RAMBLE - Rivaroxaban vs. Apixaban for Heavy Menstrual Bleeding
Purpose
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.
Conditions
- Venous Thromboembolism
- Menstruation
Eligibility
- Eligible Ages
- Between 18 Years and 50 Years
- Eligible Genders
- Female
- Accepts Healthy Volunteers
- No
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 Design
- Phase
- Phase 2/Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Active Comparator Rivaroxaban |
|
|
|
Active Comparator Apixaban |
|
Recruiting Locations
More Details
- NCT ID
- NCT02829957
- Status
- Completed
- Sponsor
- Indiana University
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.