Clinical trial NCT04979780: Observational Studies in Cancer Associated Thrombosis for Rivaroxaban - United States Cohort
Official title: Observational Studies in Cancer Associated Thrombosis for Rivaroxaban - United States Cohort
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Treatment of Venous Thromboembolism in Cancer Patients
Prophylaxis of Recurrent Venous Thromboembolism in Cancer Patients
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2021-07-28
Enrollment: 3708
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The Optum EHR database includes longitudinal patient-level medical record data for \~91+ million patients seen at \~700+ hospitals and \~7,000+ clinics across the US. The study population of interest will be patients with cancer, admitted to the hospital, emergency department or observation unit for acute DVT and/or PE on or after January 1, 2013 (to correspond with the US availability of rivaroxaban for VTE treatment), being treated with rivaroxaban (or any DOAC in secondary analysis) or LMWH on day 7 post-acute VTE diagnosis (index date), and 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).

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Risk of recurrent VTE
timeFrame: at 3 month after treatment
measure: Any clinically-relevant bleeding-related hospitalization
timeFrame: at 3 month after treatment
measure: All-cause mortality
timeFrame: at 3 month after treatment
Secondary outcomes:
measure: Recurrent VTE at 6- and 12-months post-index VTE
timeFrame: at 6 and 12 months post-index VTE
measure: Composite of any major or clinically-relevant nonmajor bleeding-related hospitalization at 6- and 12-months post-index VTE
timeFrame: at 6 and 12 months post-index VTE
measure: Any clinically-relevant bleeding-related hospitalization
timeFrame: at 6 and 12 months
measure: Intracranial hemorrhage (ICH)
timeFrame: at 3, 6 and 12 months
measure: Critical organ bleeding
timeFrame: at 3, 6 and 12 months
measure: Extracranial bleeding-related hospitalizations
timeFrame: at 3, 6 and 12 months
measure: All-cause mortality at 6- and 12-months.
timeFrame: at 6 and 12 months
measure: Incidence rates of recurrent VTE
timeFrame: at 3, 6 and 12 months
measure: Incidence rates any clinically-relevant bleeding-related to recurrent VTE
timeFrame: at 3, 6 and 12 months
measure: All cause-mortality
timeFrame: at 3, 6 and 12 months
measure: Duration of anticoagulation treatment
timeFrame: at 3, 6 and 12 months
measure: DOAC discontinuation rates at 3-, 6- and 12-months follow-up
timeFrame: at 3, 6 and 12 months
measure: LMWH discontinuation rates at 3-, 6- and 12-months follow-up
timeFrame: at 3, 6 and 12 months
Other outcomes:
Locations:
city: Multiple Locations
country: United States
facility: Many Locations
state: Connecticut
Study officials:
References:
citation: Caroti KS, Becattini C, Carrier M, Cohen AT, Ekbom A, Khorana AA, Lee AYY, Brescia C, Abdelgawwad K, Psaroudakis G, Rivera M, Schaefer B, Brobert G, Coleman CI. Rivaroxaban versus Apixaban for Treatment of Cancer-Associated Venous Thromboembolism in Patients at Lower Risk of Bleeding. TH Open. 2023 Jul 10;7(3):e206-e216. doi: 10.1055/s-0043-1770783. eCollection 2023 Jul.