Clinical trial NCT02829957
Conditions: Venous Thromboembolism Menstruation
Sponsor: Indiana University
Start date: 2016-09-01; Completion date: 2020-02-13
Enrollment: 19 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

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for VTE with varying degree of HMB, no woman has expressed desire to switch to a VKA even when offered this option (unpublished data).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.

Arms: arm 1: None arm 2: None
Interventions: intervention 1: Apixaban intervention 2: Rivaroxaban
Intervention descriptions: intervention 1: 10mg BID for 7 days, then 5mg BID for three months intervention 2: 15mg BID for 7 days, then 20mg daily for three months

Protocol documents:
Prot_000.pdf: 
V02.09.2021 
Randomized Trial to Test the Effect of Rivaroxaban or Apixaban on Menstrual Blood 
Loss in WomEn (RAMBLE) 
 
NCT02829957 
 
The primary comparison is the frequency of study-defined abnormal uterine bleeding between women 
treated with apixaban, versus women treated with rivaroxaban. The plan was to compare these 
frequencies using 95% confidence intervals for the difference in proportions. 
 

SAP_001.pdf: 
V02.09.2021 
Randomized Trial to Test the Effect of Rivaroxaban or Apixaban on Menstrual Blood 
Loss in WomEn (RAMBLE) 
 
NCT02829957 
 
The primary comparison is the frequency of study-defined abnormal uterine bleeding between women 
treated with apixaban, versus women treated with rivaroxaban. The plan was to compare these 
frequencies using 95% confidence intervals for the difference in proportions.