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Venous ThromboembolismPhase 2/3(RAMBLE)NCT02829957

RAMBLE - Rivaroxaban vs. Apixaban for Heavy Menstrual Bleeding

A Phase 2/3 study testing Apixaban and Rivaroxaban in people with Venous Thromboembolism and Menstruation, run by Indiana University at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 50 years, women only
Conditions the study is for
Venous Thromboembolism, Menstruation
What is being tested?
Apixaban and Rivaroxaban
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
2 sitesUnited States
Study dates
Sep 2016to 13 Feb 2020
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Eskenazi Health System

    Indianapolis, Indiana, 46202

  • Indiana University Health Methodist Hospital

    Indianapolis, Indiana, 46202

Other trials in United States

About this study

Official title: 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.

Read the 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.

Being tested
Apixaban, Rivaroxaban
Medical subject headings
Venous Thromboembolism

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ApixabanDrug

    Also called Eliquis

    10mg BID for 7 days, then 5mg BID for three months

  • RivaroxabanDrug

    Also called Xarelto

    15mg BID for 7 days, then 20mg daily for three months

Study groups in NCT02829957
Study groupRoleWhat they receive
RivaroxabanActive comparatorNot described
Receives: Drug: Rivaroxaban
ApixabanActive comparatorNot described
Receives: Drug: Apixaban

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. PBAC Scores

    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

    Measured: 3 months

Secondary outcomes (8)

  1. Number of Participants Who Discontinued Planned Drug Administration

    Measured: 3 months

  2. Number of Patients That Held Drug for Menorrhagia

    Measured: 1, 2, and 3 months

  3. Number of Participants With Major Hemorrhage

    Measured: 3 months

  4. Number of Participants With Venous Thromboembolism (VTE)

    Measured: 3 months

  5. Number of Participants Who Crossed Over to Another Anticoagulant

    Measured: 3 months

  6. Number of Participants With Clinically Relevant Non-major Bleeding

    Measured: 3 months

  7. Hemoglobin Concentration

    Measure Description: Normal hemoglobin range for adult women - 12 - 16 g/dL. Lower levels indicate worse outcomes.

    Measured: 3 months

  8. Physical Component Summary of Standard From 36

    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.

    Measured: 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jul 2016 (estimated)
  2. Study startSep 2016
  3. Primary completion13 Feb 2020
  4. Study completion13 Feb 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02829957
Sponsor's protocol ID
RAMBLE
Acronym
(RAMBLE)
Status last verified
Oct 2023
First submitted
6 Jul 2016
Last updated
13 Nov 2023
Data monitoring committee
Yes

Publications

  • De Crem N, Peerlinck K, Vanassche T, Vanheule K, Debaveye B, Middeldorp S, Verhamme P, Peetermans M. Abnormal uterine bleeding in VTE patients treated with rivaroxaban compared to vitamin K antagonists. Thromb Res. 2015 Oct;136(4):749-53. doi: 10.1016/j.thromres.2015.07.030. Epub 2015 Aug 4.

    PubMed 26272306

  • Myers B, Webster A. Heavy menstrual bleeding on Rivaroxaban - Comparison with Apixaban. Br J Haematol. 2017 Mar;176(5):833-835. doi: 10.1111/bjh.14003. Epub 2016 Mar 11. No abstract available.

    PubMed 26970315

  • Beam DM, Kahler ZP, Kline JA. Immediate Discharge and Home Treatment With Rivaroxaban of Low-risk Venous Thromboembolism Diagnosed in Two U.S. Emergency Departments: A One-year Preplanned Analysis. Acad Emerg Med. 2015 Jul;22(7):788-95. doi: 10.1111/acem.12711. Epub 2015 Jun 25.

    PubMed 26113241

  • Kline JA, Kahler ZP, Beam DM. Outpatient treatment of low-risk venous thromboembolism with monotherapy oral anticoagulation: patient quality of life outcomes and clinician acceptance. Patient Prefer Adherence. 2016 Apr 15;10:561-9. doi: 10.2147/PPA.S104446. eCollection 2016.

    PubMed 27143861

  • Liu Z, Doan QV, Blumenthal P, Dubois RW. A systematic review evaluating health-related quality of life, work impairment, and health-care costs and utilization in abnormal uterine bleeding. Value Health. 2007 May-Jun;10(3):183-94. doi: 10.1111/j.1524-4733.2007.00168.x.

    PubMed 17532811

  • Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Masiukiewicz U, Pak R, Thompson J, Raskob GE, Weitz JI; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013 Aug 29;369(9):799-808. doi: 10.1056/NEJMoa1302507. Epub 2013 Jul 1.

    PubMed 23808982

  • EINSTEIN Investigators; Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, Gallus AS, Lensing AW, Misselwitz F, Prins MH, Raskob GE, Segers A, Verhamme P, Wells P, Agnelli G, Bounameaux H, Cohen A, Davidson BL, Piovella F, Schellong S. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010 Dec 23;363(26):2499-510. doi: 10.1056/NEJMoa1007903. Epub 2010 Dec 3.

    PubMed 21128814

  • EINSTEIN-PE Investigators; Buller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, Chlumsky J, Verhamme P, Wells P, Agnelli G, Cohen A, Berkowitz SD, Bounameaux H, Davidson BL, Misselwitz F, Gallus AS, Raskob GE, Schellong S, Segers A. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012 Apr 5;366(14):1287-97. doi: 10.1056/NEJMoa1113572. Epub 2012 Mar 26.

    PubMed 22449293

  • Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Porcari A, Raskob GE, Weitz JI; AMPLIFY-EXT Investigators. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013 Feb 21;368(8):699-708. doi: 10.1056/NEJMoa1207541. Epub 2012 Dec 8.

    PubMed 23216615

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Apixaban and Rivaroxaban in people with Venous Thromboembolism and Menstruation, run by Indiana University at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PBAC Scores (time frame: 3 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02829957, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2023.

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