Treatment of Heavy Menstrual Bleeding in Women With Uterine Fibroids

• Sponsor: Shannon K. Laughlin-Tommaso (Other)
• Overall Status: Completed
• CT.gov ID: NCT03317795
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
• Enrollment: 18
• Locations: 2
• Arms: 2
• Actual Duration (Months): 37.5
• Patients Per Site: 9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a randomized controlled trial (RCT) to assess the comparative effectiveness of Levonorgestrel Intrauterine System (LNG-IUS) to Tranexamic Acid (TA) for the treatment of heavy menstrual bleeding (HMB) in women with clinically-significant fibroids.

Condition or Disease	Intervention/Treatment	Phase
Heavy Menstrual Bleeding; Menorrhagia; Uterine Fibroids	Drug: Levonorgestrel IUS; Drug: Tranexamic Acid	Phase 4

Detailed Description

Uterine fibroids are common and debilitating problem for some women. Nearly 60% of women with fibroids report that symptoms affect their quality of life and impede physical activity, and 24% report that fibroid symptoms prevent them from reaching their true potential at work. Heavy menstrual bleeding, the most common symptom of uterine fibroids, affects approximately 1.4 million women per year.

Medical therapy is the first line treatment for heavy menstrual bleeding, but further studies need to be done to prove the effectiveness of these treatments.

The goal of this study is to determine the effectiveness of non-estrogenic medical therapy in women with a range of fibroid sizes, locations, and number.

Two effective medical treatments for heavy menstrual bleeding have limited data in women with fibroids. The Levonorgestrel intrauterine system was FDA approved for the treatment of heavy menstrual bleeding in 2009 and is highly effective for decreasing menstrual bleeding, treating anemia and improving quality of life. Moreover, it can be used continuously for 5 years. Tranexamic Acid is widely used outside the U.S. and was also FDA approved for heavy menstrual bleeding in 2009. Tranexamic Acid reduces menstrual blood loss in 40% of women and improves quality of life. In women with fibroids, Tranexamic Acid has been shown to decrease heavy menstrual bleeding and cause necrosis of the fibroids, especially larger fibroids, which should improve its efficacy for women with fibroids.

This randomized controlled trial will assess the comparative effectiveness of Levonorgestrel intrauterine system to Tranexamic Acid for the treatment of heavy menstrual bleeding in women with uterine fibroids

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Prospective Randomized Trial of Tranexamic Acid Versus Levonorgestrel Intrauterine System for the Treatment of Heavy Menstrual Bleeding in Women With Uterine Fibroids
• Actual Study Start Date: Nov 14, 2017
• Actual Primary Completion Date: Dec 28, 2020
• Actual Study Completion Date: Dec 28, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Levonorgestrel IUS Levonorgestrel-releasing intrauterine system (Mirena) contains 52 mg of levonorgestrel, a progestin, and is intended to provide an initial release of approximately 20 mcg/day. Levonorgestrel intrauterine system is effective immediately upon placement in the uterus and can be kept in place for up to 5 years.	Drug: Levonorgestrel IUS; LNG-IUS was FDA-approved for the treatment of heavy menstrual bleeding in 2009 and previously for contraception in 2000. The LNG-IUS is a T-shaped device with a polyethylene body containing a hormone reservoir, holding a total of 52 mg of levonorgestrel. LNG-IUS initially releases 20 micrograms of the progestin per day, which decreases to less than half that amount after 5 years of use. The levonorgestrel causes stromal pseudodecidualization, decreases endometrial thickness, and lowers uterine vascular density.; Other Names: Mirena IUS
Active Comparator: Tranexamic Acid Tranexamic Acid (Lysteda) is an antifibrinolytic drug. Tranexamic Acid will be dosed at 1300mg by mouth three times a day at the start of menses and used during the days that bleeding is heaviest (not to exceed 5 days per menstrual cycle).	Drug: Tranexamic Acid; Tranexamic Acid was FDA-approved for the treatment of heavy menstrual bleeding in 2009. Tranexamic Acid is a plasminogen-activator inhibitor that blocks fibrinolysis and reduces plasmin activity. A special formulation was designed for the treatment of heavy menstrual bleeding that reduces gastrointestinal side effects, brand name Lysteda which will be prescribed as 1300 mg to be taken three times per day for up to 5 days of the menstrual period.; Other Names: Lysteda

Outcome Measures

Primary Outcome Measures

1. Change in Self-Reported Menorrhagia Scores [Baseline, 3 months]

   The Menorrhagia Multi-Attribute Scale (MMAS) questionnaire captures the subjective consequences of menorrhagia on six domains: practical difficulties; social life; psychological wellbeing; physical health; work routine; and family life. Each of the six domains has four statements that represent four levels of response. Respondents indicate the statement that best matches their feelings for each domain. The statement scores derive from a weighting of the domains and a weighting of the statements in level of severity by women in the original study. Scores range from 0 (worst possible state in all domains) to 100 (best possible state in all domains).

2. Number of Participants to Complete Study [9 months]

   Total number of study participants to complete assigned treatment.

Secondary Outcome Measures

1. Change in Pain Score [Baseline, 3 months]

   Pain will be measured by a 10 cm visual analog scale (VAS) which uses a 100 point score, with 0 indicating no pain and 100 indicating worst pain ever. Change was determine by subtracting the 3 month score from baseline, a negative score indicates a decrease in pain.

2. Change in Quality of Life [Baseline, 3 months]

   Measured by the RAND 36-Item Health Survey (Version 1.0). Physical function and mental well-being on scale range from 0-100. A high score defines a more favorable health state.

3. Change in Quality of Life, as Measured by the Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL) [Baseline, 3 months]

   The Uterine Fibroid Symptom and Health Related Quality of Life (HRQL) Questionnaire consists of an 8-item symptom severity scale and 29 HRQL items comprising 6 domains: Concern, Activities, Energy/Mood, Control, Self-consciousness, and Sexual Function. All items are scored on a 5-point Likert scale, ranging from "not at all" to "a very great deal" for symptom severity items and "none of the time" to "all of the time" for the HRQL items. Symptom severity and HRQL subscale scores are summed and transformed into a 0-100 point scale. Higher HRQL subscale scores indicate better HRQL.

4. Change in Symptoms, as Measured by the Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL) [Baseline, 3 months]

   The Uterine Fibroid Symptom and Health Related Quality of Life (HRQL) Questionnaire consists of an 8-item symptom severity scale and 29 HRQL items comprising 6 domains: Concern, Activities, Energy/Mood, Control, Self-consciousness, and Sexual Function. All items are scored on a 5-point Likert scale, ranging from "not at all" to "a very great deal" for symptom severity items and "none of the time" to "all of the time" for the HRQL items. Symptom severity and HRQL subscale scores are summed and transformed into a 0-100 point scale. Higher Symptom Severity scores indicating greater symptoms.

5. Change in Fibroid Size [9 months]

   Fibroid size will be reported as millimeters (mm).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 25 Years to 50 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Premenopausal women ages 25 -50

• Monthly menses

• Image-confirmed uterine fibroids of at least 1 cm in size, either submucosal or intramural

• Seeking treatment for heavy menstrual bleeding following completed clinical evaluation

• Self-reported heavy menstrual bleeding for three months or longer

• Completed evaluation for heavy menstrual bleeding within one year of study enrollment

• Understands the English language for consent and questionnaires

• Able and willing to provide informed consent

Exclusion Criteria:

• Class 0 fibroids confirmed by hysteroscopy, saline-infused sonogram, or 3D ultrasound

• Uterine sounding length ≥ 14 cm

• Uterine size ≥ 20 weeks gestational size

• Abnormal endometrial biopsy or incomplete clinical testing to rule out malignancy

• Needs or is using hormonal contraception, including estrogen-containing medications

• Venous thromboembolic history, clotting disorder, or strong family history of venous thromboembolic events

• Breast, uterine, or cervical malignancy

• Liver disease or liver tumor

• Pelvic inflammatory disease, gonorrhea or chlamydia infection during the past three months

• Hemoglobin < 8 mg/dL. For women with hemoglobin 8.0 - 12.0 mg/dL, iron supplement is recommended

• Serum creatinine ≥ 1.4

• Current pregnancy or currently lactating

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Jacksonville, Florida	Jacksonville	Florida	United States	32224
2	Mayo Clinic in Rochester, Minnesota	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Shannon K. Laughlin-Tommaso
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: Shannon K Laughlin-Tommaso, MD, MPH, Mayo Clinic
• Principal Investigator: Christopher C Destephano, MD, MPH, Mayo Clinic

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 26, 2019

More Information

Additional Information:

• Mayo Clinic Clinical Trials

Publications

None provided.

• Responsible Party: Shannon K. Laughlin-Tommaso, Associate Professor of Obstetrics and Gynecology, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT03317795
• Other Study ID Numbers: 16-008671; R21HD091337
• First Posted: Oct 23, 2017
• Last Update Posted: Dec 8, 2021
• Last Verified: Nov 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Shannon K. Laughlin-Tommaso, Associate Professor of Obstetrics and Gynecology, Mayo Clinic: Menorrhagia; FIbroids; Menstrual Bleeding; Heavy Bleeding; Menses; Uterine Fibroids
• Additional relevant MeSH terms: Leiomyoma; Myofibroma; Menorrhagia; Hemorrhage; Tranexamic Acid; Levonorgestrel

Study Results

Participant Flow

Arm/Group Title	Levonorgestrel IUS	Tranexamic Acid
Arm/Group Description	Levonorgestrel-releasing intrauterine system (Mirena) contains 52 mg of levonorgestrel, a progestin, and is intended to provide an initial release of approximately 20 mcg/day. Levonorgestrel intrauterine system is effective immediately upon placement in the uterus and can be kept in place for up to 5 years. Levonorgestrel IUS: LNG-IUS was FDA-approved for the treatment of heavy menstrual bleeding in 2009 and previously for contraception in 2000. The LNG-IUS is a T-shaped device with a polyethylene body containing a hormone reservoir, holding a total of 52 mg of levonorgestrel. LNG-IUS initially releases 20 micrograms of the progestin per day, which decreases to less than half that amount after 5 years of use. The levonorgestrel causes stromal pseudodecidualization, decreases endometrial thickness, and lowers uterine vascular density.	Tranexamic Acid (Lysteda) is an antifibrinolytic drug. Tranexamic Acid will be dosed at 1300mg by mouth three times a day at the start of menses and used during the days that bleeding is heaviest (not to exceed 5 days per menstrual cycle). Tranexamic Acid: Tranexamic Acid was FDA-approved for the treatment of heavy menstrual bleeding in 2009. Tranexamic Acid is a plasminogen-activator inhibitor that blocks fibrinolysis and reduces plasmin activity. A special formulation was designed for the treatment of heavy menstrual bleeding that reduces gastrointestinal side effects, brand name Lysteda which will be prescribed as 1300 mg to be taken three times per day for up to 5 days of the menstrual period.
Period Title: Overall Study
STARTED	9	9
COMPLETED	7	2
NOT COMPLETED	2	7

Baseline Characteristics

Arm/Group Title	Levonorgestrel IUS	Tranexamic Acid	Total
Arm/Group Description	Levonorgestrel-releasing intrauterine system (Mirena) contains 52 mg of levonorgestrel, a progestin, and is intended to provide an initial release of approximately 20 mcg/day. Levonorgestrel intrauterine system is effective immediately upon placement in the uterus and can be kept in place for up to 5 years. Levonorgestrel IUS: LNG-IUS was FDA-approved for the treatment of heavy menstrual bleeding in 2009 and previously for contraception in 2000. The LNG-IUS is a T-shaped device with a polyethylene body containing a hormone reservoir, holding a total of 52 mg of levonorgestrel. LNG-IUS initially releases 20 micrograms of the progestin per day, which decreases to less than half that amount after 5 years of use. The levonorgestrel causes stromal pseudodecidualization, decreases endometrial thickness, and lowers uterine vascular density.	Tranexamic Acid (Lysteda) is an antifibrinolytic drug. Tranexamic Acid will be dosed at 1300mg by mouth three times a day at the start of menses and used during the days that bleeding is heaviest (not to exceed 5 days per menstrual cycle). Tranexamic Acid: Tranexamic Acid was FDA-approved for the treatment of heavy menstrual bleeding in 2009. Tranexamic Acid is a plasminogen-activator inhibitor that blocks fibrinolysis and reduces plasmin activity. A special formulation was designed for the treatment of heavy menstrual bleeding that reduces gastrointestinal side effects, brand name Lysteda which will be prescribed as 1300 mg to be taken three times per day for up to 5 days of the menstrual period.	Total of all reporting groups
Overall Participants	9	9	18
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.5 (5.6)	44.7 (4.8)	43.6 (5.2)
Sex: Female, Male (Count of Participants)
Female	9 100%	9 100%	18 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Black or African American	2 22.2%	0 0%	2 11.1%
White	6 66.7%	7 77.8%	13 72.2%
Hispanic or Latino	1 11.1%	1 11.1%	2 11.1%
Unknown	0 0%	1 11.1%	1 5.6%
Region of Enrollment (participants) [Number]
United States	9 100%	9 100%	18 100%
Baseline hemoglobin (g/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [g/dL]	12.1 (1.7)	12.22 (1.9)	12.2 (1.8)
Baseline ferritin (mcg/L) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [mcg/L]	6	10	7
Fibroid largest diameter (cm) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [cm]	3.6	2.5	3.5

Outcome Measures

1. Primary Outcome

Title	Change in Self-Reported Menorrhagia Scores
Description	The Menorrhagia Multi-Attribute Scale (MMAS) questionnaire captures the subjective consequences of menorrhagia on six domains: practical difficulties; social life; psychological wellbeing; physical health; work routine; and family life. Each of the six domains has four statements that represent four levels of response. Respondents indicate the statement that best matches their feelings for each domain. The statement scores derive from a weighting of the domains and a weighting of the statements in level of severity by women in the original study. Scores range from 0 (worst possible state in all domains) to 100 (best possible state in all domains).
Time Frame	Baseline, 3 months

Outcome Measure Data

Analysis Population Description

Data was not collected or analyzed for 2 subjects in the Levonorgestrel IUS study arm and 3 subjects in the Tranexamic Acid study arm.

Arm/Group Title	Levonorgestrel IUS	Tranexamic Acid
Arm/Group Description	Levonorgestrel-releasing intrauterine system (Mirena) contains 52 mg of levonorgestrel, a progestin, and is intended to provide an initial release of approximately 20 mcg/day. Levonorgestrel intrauterine system is effective immediately upon placement in the uterus and can be kept in place for up to 5 years. Levonorgestrel IUS: LNG-IUS was FDA-approved for the treatment of heavy menstrual bleeding in 2009 and previously for contraception in 2000. The LNG-IUS is a T-shaped device with a polyethylene body containing a hormone reservoir, holding a total of 52 mg of levonorgestrel. LNG-IUS initially releases 20 micrograms of the progestin per day, which decreases to less than half that amount after 5 years of use. The levonorgestrel causes stromal pseudodecidualization, decreases endometrial thickness, and lowers uterine vascular density.	Tranexamic Acid (Lysteda) is an antifibrinolytic drug. Tranexamic Acid will be dosed at 1300mg by mouth three times a day at the start of menses and used during the days that bleeding is heaviest (not to exceed 5 days per menstrual cycle). Tranexamic Acid: Tranexamic Acid was FDA-approved for the treatment of heavy menstrual bleeding in 2009. Tranexamic Acid is a plasminogen-activator inhibitor that blocks fibrinolysis and reduces plasmin activity. A special formulation was designed for the treatment of heavy menstrual bleeding that reduces gastrointestinal side effects, brand name Lysteda which will be prescribed as 1300 mg to be taken three times per day for up to 5 days of the menstrual period.
Measure Participants	7	6
Median (Inter-Quartile Range) [score on a scale]	59.1	25.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levonorgestrel IUS, Tranexamic Acid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.11
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Primary Outcome

Title	Number of Participants to Complete Study
Description	Total number of study participants to complete assigned treatment.
Time Frame	9 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levonorgestrel IUS	Tranexamic Acid
Arm/Group Description	Levonorgestrel-releasing intrauterine system (Mirena) contains 52 mg of levonorgestrel, a progestin, and is intended to provide an initial release of approximately 20 mcg/day. Levonorgestrel intrauterine system is effective immediately upon placement in the uterus and can be kept in place for up to 5 years. Levonorgestrel IUS: LNG-IUS was FDA-approved for the treatment of heavy menstrual bleeding in 2009 and previously for contraception in 2000. The LNG-IUS is a T-shaped device with a polyethylene body containing a hormone reservoir, holding a total of 52 mg of levonorgestrel. LNG-IUS initially releases 20 micrograms of the progestin per day, which decreases to less than half that amount after 5 years of use. The levonorgestrel causes stromal pseudodecidualization, decreases endometrial thickness, and lowers uterine vascular density.	Tranexamic Acid (Lysteda) is an antifibrinolytic drug. Tranexamic Acid will be dosed at 1300mg by mouth three times a day at the start of menses and used during the days that bleeding is heaviest (not to exceed 5 days per menstrual cycle). Tranexamic Acid: Tranexamic Acid was FDA-approved for the treatment of heavy menstrual bleeding in 2009. Tranexamic Acid is a plasminogen-activator inhibitor that blocks fibrinolysis and reduces plasmin activity. A special formulation was designed for the treatment of heavy menstrual bleeding that reduces gastrointestinal side effects, brand name Lysteda which will be prescribed as 1300 mg to be taken three times per day for up to 5 days of the menstrual period.
Measure Participants	9	9
Count of Participants [Participants]	7 77.8%	2 22.2%

3. Secondary Outcome

Title	Change in Pain Score
Description	Pain will be measured by a 10 cm visual analog scale (VAS) which uses a 100 point score, with 0 indicating no pain and 100 indicating worst pain ever. Change was determine by subtracting the 3 month score from baseline, a negative score indicates a decrease in pain.
Time Frame	Baseline, 3 months

Outcome Measure Data

Analysis Population Description

Data was not collected or analyzed for 2 subjects in the Levonorgestrel IUS study arm and 3 subjects in the Tranexamic Acid study arm.

Arm/Group Title	Levonorgestrel IUS	Tranexamic Acid
Arm/Group Description	Levonorgestrel-releasing intrauterine system (Mirena) contains 52 mg of levonorgestrel, a progestin, and is intended to provide an initial release of approximately 20 mcg/day. Levonorgestrel intrauterine system is effective immediately upon placement in the uterus and can be kept in place for up to 5 years. Levonorgestrel IUS: LNG-IUS was FDA-approved for the treatment of heavy menstrual bleeding in 2009 and previously for contraception in 2000. The LNG-IUS is a T-shaped device with a polyethylene body containing a hormone reservoir, holding a total of 52 mg of levonorgestrel. LNG-IUS initially releases 20 micrograms of the progestin per day, which decreases to less than half that amount after 5 years of use. The levonorgestrel causes stromal pseudodecidualization, decreases endometrial thickness, and lowers uterine vascular density.	Tranexamic Acid (Lysteda) is an antifibrinolytic drug. Tranexamic Acid will be dosed at 1300mg by mouth three times a day at the start of menses and used during the days that bleeding is heaviest (not to exceed 5 days per menstrual cycle). Tranexamic Acid: Tranexamic Acid was FDA-approved for the treatment of heavy menstrual bleeding in 2009. Tranexamic Acid is a plasminogen-activator inhibitor that blocks fibrinolysis and reduces plasmin activity. A special formulation was designed for the treatment of heavy menstrual bleeding that reduces gastrointestinal side effects, brand name Lysteda which will be prescribed as 1300 mg to be taken three times per day for up to 5 days of the menstrual period.
Measure Participants	7	6
Median (Inter-Quartile Range) [units on a scale]	-57.5	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levonorgestrel IUS, Tranexamic Acid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.64
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Secondary Outcome

Title	Change in Quality of Life
Description	Measured by the RAND 36-Item Health Survey (Version 1.0). Physical function and mental well-being on scale range from 0-100. A high score defines a more favorable health state.
Time Frame	Baseline, 3 months

Outcome Measure Data

Analysis Population Description

Data was not collected or analyzed for 2 subjects in the Levonorgestrel IUS study arm and 3 subjects in the Tranexamic Acid study arm.

Arm/Group Title	Levonorgestrel IUS	Tranexamic Acid
Arm/Group Description	Levonorgestrel-releasing intrauterine system (Mirena) contains 52 mg of levonorgestrel, a progestin, and is intended to provide an initial release of approximately 20 mcg/day. Levonorgestrel intrauterine system is effective immediately upon placement in the uterus and can be kept in place for up to 5 years. Levonorgestrel IUS: LNG-IUS was FDA-approved for the treatment of heavy menstrual bleeding in 2009 and previously for contraception in 2000. The LNG-IUS is a T-shaped device with a polyethylene body containing a hormone reservoir, holding a total of 52 mg of levonorgestrel. LNG-IUS initially releases 20 micrograms of the progestin per day, which decreases to less than half that amount after 5 years of use. The levonorgestrel causes stromal pseudodecidualization, decreases endometrial thickness, and lowers uterine vascular density.	Tranexamic Acid (Lysteda) is an antifibrinolytic drug. Tranexamic Acid will be dosed at 1300mg by mouth three times a day at the start of menses and used during the days that bleeding is heaviest (not to exceed 5 days per menstrual cycle). Tranexamic Acid: Tranexamic Acid was FDA-approved for the treatment of heavy menstrual bleeding in 2009. Tranexamic Acid is a plasminogen-activator inhibitor that blocks fibrinolysis and reduces plasmin activity. A special formulation was designed for the treatment of heavy menstrual bleeding that reduces gastrointestinal side effects, brand name Lysteda which will be prescribed as 1300 mg to be taken three times per day for up to 5 days of the menstrual period.
Measure Participants	7	6
Physical Function	11.1	1.7
Mental Well-being	-1.0	3.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levonorgestrel IUS, Tranexamic Acid
	Comments	Physical composite score
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.32
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Levonorgestrel IUS, Tranexamic Acid
	Comments	Mental composite score
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.26
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Secondary Outcome

Title	Change in Quality of Life, as Measured by the Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL)
Description	The Uterine Fibroid Symptom and Health Related Quality of Life (HRQL) Questionnaire consists of an 8-item symptom severity scale and 29 HRQL items comprising 6 domains: Concern, Activities, Energy/Mood, Control, Self-consciousness, and Sexual Function. All items are scored on a 5-point Likert scale, ranging from "not at all" to "a very great deal" for symptom severity items and "none of the time" to "all of the time" for the HRQL items. Symptom severity and HRQL subscale scores are summed and transformed into a 0-100 point scale. Higher HRQL subscale scores indicate better HRQL.
Time Frame	Baseline, 3 months

Outcome Measure Data

Analysis Population Description

Data was not collected or analyzed for 2 subjects in the Levonorgestrel IUS study arm and 3 subjects in the Tranexamic Acid study arm.

Arm/Group Title	Levonorgestrel IUS	Tranexamic Acid
Arm/Group Description	Levonorgestrel-releasing intrauterine system (Mirena) contains 52 mg of levonorgestrel, a progestin, and is intended to provide an initial release of approximately 20 mcg/day. Levonorgestrel intrauterine system is effective immediately upon placement in the uterus and can be kept in place for up to 5 years. Levonorgestrel IUS: LNG-IUS was FDA-approved for the treatment of heavy menstrual bleeding in 2009 and previously for contraception in 2000. The LNG-IUS is a T-shaped device with a polyethylene body containing a hormone reservoir, holding a total of 52 mg of levonorgestrel. LNG-IUS initially releases 20 micrograms of the progestin per day, which decreases to less than half that amount after 5 years of use. The levonorgestrel causes stromal pseudodecidualization, decreases endometrial thickness, and lowers uterine vascular density.	Tranexamic Acid (Lysteda) is an antifibrinolytic drug. Tranexamic Acid will be dosed at 1300mg by mouth three times a day at the start of menses and used during the days that bleeding is heaviest (not to exceed 5 days per menstrual cycle). Tranexamic Acid: Tranexamic Acid was FDA-approved for the treatment of heavy menstrual bleeding in 2009. Tranexamic Acid is a plasminogen-activator inhibitor that blocks fibrinolysis and reduces plasmin activity. A special formulation was designed for the treatment of heavy menstrual bleeding that reduces gastrointestinal side effects, brand name Lysteda which will be prescribed as 1300 mg to be taken three times per day for up to 5 days of the menstrual period.
Measure Participants	7	6
Median (Inter-Quartile Range) [score on a scale]	32.8	21.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levonorgestrel IUS, Tranexamic Acid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.33
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

6. Secondary Outcome

Title	Change in Symptoms, as Measured by the Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL)
Description	The Uterine Fibroid Symptom and Health Related Quality of Life (HRQL) Questionnaire consists of an 8-item symptom severity scale and 29 HRQL items comprising 6 domains: Concern, Activities, Energy/Mood, Control, Self-consciousness, and Sexual Function. All items are scored on a 5-point Likert scale, ranging from "not at all" to "a very great deal" for symptom severity items and "none of the time" to "all of the time" for the HRQL items. Symptom severity and HRQL subscale scores are summed and transformed into a 0-100 point scale. Higher Symptom Severity scores indicating greater symptoms.
Time Frame	Baseline, 3 months

Outcome Measure Data

Analysis Population Description

Data was not collected or analyzed for 2 subjects in the Levonorgestrel IUS study arm and 3 subjects in the Tranexamic Acid study arm.

Arm/Group Title	Levonorgestrel IUS	Tranexamic Acid
Arm/Group Description	Levonorgestrel-releasing intrauterine system (Mirena) contains 52 mg of levonorgestrel, a progestin, and is intended to provide an initial release of approximately 20 mcg/day. Levonorgestrel intrauterine system is effective immediately upon placement in the uterus and can be kept in place for up to 5 years. Levonorgestrel IUS: LNG-IUS was FDA-approved for the treatment of heavy menstrual bleeding in 2009 and previously for contraception in 2000. The LNG-IUS is a T-shaped device with a polyethylene body containing a hormone reservoir, holding a total of 52 mg of levonorgestrel. LNG-IUS initially releases 20 micrograms of the progestin per day, which decreases to less than half that amount after 5 years of use. The levonorgestrel causes stromal pseudodecidualization, decreases endometrial thickness, and lowers uterine vascular density.	Tranexamic Acid (Lysteda) is an antifibrinolytic drug. Tranexamic Acid will be dosed at 1300mg by mouth three times a day at the start of menses and used during the days that bleeding is heaviest (not to exceed 5 days per menstrual cycle). Tranexamic Acid: Tranexamic Acid was FDA-approved for the treatment of heavy menstrual bleeding in 2009. Tranexamic Acid is a plasminogen-activator inhibitor that blocks fibrinolysis and reduces plasmin activity. A special formulation was designed for the treatment of heavy menstrual bleeding that reduces gastrointestinal side effects, brand name Lysteda which will be prescribed as 1300 mg to be taken three times per day for up to 5 days of the menstrual period.
Measure Participants	7	6
Median (Inter-Quartile Range) [score on a scale]	-28.1	-15.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levonorgestrel IUS, Tranexamic Acid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.40
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

7. Secondary Outcome

Title	Change in Fibroid Size
Description	Fibroid size will be reported as millimeters (mm).
Time Frame	9 months

Outcome Measure Data

Analysis Population Description

Data not collected or analyzed for 1 subject in the Tranexamic Acid arm.

Arm/Group Title	Levonorgestrel IUS	Tranexamic Acid
Arm/Group Description	Levonorgestrel-releasing intrauterine system (Mirena) contains 52 mg of levonorgestrel, a progestin, and is intended to provide an initial release of approximately 20 mcg/day. Levonorgestrel intrauterine system is effective immediately upon placement in the uterus and can be kept in place for up to 5 years. Levonorgestrel IUS: LNG-IUS was FDA-approved for the treatment of heavy menstrual bleeding in 2009 and previously for contraception in 2000. The LNG-IUS is a T-shaped device with a polyethylene body containing a hormone reservoir, holding a total of 52 mg of levonorgestrel. LNG-IUS initially releases 20 micrograms of the progestin per day, which decreases to less than half that amount after 5 years of use. The levonorgestrel causes stromal pseudodecidualization, decreases endometrial thickness, and lowers uterine vascular density.	Tranexamic Acid (Lysteda) is an antifibrinolytic drug. Tranexamic Acid will be dosed at 1300mg by mouth three times a day at the start of menses and used during the days that bleeding is heaviest (not to exceed 5 days per menstrual cycle). Tranexamic Acid: Tranexamic Acid was FDA-approved for the treatment of heavy menstrual bleeding in 2009. Tranexamic Acid is a plasminogen-activator inhibitor that blocks fibrinolysis and reduces plasmin activity. A special formulation was designed for the treatment of heavy menstrual bleeding that reduces gastrointestinal side effects, brand name Lysteda which will be prescribed as 1300 mg to be taken three times per day for up to 5 days of the menstrual period.
Measure Participants	7	1
Median (Full Range) [mm]	3	10.5

Adverse Events

Time Frame	Adverse events were collected from baseline to end of study participation for a total of 9 months on all participants.
Arm/Group Title	Levonorgestrel IUS		Tranexamic Acid
Arm/Group Description	Levonorgestrel-releasing intrauterine system (Mirena) contains 52 mg of levonorgestrel, a progestin, and is intended to provide an initial release of approximately 20 mcg/day. Levonorgestrel intrauterine system is effective immediately upon placement in the uterus and can be kept in place for up to 5 years. Levonorgestrel IUS: LNG-IUS was FDA-approved for the treatment of heavy menstrual bleeding in 2009 and previously for contraception in 2000. The LNG-IUS is a T-shaped device with a polyethylene body containing a hormone reservoir, holding a total of 52 mg of levonorgestrel. LNG-IUS initially releases 20 micrograms of the progestin per day, which decreases to less than half that amount after 5 years of use. The levonorgestrel causes stromal pseudodecidualization, decreases endometrial thickness, and lowers uterine vascular density.		Tranexamic Acid (Lysteda) is an antifibrinolytic drug. Tranexamic Acid will be dosed at 1300mg by mouth three times a day at the start of menses and used during the days that bleeding is heaviest (not to exceed 5 days per menstrual cycle). Tranexamic Acid: Tranexamic Acid was FDA-approved for the treatment of heavy menstrual bleeding in 2009. Tranexamic Acid is a plasminogen-activator inhibitor that blocks fibrinolysis and reduces plasmin activity. A special formulation was designed for the treatment of heavy menstrual bleeding that reduces gastrointestinal side effects, brand name Lysteda which will be prescribed as 1300 mg to be taken three times per day for up to 5 days of the menstrual period.
All Cause Mortality
	Levonorgestrel IUS		Tranexamic Acid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/9 (0%)
Serious Adverse Events
	Levonorgestrel IUS		Tranexamic Acid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Levonorgestrel IUS		Tranexamic Acid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/9 (11.1%)		5/9 (55.6%)
Gastrointestinal disorders
Gastrointestinal Disturbance	0/9 (0%)	0	1/9 (11.1%)	1
Nervous system disorders
Headache	0/9 (0%)	0	2/9 (22.2%)	2
Reproductive system and breast disorders
Imbedded IUD	1/9 (11.1%)	1	0/9 (0%)	0
Increased Vaginal Bleeding	0/9 (0%)	0	2/9 (22.2%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.