Mirena Extension Trial (MET)

Multi-center, Open-label, Uncontrolled Study to Assess Contraceptive Efficacy and Safety of Mirena During Extended Use Beyond 5 Years in Women 18 to 35 Years of Age Including a Subgroup Evaluation of Treatment Effect on Heavy Menstrual Bleeding

The study is performed to assess if Mirena is effective and safe as a birth control method beyond 5 years of use. Further the menstrual blood loss (in women that had Mirena inserted for the indication heavy menstrual bleeding [HMB]) and safety will be assessed.

Study Overview

• Status: Completed
• Conditions: Contraception
• Intervention / Treatment: Drug: Levonorgestrel IUS (Mirena, BAY86-5028)

• Study Type: Interventional
• Enrollment (Actual): 364
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36608-6703
  • Arizona
    • Phoenix, Arizona, United States, 85032
    • Scottsdale, Arizona, United States, 85251
    • Tucson, Arizona, United States, 85712
  • California
    • Encinitas, California, United States, 92024
    • San Francisco, California, United States, 94110
    • Ventura, California, United States, 93003
  • Colorado
    • Aurora, Colorado, United States, 80045
  • Georgia
    • Atlanta, Georgia, United States, 30342
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
  • Indiana
    • Fort Wayne, Indiana, United States, 46825
    • Newburgh, Indiana, United States, 47630-8940
  • Maryland
    • Frederick, Maryland, United States, 21702
    • Pikesville, Maryland, United States, 21208
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
  • Michigan
    • Saginaw, Michigan, United States, 48604
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
  • Nevada
    • Las Vegas, Nevada, United States, 89106
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756-1000
  • New Jersey
    • Lawrenceville, New Jersey, United States, 08648
    • Neptune, New Jersey, United States, 07753
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
  • New York
    • New York, New York, United States, 10032
    • Port Jefferson, New York, United States, 11777
  • North Carolina
    • Asheville, North Carolina, United States, 28801
    • Durham, North Carolina, United States, 27713
    • Greensboro, North Carolina, United States, 27408
    • Hickory, North Carolina, United States, 28602
    • Morehead City, North Carolina, United States, 28557
    • New Bern, North Carolina, United States, 28562
    • Winston-Salem, North Carolina, United States, 27103-1749
  • Ohio
    • Franklin, Ohio, United States, 45005-2593
    • Mayfield Heights, Ohio, United States, 44124
  • Oregon
    • Portland, Oregon, United States, 97239
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16507
    • Philadelphia, Pennsylvania, United States, 19104
    • Philadelphia, Pennsylvania, United States, 19107
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
  • Texas
    • Austin, Texas, United States, 78758
    • Fort Worth, Texas, United States, 76104-4145
    • Houston, Texas, United States, 77030
  • Utah
    • Draper, Utah, United States, 84020-7163
  • Virginia
    • Midlothian, Virginia, United States, 23114
    • North Chesterfield, Virginia, United States, 23235
    • Roanoke, Virginia, United States, 24013-2256
    • Virginia Beach, Virginia, United States, 23456
  • Washington
    • Seattle, Washington, United States, 98105
    • Seattle, Washington, United States, 98122
    • Spokane, Washington, United States, 99207-1240

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Signed and dated informed consent
• Women, 18 to 35 years of age at the time of screening (visit 1) who are currently using Mirena for contraception or for contraception and heavy menstrual bleeding. The duration of use of the current Mirena has to be at least 4 years 6 months at the start of screening phase but not more than 5 years at visit 2 and the woman is willing to continue with its use and has a continuing need for contraception.
• Normal or clinically insignificant cervical smear not requiring further follow up

Exclusion Criteria:

• Menopausal symptoms with Follicle-stimulating hormone>30 mIU/ml
• Pregnancy or suspicion of pregnancy
• Uterine bleeding of unknown etiology
• Untreated acute cervicitis or vaginitis or other lower genital tract infections
• Increased susceptibility to pelvic infection
• Acute pelvic inflammatory disease (PID) or a history of PID unless successfully treated and which, in the investigator's opinion, has not negatively affected subject's fertility
• Congenital or acquired uterine anomaly if it distorts the uterine cavity
• History of, diagnosed or suspected genital or other malignancy and untreated cervical dysplasia
• Any active acute liver disease or liver tumor (benign or malignant)
• Clinically significant endometrial polyp(s)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Levonorgestrel IUS (Mirena, BAY86-5028); Mirena during extended use (Years 6 to 8).	Drug: Levonorgestrel IUS (Mirena, BAY86-5028); Levonorgestrel (LNG) intrauterine delivery system (IUS) with an initial in vitro release rate of 20 μg levonorgestrel per day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Pregnancies Per 100 Women Years (Pearl Index [PI]) Within Years 6 Thru 8 of Mirena Use	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.	Years 6 to 8 of Mirena use

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Menstrual Blood Loss (MBL) During a 30-day Period Starting at the Baseline Visit and at the End of Years 6, 7 and 8	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).	Baseline and end of Years 6, 7 and 8 of Mirena use
Number of Participants With Menstrual Blood Loss (MBL) (>= 80 ml Per 30 Days) at End of Year 6, 7 and 8 of Mirena Use	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.	At end of Year 6, 7 and 8 of Mirena use
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	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.	Years 6 to 8 of Mirena use

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total LNG Concentrations in Plasma Estimated Based on the Final 8-year Population Pharmacokinetics (popPK) Model	A population pharmacokinetic (popPK) analysis was performed including sparse data from the study.	At the beginning of Year 6 (baseline) and at the end of Years 6, 7, and 8 of Mirena use
Participant's Satisfaction With Mirena by Visit	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.	Baseline, at end of Year 6, 7 and 8 of Mirena use

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find results for studies related to Bayer Healthcare products.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 22, 2016
• Primary Completion (ACTUAL): May 28, 2021
• Study Completion (ACTUAL): May 28, 2021

Study Registration Dates

• First Submitted: December 5, 2016
• First Submitted That Met QC Criteria: December 5, 2016
• First Posted (ESTIMATE): December 7, 2016

Study Record Updates

• Last Update Posted (ACTUAL): April 28, 2022
• Last Update Submitted That Met QC Criteria: April 25, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Heavy menstrual bleeding; Birth Control
• Additional Relevant MeSH Terms: Pathologic Processes; Uterine Diseases; Hemorrhage; Menstruation Disturbances; Uterine Hemorrhage; Menorrhagia; Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Levonorgestrel
• Other Study ID Numbers: 18649

Drug and device information, study documents

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