Management of Initial Bleeding/Spotting Associated With the Levonorgestrel-releasing Intrauterine System (MIRENA)

• ClinicalTrials.gov Identifier: NCT01295294
• Recruitment Status: Completed
• First Posted: February 14, 2011
• Last Update Posted: November 4, 2014
• Sponsor: Bayer
• Information provided by (Responsible Party): Bayer

Tracking Information

• First Submitted Date: February 11, 2011
• First Posted Date: February 14, 2011
• Last Update Posted Date: November 4, 2014
• Study Start Date: March 2011
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 11, 2011): The primary efficacy variable will be the cumulative number of bleeding / spotting days [ Time Frame: During 90 day double-blind treatment period ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 8, 2013)

• To describe and compare the bleeding patterns observed in women during treatment period [ Time Frame: 90 day treatment period ]
• To describe and compare the bleeding patterns observed in women during follow-up period [ Time Frame: During the 30 day follow-up period ]
• Satisfaction with oral blinded study drug treatment for bleeding / spotting [ Time Frame: 90 day treatment period ]
• Occurrence of dysmenorrhea [ Time Frame: During 120 day study period ]
• Continuation rate with study drug [ Time Frame: During the 90 day treatment period ]
• Continuation rate with Mirena [ Time Frame: During 120 day study period ]
• Adverse Events Collection [ Time Frame: Until day 120 ]
• Number of spotting-only days [ Time Frame: During the 90-day treatment period ]
• Number of bleeding / spotting episodes [ Time Frame: During the 90-day treatment period ]
• Length of bleeding / spotting episodes [ Time Frame: During the 90-day treatment period ]
• Number of bleeding days with heavy intensity [ Time Frame: During the 90-day treatment period ]
• Change in the number of B/S days between Day 60 and Day 90 of MIRENA use and the 30-day follow-up period [ Time Frame: Up to day 120 ]
• Satisfaction with levonorgestrel-releasing intrauterine system [ Time Frame: Up to day 120 ]
• Number of days of pain medication for dysmenorrhea during the 90 day treatment period [ Time Frame: During the 90-day treatment period ]
• Number of bleeding-only days [ Time Frame: During the 90-day treatment period ]

Original Secondary Outcome Measures (submitted: February 11, 2011)

• To describe and compare the bleeding patterns observed in women during treatment period [ Time Frame: 90 day treatment period ]
• To describe and compare the bleeding patterns observed in women during follow-up period [ Time Frame: During the 30 day follow-up period ]
• Satisfaction with oral blinded study drug treatment for bleeding / spotting [ Time Frame: 90 day treatment period ]
• Occurrence of dysmenorrhea [ Time Frame: During 120 day study period ]
• Continuation rate with study drug [ Time Frame: During the 90 day treatment period ]
• Continuation rate with Mirena [ Time Frame: During 120 day study period ]
• Adverse Events Collection [ Time Frame: Until day 120 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Management of Initial Bleeding/Spotting Associated With the Levonorgestrel-releasing Intrauterine System (MIRENA)
• Official Title: International, Prospective, Double-blind, 3-arm Comparative, Randomized, Placebo-controlled Phase IV Study on the Effect of Counseling and Either Tranexamic Acid or Mefenamic Acid or Placebo, on the Management of Bleeding/Spotting in Women Using the Levonorgestrel-releasing Intrauterine System (MIRENA) for Contraception.
• Brief Summary: The purpose of the study is to investigate if the study drugs (tranexamic acid or mefenamic acid) can control irregular bleeding during the first 3 months of using Mirena. The study drugs tested are tested against placebo ("dummy medication not containing any active drug"). Treatment period is followed by a one-month period when study drugs are not taken but Mirena use is continued.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Uterine Hemorrhage

Intervention

• Drug: Tranexamic acid
  500 mg 3 times daily per oral during bleeding/spotting episodes
• Drug: Mefenamic acid
  500 mg 3 times daily per oral during bleeding/spotting episodes
• Drug: Placebo
  3 times daily per oral during bleeding/spotting episodes
• Drug: Mirena (Levonorgestrel IUS, BAY86-5028)
  In vitro release rate 20 microgram/24 hours. Intrauterine system

Study Arms

• Experimental: tranexamic acid + Mirena (Levonorgestrel IUS, BAY86-5028)
  Subjects with successful MIRENA insertion will receive treatments with tranexamic acid
  Interventions:

  • Drug: Tranexamic acid
  • Drug: Mirena (Levonorgestrel IUS, BAY86-5028)
• Experimental: mefenamic acid + Mirena (Levonorgestrel IUS, BAY86-5028)
  Subjects with successful MIRENA insertion will receive treatments with mefenamic acid
  Interventions:

  • Drug: Mefenamic acid
  • Drug: Mirena (Levonorgestrel IUS, BAY86-5028)
• Placebo Comparator: placebo + Mirena (Levonorgestrel IUS, BAY86-5028)
  Subjects with successful MIRENA insertion will receive placebo
  Interventions:

  • Drug: Placebo
  • Drug: Mirena (Levonorgestrel IUS, BAY86-5028)

• Publications *: Sørdal T, Inki P, Draeby J, O'Flynn M, Schmelter T. Management of initial bleeding or spotting after levonorgestrel-releasing intrauterine system placement: a randomized controlled trial. Obstet Gynecol. 2013 May;121(5):934-941. doi: 10.1097/AOG.0b013e31828c65d8.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 8, 2013): 187
• Original Estimated Enrollment (submitted: February 11, 2011): 186
• Actual Study Completion Date: December 2011
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Signed and dated informed consent
• Healthy female subjects requesting contraception
• Age: 18 - 45 years inclusive
• Successful interval insertion of MIRENA
• History of regular cyclic menstrual periods
• Normal or clinically insignificant cervical smear not requiring further follow up

Exclusion Criteria:

• Pregnancy or lactation
• Climacteric symptoms prior to the screening visit
• Known or suspected clinically significant ovarian cysts, endometrial polyps, fibroids, or other genital organ pathology, that, in the opinion of the investigator, may interfere with the assessment of the bleeding profile during the study
• Undiagnosed abnormal genital bleeding
• Current or history of thrombembolic disease, or established risk factors for venous thromboembolism
• Current migraine, focal migraine with asymmetrical visual loss or other symptoms indicating transient cerebral ischemia, or exceptionally severe headaches
• Hypersensitivity to any ingredient of the investigational medicinal products or the non-investigational medicinal product
• Daily or frequent use of a nonsteroidal anti-inflammatory drug (NSAIDs) for any condition
• Not willing to use nonsteroidal anti-inflammatory drug (NSAIDs) medication as pain medication during the double blind treatment period

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 45 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Denmark, Ireland, Norway

Administrative Information

• NCT Number: NCT01295294
• Other Study ID Numbers: 15105; 2010-020922-16 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Bayer
• Study Sponsor: Bayer
• Collaborators: Not Provided

Investigators

• Study Director: Bayer Study Director; Bayer

• PRS Account: Bayer
• Verification Date: November 2014