years of Age | Dysmenorrhea | 396 Participants |
| ParaGard® TCu380A | Dysmenorrhea | 100 Participants |
Secondary
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
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mona Lisa NT Cu380 Mini Participants <36 Years of Age | Ease of IUD Insertion as Recorded by the Investigator | Easy | 694 Participants |
| Mona Lisa NT Cu380 Mini Participants <36 Years of Age | Ease of IUD Insertion as Recorded by the Investigator | Somewhat easy | 132 Participants |
| Mona Lisa NT Cu380 Mini Participants <36 Years of Age | Ease of IUD Insertion as Recorded by the Investigator | Somewhat hard | 41 Participants |
| Mona Lisa NT Cu380 Mini Participants <36 Years of Age | Ease of IUD Insertion as Recorded by the Investigator | Hard | 8 Participants |
| ParaGard® TCu380A | Ease of IUD Insertion as Recorded by the Investigator | Hard | 3 Participants |
| ParaGard® TCu380A | Ease of IUD Insertion as Recorded by the Investigator | Easy | 161 Participants |
| ParaGard® TCu380A | Ease of IUD Insertion as Recorded by the Investigator | Somewhat hard | 6 Participants |
| ParaGard® TCu380A | Ease of IUD Insertion as Recorded by the Investigator | Somewhat easy | 43 Participants |
Secondary
Failed IUD Insertion
Failed IUD insertion as measured by inability to place the IUD correctly
Time frame: Immediate after IUD insertion attempt
Population: Treated population: uterus was successfully sounded and IUD insertion attempt was made
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mona Lisa NT Cu380 Mini Participants <36 Years of Age | Failed IUD Insertion | 1 participants |
| ParaGard® TCu380A | Failed IUD Insertion | 1 participants |
Secondary
IUD Continuation
IUD continuation at 36-months by product
Time frame: 3 years
Population: Participants with successful IUD insertion
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mona Lisa NT Cu380 Mini Participants <36 Years of Age | IUD Continuation | 426 Participants |
| ParaGard® TCu380A | IUD Continuation | 91 Participants |
Secondary
IUD Expulsion (Complete and Partial)
When the IUD is expelled from the uterus, either completely or partially.
Time frame: 3 years
Population: user population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mona Lisa NT Cu380 Mini Participants <36 Years of Age | IUD Expulsion (Complete and Partial) | 66 Participants |
| ParaGard® TCu380A | IUD Expulsion (Complete and Partial) | 22 Participants |
Secondary
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
Population: User population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mona Lisa NT Cu380 Mini Participants <36 Years of Age | Overall Product Satisfaction as Measured by Acceptability Questions Asked of Subjects | Highly satisfied | 364 Participants |
| Mona Lisa NT Cu380 Mini Participants <36 Years of Age | Overall Product Satisfaction as Measured by Acceptability Questions Asked of Subjects | Satisfied | 248 Participants |
| Mona Lisa NT Cu380 Mini Participants <36 Years of Age | Overall Product Satisfaction as Measured by Acceptability Questions Asked of Subjects | Dissatisfied | 118 Participants |
| Mona Lisa NT Cu380 Mini Participants <36 Years of Age | Overall Product Satisfaction as Measured by Acceptability Questions Asked of Subjects | Highly dissatisfied | 31 Participants |
| ParaGard® TCu380A | Overall Product Satisfaction as Measured by Acceptability Questions Asked of Subjects | Highly dissatisfied | 10 Participants |
| ParaGard® TCu380A | Overall Product Satisfaction as Measured by Acceptability Questions Asked of Subjects | Highly satisfied | 92 Participants |
| ParaGard® TCu380A | Overall Product Satisfaction as Measured by Acceptability Questions Asked of Subjects | Dissatisfied | 43 Participants |
| ParaGard® TCu380A | Overall Product Satisfaction as Measured by Acceptability Questions Asked of Subjects | Satisfied | 49 Participants |
Secondary
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
Population: User population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mona Lisa NT Cu380 Mini Participants <36 Years of Age | Pain With and Shortly After Insertion as Recorded by Study Subjects | 1.8 units on a scale | Standard Deviation 1.92 |
| ParaGard® TCu380A | Pain With and Shortly After Insertion as Recorded by Study Subjects | 2.1 units on a scale | Standard Deviation 1.83 |
Secondary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mona Lisa NT Cu380 Mini Participants <36 Years of Age | Pelvic Pain as Measured in the Subject Diary | 72.3 percent |
| ParaGard® TCu380A | Pelvic Pain as Measured in the Subject Diary | 72.3 percent |
Secondary
Uterine Perforation
Uterine perforation as measured by ultrasound
Time frame: 3 years
Population: User population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mona Lisa NT Cu380 Mini Participants <36 Years of Age | Uterine Perforation | 1 Participants |
| ParaGard® TCu380A | Uterine Perforation | 0 Participants |
Secondary
Vaginal Bleeding Patterns
Proportion of cycles with heavy bleeding (more than 4 sanitary products in a day)
Time frame: 1 year
Population: User population with evaluable cycles
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Mona Lisa NT Cu380 Mini Participants <36 Years of Age | Vaginal Bleeding Patterns | 54.4 percent |
| ParaGard® TCu380A | Vaginal Bleeding Patterns | 55.7 percent |