Estradiol vs Lysteda in Treatment of Heavy Menstrual Bleeding

Estradiol Versus Tranexamic Acid on the Amount and Duration of Acute Cyclic Heavy Menstrual Bleeding

Treatment with Estradiol is non-inferior to treatment with Tranexamic acid in reducing the amount and duration of menstrual blood loss in women with cyclic heavy menstrual bleeding

Study Overview

• Status: Unknown
• Conditions: Menstrual Cycle and Uterine Bleeding Disorders
• Intervention / Treatment: Drug: Estradiol; Drug: Lysteda

Detailed Description

BACKGROUND: The acute onset of Heavy Menstrual Bleeding (HMB) during menses results in women seeking care in the Emergency Department. The current management of HMB among our residents uses combination oral contraceptives or oral progestins. The residents in the Emergency Department often send women home without any therapeutic intervention. There is no Regulatory Agency approved therapy for acute HMB. The etiology of HMB is not well understood. Two potential causes are changes in endometrial prostaglandins and increased fibrinolytic activity in the endometrium.

Specific Aim 1 is to investigate and compare the effect of oral estradiol compared to tranexamic acid in reducing blood loss and the duration of bleeding during an acute episode HMB.

Specific Aim 2 is to evaluate the effect of estradiol and tranexamic acid on possible causes of the acute HMB by measuring prostaglandins and Plasminogen activator in menstrual effluent at the end of treatment.

METHODS: This is a randomized, double-blind, controlled, parallel-group, non-inferiority trial, with participants between the ages 18 and 45 years, with acute cyclic heavy menstrual bleeding enrolled during an emergency room visit. Participants are randomized to receive 48 hours' treatment with 1.3 mg oral tranexamic acid or 1.0 mg oral estradiol three times a day. The primary endpoint is reduction in the amount of menstrual effluent. Sample size was calculated based on detecting less than 30 ml difference between the mean menstrual blood loss of the two treatment groups. Amount of blood loss is quantified by alkaline hematin method on extraction of menstrual pads and tampons. Secondary outcome is the variation of hemostatic factors in the menstrual effluent in two treatment groups by collecting menstrual effluent and quantitating prostaglandins, Plasminogen activators, Plasminogen activator inhibitors, and vascular endothelial growth factor.

ANTICIPATED OUTCOMES: The investigators anticipate a reduction in mean menstrual blood loss in both treatment groups. Compared with participants treated with estradiol, the group treated with tranexamic acid will not have statistically significant change in reduction of menstrual effluent. We also anticipate changes in different local hemostatic factors in menstrual effluent specific to the treatment arm.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Recruiting
      • Jones Institue Clinical Research Center
      • Contact: Kay I Waud, MD PhD; Phone Number: 3103820090; Email: waduk@evms.edu
      • Principal Investigator: Kay I Waud, MD PhD
    • Norfolk, Virginia, United States, 23507
      • Recruiting
      • Sentara Norfolk General Emergency Department
      • Contact: Micheal Bono, MD; Phone Number: 757-388-4000; Email: m.bono@charter.net
      • Sub-Investigator: Micheal Bono, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Age: between 18-45 years old
• Hemoglobin concentration: less than or equal to 11.5 g/dL, greater than or equal to 8.0 g/dL
• BMI: less than or equal to 35
• Menstrual cycle: previous menstrual cycle interval between 26 to 34 days with less than or equal to 10 days of bleeding
• Contraception: at least two months from implant removal, or six months from their last depo-provera or depo-Lupron injection, or recently(at least 2 months) discontinued oral, patch or intravaginal ring contraceptives
• On cycle day 1-3 of the current menstrual bleeding episode

Exclusion Criteria:

• NSAID, or aspirin containing medications during the 48 hours preceding the current ER visit
• Estrogen or progestin treatment during the 30 days preceding the current ER visit
• Using Paraguard
• Pregnant and or lactating
• History of endometrial ablation
• Women with thromboembolic disease, or coagulopathy
• Women with history of myocardial infarction, or cerebrovascular occlusion
• Uncontrolled high blood pressure (blood pressure greater than 150/90)
• Sensitivity to estrogen, or tranexamic acid

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: estradiol; estradiol PO 0.5mg 2 tabs three times a day for 2 days	Drug: Estradiol
Experimental: Lysteda; Lysteda 650mg PO 2 tabs three times a day for 2 days	Drug: Lysteda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
menstrual blood loss	reduction in mean menstrual blood loss in both treatment groups	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in local hemostatic factors	changes in local, endometrial hemostatic factors in both treatment groups	48 hours

Collaborators and Investigators

• Sponsor: Kay I Waud MD PhD
• Collaborators: American College of Obstetricians and Gynecologists
• Investigators: Principal Investigator: Kay I Waud, MD PhD, Eastern Virginia Medical School department of obstetrics and gynecology

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Anticipated): December 1, 2015
• Study Completion (Anticipated): March 1, 2016

Study Registration Dates

• First Submitted: August 3, 2012
• First Submitted That Met QC Criteria: August 6, 2012
• First Posted (Estimate): August 7, 2012

Study Record Updates

• Last Update Posted (Estimate): February 16, 2015
• Last Update Submitted That Met QC Criteria: February 13, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Keywords: acute cyclical heavy menstrual bleeding
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Uterine Diseases; Hematologic Diseases; Hemorrhagic Disorders; Menstruation Disturbances; Hemostatic Disorders; Blood Coagulation Disorders; Hemorrhage; Menorrhagia; Uterine Hemorrhage; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Estradiol
• Other Study ID Numbers: 12-01-FB-0003