A Study of Severe Uterine Bleeding Following Exposure to Direct Oral Anticoagulants

Study Overview
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Brief Summary
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The purpose of this study is assess the: (a) incidence of severe uterine bleeding (SUB) following exposure to individual direct oral anticoagulant (DOACs) (rivaroxaban, apixaban, dabigatran) and warfarin, (b) individual DOACs (rivaroxaban, apixaban, dabigatran) association with risk of SUB compared with warfarin, and (c) individual DOACs (rivaroxaban, apixaban, dabigatran) associated with risk of SUB compared with other individual DOACs - among women with prior diagnoses for DOAC and warfarin indications (non-valvular atrial fibrillation [NVAF], venous thromboembolism [VTE], total hip replacement [THR] or total knee replacement [TKR]).

Official Title
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Comparative Risk Assessment of Severe Uterine Bleeding Following Exposure to Direct Oral Anticoagulants: A Network Study Across 4 US Observational Databases

Conditions
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Uterine Hemorrhage

Intervention / Treatment
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* Drug: Direct oral anticoagulant (DOACs)
* Drug: Warfarin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-valvular atrial fibrillation (NVAF) diagnosis any time prior and no Venous thromboembolism (VTE) (Deep vein thrombosis [DVT] or Pulmonary embolism [PE]) in the past 183 days and no knee or hip replacement surgery in the past 35 days VTE (DVT or PE) in the past 183 days and no NVAF diagnosis any time prior and no knee or hip replacement surgery in the past 35 days Total hip replacement (THR) or Total knee replacement (TKR) in the past 35 days and no non-valvular atrial fibrillation any time prior and no venous thromboembolism (deep vein thrombosis of pulmonary embolism) in the past 183 days Exclusion Criteria: Participants were excluded for edoxaban exposure, exposure to other exposures of interest (example: Direct oral anticoagulant [DOACs] for warfarin exposure cohort), hysterectomy, vaginal bleed, and medical, surgical, or transfusion management for vaginal bleeding any time prior to the index exposure

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Treatment Group<br>Participants data who are new users of rivaroxaban, apixaban and dabigatran with prior Non-valvular atrial fibrillation/Venous thromboembolism/Total hip replacement (NVAF/VTE/THR) or Total knee replacement (TKR) in a nationally representative population of insured participants in the United States (US) will be compared pairwise. | Drug: Direct oral anticoagulant (DOACs)<br>* Data of participants newly exposed to individual DOACs that is rivaroxaban, apixaban, dabigatran from 19-Oct-2010 to 31-Dec-2018 will be assessed. No study drug treatment will be administered as part of this observational study.<br>|
| Comparator Group<br>Participants data who are new users of warfarin, apixaban, and dabigatran with prior NVAF/VTE/THR or TKR in a nationally representative population of insured participants in the US will be compared pairwise. | Drug: Direct oral anticoagulant (DOACs)<br>* Data of participants newly exposed to individual DOACs that is rivaroxaban, apixaban, dabigatran from 19-Oct-2010 to 31-Dec-2018 will be assessed. No study drug treatment will be administered as part of this observational study.<br>Drug: Warfarin<br>* Data of participants newly exposed to warfarin from 19-Oct-2010 to 31-Dec-2018 will be assessed. No study drug treatment will be administered as part of this observational study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Severe Uterine Bleed | Number of participants with severe uterine bleed during two time-at-risk periods (on-treatment and all observed time post-index) will be reported. | From 19-Oct-2010 to 31-Dec-2018 |