RAMBLE - Rivaroxaban vs. Apixaban for Heavy Menstrual Bleeding ((RAMBLE))

October 23, 2023 updated by: Jeffrey Kline, Indiana University

Randomized Trial to Test the Effect of Rivaroxaban or Apixaban on Menstrual Blood Loss in Women

A large proportion of women with menstruating potential with newly diagnosed VTE or atrial fibrillation, treated with apixaban will have less menstrual blood loss than patients randomized to rivaroxaban.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Heavy menstrual bleeding (HMB) complicates the treatment of approximately 9-25% of patients treated with orally administered anti-Xa anticoagulants for venous thromboembolism (VTE, including either pulmonary embolism or deep vein thrombosis). In particular, recent evidence has suggested an increase in length and severity of menstrual bleeding for women treated with rivaroxaban, and this effect may be less severe apixaban treatment.(1;2) Increase in uterine bleeding with rivaroxaban has necessitated hysterectomy in rare cases.(3) Other complications of HMB include reduced drug adherence, decreased perception of wellness (quality of life) and anemia.(4;5) The anti-Xa agents may increase HMB more than vitamin K antagonists.(1) However, in the principal investigators' experience treating over 100 women of menstruating age with rivaroxaban for VTE with varying degree of HMB, no woman has expressed desire to switch to a VKA even when offered this option (unpublished data). We have successfully reduced perception of HMB by switching from rivaroxaban to apixaban in six patients. Comparison of published and supplemental data from AMPLIFY and AMPLIFY Extend to EINSTEIN and EINSTEIN extend trials also support a lower rate of uterine bleeding with apixaban compared with rivaroxaban, although exact comparisons are difficult to make.(6;9) Myers et al recently reported a 9.4% rate of HMB with apixaban, compared with a 25% rate of HMB with rivaroxaban.(2) Accordingly, we hypothesize that women with menstruating potential with newly diagnosed VTE or atrial fibrillation/flutter, treated with apixaban will have less menstrual blood loss than patients randomized to rivaroxaban.

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Health Methodist Hospital
      • Indianapolis, Indiana, United States, 46202
        • Eskenazi Health System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 46 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Non-pregnant women, age 18-50

    • For study purposes, evidence of negative pregnancy is accounted for by the treating physician's initiation of treatment with oral anticoagulants
  • Objectively diagnosed VTE or atrial fibrillation/flutter
  • Patient reported active menstruation - does not apply to women who were recently pregnant
  • Clinical plan and patient agreement to treat with oral anticoagulation for 3 months or longer
  • Patients must have a working telephone

Exclusion Criteria:

  • Package insert exclusions for Eliquis (Apixban) or Xarelto (Rivaroxaban): [active pathological bleeding or severe hypersensitivity reaction to XARELTO or ELIQUIS (e.g., anaphylactic reactions)]
  • Plan to become pregnant in the next three months.
  • Concomitant prescribed use of aspirin or thienopyridenes or other platelet inhibiting drugs
  • Plan for surgical hysterectomy or endometrial ablation
  • Known uterine cancer
  • Von Willebrand's disease, or hemophilia
  • Known coagulopathy from liver disease
  • Conditions likely to preclude adherence to study procedures: Active intravenous drug use, known alcoholism, homelessness, or uncontrolled psychiatric illness.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Rivaroxaban
Drug: Rivaroxaban
15mg BID for 7 days, then 20mg daily for three months
Other Names:
  • Xarelto
Active Comparator: Apixaban
Drug: Apixaban
10mg BID for 7 days, then 5mg BID for three months
Other Names:
  • Eliquis

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PBAC Scores
Time Frame: 3 months

Measure Description: A PBAC Score of < 100 indicates a normal menstrual cycle. The lowest possible score would be zero. Higher values indicate worse outcomes. The higher theoretical range value cannot be calculated. The scoring mechanism is as follows;

Towels

  • 1 point for each lightly stained towel
  • 5 points or each moderately soiled towel
  • 20 points if the towel is completely saturated with blood

Tampons

  • 1 point for each lightly stained tampon
  • 5 points for each moderately soiled tampon
  • 10 points if the tampon is completely saturated with blood

Clots

  • 1 point for small clots
  • 5 points for large clots
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Who Discontinued Planned Drug Administration
Time Frame: 3 months
3 months
Number of Patients That Held Drug for Menorrhagia
Time Frame: 1, 2, and 3 months
1, 2, and 3 months
Number of Participants With Major Hemorrhage
Time Frame: 3 months
3 months
Number of Participants With Venous Thromboembolism (VTE)
Time Frame: 3 months
3 months
Number of Participants Who Crossed Over to Another Anticoagulant
Time Frame: 3 months
3 months
Number of Participants With Clinically Relevant Non-major Bleeding
Time Frame: 3 months
3 months
Hemoglobin Concentration
Time Frame: 3 months
Measure Description: Normal hemoglobin range for adult women - 12 - 16 g/dL. Lower levels indicate worse outcomes.
3 months
Physical Component Summary of Standard From 36
Time Frame: 3 months
The RAND 36-Item Health Survey (Version 1.0) taps eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. All items are scored so that a high score defines a more favorable health state. In addition, each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively.
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Indiana University

Investigators

  • Principal Investigator: Jeffrey A Kline, MD, Indiana University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2016

Primary Completion (Actual)

February 13, 2020

Study Completion (Actual)

February 13, 2020

Study Registration Dates

First Submitted

July 6, 2016

First Submitted That Met QC Criteria

July 11, 2016

First Posted (Estimated)

July 12, 2016

Study Record Updates

Last Update Posted (Actual)

November 13, 2023

Last Update Submitted That Met QC Criteria

October 23, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RAMBLE

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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