Observational Studies in Cancer Associated Thrombosis for Rivaroxaban - United States Cohort

Study Overview
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Brief Summary
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Patients with active cancer are  5-fold more likely to develop a venous thromboembolism (VTE) than those without. When VTE occurs, cancer patients carry an up to a 3-fold higher rate of thrombosis recurrence and  twice the risk of bleeding during anticoagulation. Therefore, it is critical to utilize anticoagulants that optimize efficacy while minimizing bleeding risk when treating cancer-associated thrombosis (CAT). Guidelines list direct-acting oral anticoagulants (DOACs) as an alternative to low molecular-weight heparin (LMWH) for treatment of CAT. The strength-of-recommendation for DOACs is based on data from multiple randomized controlled trials (RCTs) comparing them to LMWHs to treat CAT, with results suggesting DOACs may reduce thrombosis risk but with potentially more frequent bleeding (particularly in those with certain gastrointestinal and genitourinary cancers). Observational studies evaluating DOACs for CAT treatment have been published, but these studies have been either single-arm, evaluated cancer subtypes not recommended for DOAC treatment, were of limited sample size and/or employed heterogeneous definitions of active cancer. We seek to evaluate the effectiveness and safety of rivaroxaban versus LMWH for CAT treatment in active cancer patients using a large de-identified electronic health record database. Retrospective cohort analysis using US Optum® De-Identified EHR data. We will use Optum EHR (electronic health records) data from November January 1, 2012 through latest available data (currently September 2020).

Official Title
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Observational Studies in Cancer Associated Thrombosis for Rivaroxaban - United States Cohort

Conditions
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Treatment of Venous Thromboembolism in Cancer Patients, Prophylaxis of Recurrent Venous Thromboembolism in Cancer Patients

Intervention / Treatment
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* Drug: Rivaroxaban (Xarelto, BAY59-7939)
* Drug: Low molecular weight heparin (LMWH)
* Drug: Direct Oral Anticoagulants (DOAC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be ≥18 years of age at the time of anticoagulation initiation. Have active cancer admitted to the hospital, emergency department or observation unit for acute DVT and/or PE. Treated with rivaroxaban (or any DOAC in secondary analysis) or LMWH as their first anticoagulant on day 7 post-acute CAT event diagnosis (index date) o increase the probability of accurately classifying patients' intended outpatient anticoagulant for CAT treatment and that patients are compared at the same point from diagnosis. Have been active in the data set for at least 12-months prior to the index event (based on the First Month Active field) and had at least one provider visit in the 12-months prior to the acute VTE event (baseline period). Exclusion Criteria: Evidence of atrial fibrillation, recent hip/knee replacement (within 35 days of index VTE), ongoing VTE treatment, valvular heart disease defined as any rheumatic heart disease, mitral stenosis, or mitral valve repair/replacement. Pregnancy. Initiation of rivaroxaban at a dose other than 15 mg twice daily or non-therapeutic doses of other DOAC or LMWH (e.g., enoxaparin at a dose other than 1 mg/kg twice daily or 1.5 mg/kg once daily; dalteparin at a dose other than 200 IU/kg of total body weight) Evidence of use of anticoagulation use during the 12-months prior per written prescription or patient self-report

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cancer patients with acute venous thromboembolism (VTE)<br>Cancer-associated thrombosis (CAT) patients treated with Rivaroxaban or any DOAC (Direct Oral Anticoagulants) or LMWH (Low molecular weight heparin). | Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* Retrospective cohort analysis using US Optum De-Identified EHR data.<br>Drug: Low molecular weight heparin (LMWH)<br>* Retrospective cohort analysis using US Optum De-Identified EHR data. LMWH (dalteparin, enoxaparin, tinzaparin)<br>Drug: Direct Oral Anticoagulants (DOAC)<br>* Retrospective cohort analysis using US Optum De-Identified EHR data. DOAC (apixaban, dabigatran, edoxaban, rivaroxaban).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Risk of recurrent VTE |  | at 3 month after treatment | 
| Any clinically-relevant bleeding-related hospitalization | Cunningham algorithm for identification of bleeding-associated hospitalizations | at 3 month after treatment | 
| All-cause mortality |  | at 3 month after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrent VTE at 6- and 12-months post-index VTE |  | at 6 and 12 months post-index VTE | 
| Composite of any major or clinically-relevant nonmajor bleeding-related hospitalization at 6- and 12-months post-index VTE | including: Intracranial hemorrhage (ICH) Critical organ bleeding (e.g., intracranial, intraspinal, intraocular, retroperitoneal, intraarticular, or pericardial bleeding or intramuscular with compartment syndrome) Extracranial bleeding-related hospitalizations | at 6 and 12 months post-index VTE | 
| Any clinically-relevant bleeding-related hospitalization | per the Cunningham algorithm for identification of bleeding-associated hospitalizations | at 6 and 12 months | 
| Intracranial hemorrhage (ICH) |  | at 3, 6 and 12 months | 
| Critical organ bleeding |  | at 3, 6 and 12 months | 
| Extracranial bleeding-related hospitalizations |  | at 3, 6 and 12 months | 
| All-cause mortality at 6- and 12-months. |  | at 6 and 12 months | 
| Incidence rates of recurrent VTE | Incidence rates of recurrent VTE in DOAC and LMWH patients experiencing CAT regardless of the bleeding risk associated with cancer type. | at 3, 6 and 12 months | 
| Incidence rates any clinically-relevant bleeding-related to recurrent VTE | Incidence rates of any clinically-relevant bleeding-related in DOAC and LMWH patients experiencing CAT regardless of the bleeding risk associated with cancer type. | at 3, 6 and 12 months | 
| All cause-mortality | Incidence rates of all cause-mortality in DOAC and LMWH patients experiencing CAT regardless of the bleeding risk associated with cancer type. | at 3, 6 and 12 months | 
| Duration of anticoagulation treatment |  | at 3, 6 and 12 months | 
| DOAC discontinuation rates at 3-, 6- and 12-months follow-up |  | at 3, 6 and 12 months | 
| LMWH discontinuation rates at 3-, 6- and 12-months follow-up |  | at 3, 6 and 12 months |