Trial Outcomes & Findings for Mirena Extension Trial (NCT NCT02985541)
NCT ID: NCT02985541
Last Updated: 2022-04-28
Results Overview
The Pearl Index (PI) is defined as the number of pregnancies per 100 women years. The 3-year PI (Years 6 to 8) was obtained by dividing the number of pregnancies the occurred during that time (starting at Day 1 Year 6 and up to Day 365 of Year 8) by the time (in 100 women years) that the women were at risk of getting pregnant during that time.
COMPLETED
PHASE3
364 participants
Years 6 to 8 of Mirena use
2022-04-28
Participant Flow
A total of 364 women entered treatment period. Of these, 2 women were not valid for FAS (full analysis set)/SAF (safety analysis set)/PAS(primary analysis set) due to incomplete source data verification.
Participant milestones
| Measure |
Levonorgestrel IUS (Mirena, BAY86-5028)
Mirena during extended use (Years 6 to 8).
|
|---|---|
|
Overall Study
STARTED
|
364
|
|
Overall Study
Valid for FAS
|
362
|
|
Overall Study
Continued Into Year 7 of Mirena Use
|
305
|
|
Overall Study
Continued Into Year 8 of Mirena Use
|
243
|
|
Overall Study
COMPLETED
|
223
|
|
Overall Study
NOT COMPLETED
|
141
|
Reasons for withdrawal
| Measure |
Levonorgestrel IUS (Mirena, BAY86-5028)
Mirena during extended use (Years 6 to 8).
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
33
|
|
Overall Study
Lost to Follow-up
|
26
|
|
Overall Study
Adverse Event
|
27
|
|
Overall Study
Physician Decision
|
2
|
|
Overall Study
Pregnancy
|
2
|
|
Overall Study
Wish for pregnancy
|
44
|
|
Overall Study
Other reason
|
5
|
|
Overall Study
Not valid for analysis
|
2
|
Baseline Characteristics
Mirena Extension Trial
Baseline characteristics by cohort
| Measure |
Levonorgestrel IUS (Mirena, BAY86-5028)
n=362 Participants
Mirena during extended use (Years 6 to 8).
|
|---|---|
|
Age, Continuous
|
29.4 years
STANDARD_DEVIATION 3.1 • n=39 Participants
|
|
Sex: Female, Male
Female
|
362 Participants
n=39 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=39 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
41 Participants
n=39 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
319 Participants
n=39 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=39 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=39 Participants
|
|
Race (NIH/OMB)
Asian
|
9 Participants
n=39 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=39 Participants
|
|
Race (NIH/OMB)
Black or African American
|
51 Participants
n=39 Participants
|
|
Race (NIH/OMB)
White
|
273 Participants
n=39 Participants
|
|
Race (NIH/OMB)
More than one race
|
14 Participants
n=39 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
13 Participants
n=39 Participants
|
|
Parity
Nulliparous
|
171 Participants
n=39 Participants
|
|
Parity
Parous
|
191 Participants
n=39 Participants
|
PRIMARY outcome
Timeframe: Years 6 to 8 of Mirena usePopulation: All women in the full analysis set (FAS) with an age of 33 years or younger at baseline visit (i.e. an age of 36 or younger at end of year 8).
The Pearl Index (PI) is defined as the number of pregnancies per 100 women years. The 3-year PI (Years 6 to 8) was obtained by dividing the number of pregnancies the occurred during that time (starting at Day 1 Year 6 and up to Day 365 of Year 8) by the time (in 100 women years) that the women were at risk of getting pregnant during that time.
Outcome measures
| Measure |
Levonorgestrel IUS (Mirena, BAY86-5028)
n=346 Participants
Mirena during extended use (Years 6 to 8).
|
|---|---|
|
Number of Pregnancies Per 100 Women Years (Pearl Index [PI]) Within Years 6 Thru 8 of Mirena Use
|
0.28 Pregnancies per 100 women years
Interval 0.03 to 1.0
|
SECONDARY outcome
Timeframe: Baseline and end of Years 6, 7 and 8 of Mirena usePopulation: Women who had Mirena inserted for HMB
Menstrual blood loss (MBL) during a 30-day period starting at the baseline visit and at the end of Year 6, Year 7, and Year 8, measured by the alkaline hematin method. The assessment of this variable was restricted to women who had Mirena inserted for heavy menstrual bleeding (HMB).
Outcome measures
| Measure |
Levonorgestrel IUS (Mirena, BAY86-5028)
n=6 Participants
Mirena during extended use (Years 6 to 8).
|
|---|---|
|
Menstrual Blood Loss (MBL) During a 30-day Period Starting at the Baseline Visit and at the End of Years 6, 7 and 8
End of Year 8
|
0.000 mL/30 days
Interval 0.0 to 0.0
|
|
Menstrual Blood Loss (MBL) During a 30-day Period Starting at the Baseline Visit and at the End of Years 6, 7 and 8
Beginning of Year 6 (baseline)
|
0.000 mL/30 days
Interval 0.0 to 2.32
|
|
Menstrual Blood Loss (MBL) During a 30-day Period Starting at the Baseline Visit and at the End of Years 6, 7 and 8
End of Year 6
|
0.000 mL/30 days
Interval 0.0 to 0.0
|
|
Menstrual Blood Loss (MBL) During a 30-day Period Starting at the Baseline Visit and at the End of Years 6, 7 and 8
End of Year 7
|
0.000 mL/30 days
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: At end of Year 6, 7 and 8 of Mirena usePopulation: Women who had Mirena inserted for HMB
Categorized menstrual blood loss (MBL) (≥ 80 mL per 30 days) at end of Year 6, Year 7, and Year 8. The assessment of this variable was restricted to women who had Mirena inserted for HMB.
Outcome measures
| Measure |
Levonorgestrel IUS (Mirena, BAY86-5028)
n=6 Participants
Mirena during extended use (Years 6 to 8).
|
|---|---|
|
Number of Participants With Menstrual Blood Loss (MBL) (>= 80 ml Per 30 Days) at End of Year 6, 7 and 8 of Mirena Use
End of Year 8
|
0 Participants
|
|
Number of Participants With Menstrual Blood Loss (MBL) (>= 80 ml Per 30 Days) at End of Year 6, 7 and 8 of Mirena Use
End of Year 6
|
0 Participants
|
|
Number of Participants With Menstrual Blood Loss (MBL) (>= 80 ml Per 30 Days) at End of Year 6, 7 and 8 of Mirena Use
End of Year 7
|
0 Participants
|
SECONDARY outcome
Timeframe: Years 6 to 8 of Mirena usePopulation: Safety analysis set (SAF): All women who completed the baseline visit of the study, analyzed for the FAS.
Adverse event (AE) was defined as any untoward medical occurrence (ie any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a patient or clinical investigation subject after providing written informed consent for participation in the study. Serious adverse event (SAE) was defined as any untoward medical occurrence that, at any dose 1) resulted in death, 2) was life-threatening, 3) required inpatient hospitalization or prolongation of existing hospitalization, 4) resulted in persistent or significant disability/incapacity, 5) was a congenital anomaly/birth defect, or 6) was another medically important serious event as judged by the investigator. Treatment-emergent adverse event (TEAE) was defined as an AE that occurred on Day 1 Year 6 of Mirena use or later.
Outcome measures
| Measure |
Levonorgestrel IUS (Mirena, BAY86-5028)
n=362 Participants
Mirena during extended use (Years 6 to 8).
|
|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Any AE
|
249 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Any SAE
|
14 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: At the beginning of Year 6 (baseline) and at the end of Years 6, 7, and 8 of Mirena usePopulation: Concentrations were estimated for women who had Mirena still in place.
A population pharmacokinetic (popPK) analysis was performed including sparse data from the study.
Outcome measures
| Measure |
Levonorgestrel IUS (Mirena, BAY86-5028)
n=361 Participants
Mirena during extended use (Years 6 to 8).
|
|---|---|
|
Total LNG Concentrations in Plasma Estimated Based on the Final 8-year Population Pharmacokinetics (popPK) Model
At the beginning of Year 6 (baseline)
|
123 ng/L
Geometric Coefficient of Variation 38.3
|
|
Total LNG Concentrations in Plasma Estimated Based on the Final 8-year Population Pharmacokinetics (popPK) Model
At the end of Year 6
|
114 ng/L
Geometric Coefficient of Variation 38.7
|
|
Total LNG Concentrations in Plasma Estimated Based on the Final 8-year Population Pharmacokinetics (popPK) Model
At the end of Year 7
|
106 ng/L
Geometric Coefficient of Variation 39.2
|
|
Total LNG Concentrations in Plasma Estimated Based on the Final 8-year Population Pharmacokinetics (popPK) Model
At the end of Year 8
|
100 ng/L
Geometric Coefficient of Variation 39.9
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, at end of Year 6, 7 and 8 of Mirena usePopulation: Full analysis set (FAS): All women who completed the baseline visit of the study.
Participants were asked to evaluate their satisfaction with Mirena on a 5-point scale as very satisfied, somewhat satisfied, neither satisfied or dissatisfied, dissatisfied or very dissatisfied.
Outcome measures
| Measure |
Levonorgestrel IUS (Mirena, BAY86-5028)
n=362 Participants
Mirena during extended use (Years 6 to 8).
|
|---|---|
|
Participant's Satisfaction With Mirena by Visit
Baseline (very satisfied)
|
342 Participants
|
|
Participant's Satisfaction With Mirena by Visit
Baseline (somewhat satisfied)
|
20 Participants
|
|
Participant's Satisfaction With Mirena by Visit
Baseline (neither satisfied nor dissatisfied)
|
0 Participants
|
|
Participant's Satisfaction With Mirena by Visit
Baseline (dissatisfied)
|
0 Participants
|
|
Participant's Satisfaction With Mirena by Visit
Baseline (very dissatisfied)
|
0 Participants
|
|
Participant's Satisfaction With Mirena by Visit
Year 6 (very satisfied)
|
279 Participants
|
|
Participant's Satisfaction With Mirena by Visit
Year 6 (somewhat satisfied)
|
20 Participants
|
|
Participant's Satisfaction With Mirena by Visit
Year 6 (neither satisfied nor dissatisfied)
|
3 Participants
|
|
Participant's Satisfaction With Mirena by Visit
Year 6 (dissatisfied)
|
0 Participants
|
|
Participant's Satisfaction With Mirena by Visit
Year 6 (very dissatisfied)
|
0 Participants
|
|
Participant's Satisfaction With Mirena by Visit
Year 7 (very satisfied)
|
218 Participants
|
|
Participant's Satisfaction With Mirena by Visit
Year 7 (somewhat satisfied)
|
20 Participants
|
|
Participant's Satisfaction With Mirena by Visit
Year 7 (neither satisfied nor dissatisfied)
|
1 Participants
|
|
Participant's Satisfaction With Mirena by Visit
Year 7 (dissatisfied)
|
3 Participants
|
|
Participant's Satisfaction With Mirena by Visit
Year 7 (very dissatisfied)
|
1 Participants
|
|
Participant's Satisfaction With Mirena by Visit
Year 8 (very satisfied)
|
207 Participants
|
|
Participant's Satisfaction With Mirena by Visit
Year 8 (somewhat satisfied)
|
13 Participants
|
|
Participant's Satisfaction With Mirena by Visit
Year 8 (neither satisfied nor dissatisfied)
|
3 Participants
|
|
Participant's Satisfaction With Mirena by Visit
Year 8 (dissatisfied)
|
0 Participants
|
|
Participant's Satisfaction With Mirena by Visit
Year 8 (very dissatisfied)
|
0 Participants
|
Adverse Events
Levonorgestrel IUS (Mirena, BAY86-5028)
Serious adverse events
| Measure |
Levonorgestrel IUS (Mirena, BAY86-5028)
n=362 participants at risk
Mirena during extended use (Years 6 to 8).
|
|---|---|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
0.28%
1/362 • Number of events 1 • Years 6 to 8 of Mirena use
|
|
Gastrointestinal disorders
Volvulus
|
0.28%
1/362 • Number of events 1 • Years 6 to 8 of Mirena use
|
|
Infections and infestations
Tooth abscess
|
0.28%
1/362 • Number of events 1 • Years 6 to 8 of Mirena use
|
|
Infections and infestations
Urinary tract infection
|
0.28%
1/362 • Number of events 1 • Years 6 to 8 of Mirena use
|
|
Injury, poisoning and procedural complications
Uterine perforation
|
0.83%
3/362 • Number of events 3 • Years 6 to 8 of Mirena use
|
|
Metabolism and nutrition disorders
Obesity
|
0.28%
1/362 • Number of events 1 • Years 6 to 8 of Mirena use
|
|
Nervous system disorders
Radial nerve palsy
|
0.28%
1/362 • Number of events 1 • Years 6 to 8 of Mirena use
|
|
Nervous system disorders
Vertebral artery dissection
|
0.28%
1/362 • Number of events 1 • Years 6 to 8 of Mirena use
|
|
Nervous system disorders
Cerebellar stroke
|
0.28%
1/362 • Number of events 1 • Years 6 to 8 of Mirena use
|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
|
0.28%
1/362 • Number of events 1 • Years 6 to 8 of Mirena use
|
|
Pregnancy, puerperium and perinatal conditions
Ectopic pregnancy with contraceptive device
|
0.28%
1/362 • Number of events 1 • Years 6 to 8 of Mirena use
|
|
Psychiatric disorders
Conversion disorder
|
0.28%
1/362 • Number of events 1 • Years 6 to 8 of Mirena use
|
|
Psychiatric disorders
Suicidal ideation
|
0.55%
2/362 • Number of events 2 • Years 6 to 8 of Mirena use
|
|
Psychiatric disorders
Bipolar disorder
|
0.28%
1/362 • Number of events 1 • Years 6 to 8 of Mirena use
|
|
Product Issues
Embedded device
|
0.28%
1/362 • Number of events 1 • Years 6 to 8 of Mirena use
|
Other adverse events
| Measure |
Levonorgestrel IUS (Mirena, BAY86-5028)
n=362 participants at risk
Mirena during extended use (Years 6 to 8).
|
|---|---|
|
Infections and infestations
Bacterial vaginosis
|
7.5%
27/362 • Number of events 40 • Years 6 to 8 of Mirena use
|
|
Infections and infestations
Nasopharyngitis
|
5.8%
21/362 • Number of events 29 • Years 6 to 8 of Mirena use
|
|
Infections and infestations
Urinary tract infection
|
7.5%
27/362 • Number of events 35 • Years 6 to 8 of Mirena use
|
|
Investigations
Weight increased
|
9.1%
33/362 • Number of events 33 • Years 6 to 8 of Mirena use
|
|
Psychiatric disorders
Anxiety
|
5.5%
20/362 • Number of events 22 • Years 6 to 8 of Mirena use
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60