search
Back to results

Treatment of Heavy Menstrual Bleeding in Women With Uterine Fibroids

Primary Purpose

Heavy Menstrual Bleeding, Menorrhagia, Uterine Fibroids

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Levonorgestrel IUS
Tranexamic Acid
Sponsored by
Shannon K. Laughlin-Tommaso
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heavy Menstrual Bleeding focused on measuring Menorrhagia, FIbroids, Menstrual Bleeding, Heavy Bleeding, Menses, Uterine Fibroids

Eligibility Criteria

25 Years - 50 Years (Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic in Jacksonville, Florida
  • Mayo Clinic in Rochester, Minnesota

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Levonorgestrel IUS

Tranexamic Acid

Arm 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.

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).

Outcomes

Primary Outcome Measures

Change in Self-Reported Menorrhagia Scores
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).
Number of Participants to Complete Study
Total number of study participants to complete assigned treatment.

Secondary Outcome Measures

Change in Pain Score
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.
Change in Quality of Life
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.
Change in Quality of Life, as Measured by the Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL)
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.
Change in Symptoms, as Measured by the Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL)
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.
Change in Fibroid Size
Fibroid size will be reported as millimeters (mm).

Full Information

First Posted
October 10, 2017
Last Updated
November 12, 2021
Sponsor
Shannon K. Laughlin-Tommaso
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
search

1. Study Identification

Unique Protocol Identification Number
NCT03317795
Brief Title
Treatment of Heavy Menstrual Bleeding in Women With Uterine Fibroids
Official Title
Prospective Randomized Trial of Tranexamic Acid Versus Levonorgestrel Intrauterine System for the Treatment of Heavy Menstrual Bleeding in Women With Uterine Fibroids
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
November 14, 2017 (Actual)
Primary Completion Date
December 28, 2020 (Actual)
Study Completion Date
December 28, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Shannon K. Laughlin-Tommaso
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heavy Menstrual Bleeding, Menorrhagia, Uterine Fibroids
Keywords
Menorrhagia, FIbroids, Menstrual Bleeding, Heavy Bleeding, Menses, Uterine Fibroids

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Levonorgestrel IUS
Arm Type
Active Comparator
Arm 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.
Arm Title
Tranexamic Acid
Arm Type
Active Comparator
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Levonorgestrel IUS
Other Intervention Name(s)
Mirena IUS
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Tranexamic Acid
Other Intervention Name(s)
Lysteda
Intervention Description
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.
Primary Outcome Measure Information:
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
Title
Number of Participants to Complete Study
Description
Total number of study participants to complete assigned treatment.
Time Frame
9 months
Secondary Outcome Measure Information:
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
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
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
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
Title
Change in Fibroid Size
Description
Fibroid size will be reported as millimeters (mm).
Time Frame
9 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shannon K Laughlin-Tommaso, MD, MPH
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Christopher C Destephano, MD, MPH
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Jacksonville, Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Mayo Clinic in Rochester, Minnesota
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials

Learn more about this trial

Treatment of Heavy Menstrual Bleeding in Women With Uterine Fibroids

We'll reach out to this number within 24 hrs