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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Uterine Hemorrhage	Drug: Tranexamic acid; Drug: Mefenamic acid; Drug: Placebo; Drug: Mirena (Levonorgestrel IUS, BAY86-5028)	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 187 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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.
• Study Start Date: March 2011
• Actual Primary Completion Date: December 2011
• Actual Study Completion Date: December 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: tranexamic acid + Mirena (Levonorgestrel IUS, BAY86-5028); Subjects with successful MIRENA insertion will receive treatments with tranexamic acid	Drug: Tranexamic acid; 500 mg 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
Experimental: mefenamic acid + Mirena (Levonorgestrel IUS, BAY86-5028); Subjects with successful MIRENA insertion will receive treatments with mefenamic acid	Drug: Mefenamic acid; 500 mg 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
Placebo Comparator: placebo + Mirena (Levonorgestrel IUS, BAY86-5028); Subjects with successful MIRENA insertion will receive placebo	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

Outcome Measures

Primary Outcome Measures :

1. The primary efficacy variable will be the cumulative number of bleeding / spotting days [ Time Frame: During 90 day double-blind treatment period ]

Secondary Outcome Measures :

1. To describe and compare the bleeding patterns observed in women during treatment period [ Time Frame: 90 day treatment period ]
2. To describe and compare the bleeding patterns observed in women during follow-up period [ Time Frame: During the 30 day follow-up period ]
3. Satisfaction with oral blinded study drug treatment for bleeding / spotting [ Time Frame: 90 day treatment period ]
4. Occurrence of dysmenorrhea [ Time Frame: During 120 day study period ]
5. Continuation rate with study drug [ Time Frame: During the 90 day treatment period ]
6. Continuation rate with Mirena [ Time Frame: During 120 day study period ]
7. Adverse Events Collection [ Time Frame: Until day 120 ]
8. Number of spotting-only days [ Time Frame: During the 90-day treatment period ]
9. Number of bleeding / spotting episodes [ Time Frame: During the 90-day treatment period ]
10. Length of bleeding / spotting episodes [ Time Frame: During the 90-day treatment period ]
11. Number of bleeding days with heavy intensity [ Time Frame: During the 90-day treatment period ]
12. 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 ]
13. Satisfaction with levonorgestrel-releasing intrauterine system [ Time Frame: Up to day 120 ]
14. Number of days of pain medication for dysmenorrhea during the 90 day treatment period [ Time Frame: During the 90-day treatment period ]
15. Number of bleeding-only days [ Time Frame: During the 90-day treatment period ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

Denmark

København NV, Denmark, DK-2400

Odense C, Denmark, DK-5000

Skive, Denmark, DK-7800

Søborg, Denmark, DK-2860

Ålborg, Denmark, DK-9000

Århus C, Denmark, DK-8000

Ireland

Mallow, Cork, Ireland

Blackrock, Dublin, Ireland

Cork, Ireland

Norway

Elverum, Norway, 2403

Haugesund, Norway, 5507

Trondheim, Norway, 7012

Sponsors and Collaborators

Bayer

Investigators

• Study Director: Bayer Study Director; Bayer

More Information

Additional Information:

Click here and search for information of Bayer products for Europe 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Sordal 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.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT01295294
• Other Study ID Numbers: 15105; 2010-020922-16 ( EudraCT Number )
• First Posted: February 14, 2011
• Last Update Posted: November 4, 2014
• Last Verified: November 2014

Keywords provided by Bayer:

Uterine Hemorrhage; Contraception; Contraceptive Methods; Intrauterine devices; Mirena

Additional relevant MeSH terms:

Uterine Hemorrhage; Hemorrhage; Pathologic Processes; Uterine Diseases; Mefenamic Acid; Tranexamic Acid; Levonorgestrel; Antifibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Hemostatics; Coagulants; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Physiological Effects of Drugs; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Enzyme Inhibitors