Heavy Menstrual Bleeding Progestin Treatment in Bleeding Disorders Study

Study Overview
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Brief Summary
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The goal of this multicenter prospective observational study and registry of U.S. adolescents and young adults with heritable bleeding disorders is to determine the bleeding outcomes, satisfaction, hemostatic parameter changes, and patient reported quality of life after 6 months of use of either of two commonly used hormonal treatments for menstrual suppression - levonorgestrel intrauterine device (LNG-IUD) and norethindrone acetate (NETA). Under this application we will compare the two treatments and compare outcomes after LNG-IUD treatment results to a control group without a bleeding disorder, with the goal of determining the benefits and expected outcomes of these treatment options for this population.

Detailed Description
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Heavy menstrual bleeding (HMB) is common among adolescents and young adults with an inherited bleeding disorder (BD) and negatively impacts health-related quality of life and physical and mental health status. Effective treatment options are available that decrease bleeding and improve quality of life, but were not studied in those with BD, so we do not know if there is similar effectiveness in this condition. We also do not know the impact of treatment on diagnostic testing for BD or on improvement of iron deficiency. Given these gaps in knowledge, the primary objective of the Heavy Menstrual Bleeding Progestin Treatment in Bleeding Disorders Study is to conduct a multicenter prospective observational cohort study and registry, enrolling adolescents and young adults with heavy menstrual bleeding cared for at collaborating interdisciplinary menstrual clinic sites nationally who are choosing to start use of either of two commonly used progestin menstrual treatment options: levonorgestrel-releasing intrauterine system (LNG-IUD) or oral norethindrone acetate 5 mg daily (NETA) (N=300). In Aim 1, we will compare outcomes related to (a) bleeding management, (b) quality of life, and (c) repletion of iron storage levels after six months of treatment with either option in those with a diagnosed inherited bleeding disorder. The primary outcome will be treatment success with a Pictorial Blood Loss Assessment Chart (PBAC) score <50 points by six months. Secondary objectives to assess bleeding management will include need for adjuvant management, change in PBAC from baseline to 6 months, and self-reported treatment success. Quality of life outcomes will include change in validated scales to assess health-related quality of life which are specific to adolescents and young adults in the setting of heavy menstrual bleeding. We will compare ferritin levels at six months compared to baseline to determine the relative amount of benefit obtained from either treatment option. In Aim 2, we will compare outcomes after LNG-IUD in those with and without a bleeding disorder, assessing rates of expulsion and method continuation between the two groups in addition to the outcomes assessed for Aim 1. In Aim 3, we will improve our understanding of the impact of physiological stress on BD diagnostic studies by comparing change in hemostatic parameters before and after successful treatment in those with HMB without a previously diagnosed bleeding disorder. This study will demonstrate the relative benefits of menstrual suppression treatment options for adolescents and young adults with heavy menstrual bleeding and inherited bleeding disorders, will provide population-specific estimates for expected benefit that can be used in treatment counseling, and will highlight the impact of treatment status on diagnostic test results.

Official Title
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Heavy Menstrual Bleeding Progestin Treatment in Bleeding Disorders Study

Conditions
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Heavy Menstrual Bleeding, Bleeding Disorder, Von Willebrand Diseases

Intervention / Treatment
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* Drug: Levonorgestrel Intrauterine System
* Drug: Norethindrone Acetate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Post-menarcheal Ages 10-24 Decision to initiate a trial of progestin therapy with either LNG-IUD or NETA Able to provide assent and written informed consent by one parent (ages <18) or written informed consent (age 18+) Must meet trial criteria for heavy menstrual bleeding Must meet trial criteria for a bleeding disorder or have minimum workup to rule out bleeding disorder Exclusion Criteria: Pregnant or seeking pregnancy

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 24 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Bleeding disorder using LNG-IUD<br>Adolescents and young adults ages 10-24 with diagnosed bleeding disorder planning use of LNG-IUD. | Drug: Levonorgestrel Intrauterine System<br>* 52 mg levonorgestrel intrauterine system<br>* Other names: Liletta;|
| Non-bleeding disorder using LNG-IUD<br>Adolescents and young adults ages 10-24 without diagnosed bleeding disorder planning use of LNG-IUD. | Drug: Levonorgestrel Intrauterine System<br>* 52 mg levonorgestrel intrauterine system<br>* Other names: Liletta;|
| Bleeding disorder using NETA<br>Adolescents and young adults ages 10-24 with diagnosed bleeding disorder planning use of NETA. | Drug: Norethindrone Acetate<br>* norethindrone acetate 5 mg daily<br>* Other names: Aygestin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment success rate | Proportion with pictorial blood loss assessment score <50 points | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median PBAC | Group median of pictorial blood loss assessment score | 6 months | 
| Patient-reported treatment success rate | Proportion with patient-reported treatment success | 6 months | 
| Change in aMBQ score | Group median of individual change in adolescent menstrual bleeding questionnaire score | Baseline to 6 months | 
| Change in PROMIS score | Group median of individual change in patient-reported outcomes measurement information system score | Baseline to 6 months | 
| Change in ferritin | Group median of individual change in ferritin | Baseline to 6 months | 
| Change in von Willebrand Factor (VWF) levels | Group median of individual change in von Willebrand Factor levels | Baseline to 6 months |