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

NCT04979780 | Completed

• 1 other identifier: 21982
• Study Type: observational
• Target: 3,708
• Locations: 1 country
• Sites: 1

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).

Conditions

Treatment of Venous Thromboembolism in Cancer Patients; Prophylaxis of Recurrent Venous Thromboembolism in Cancer Patients

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (13)

• 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

  at 6 and 12 months post-index VTE

• Any clinically-relevant bleeding-related hospitalization

  at 6 and 12 months

• Intracranial hemorrhage (ICH)

  at 3, 6 and 12 months

• Critical organ bleeding

  at 3, 6 and 12 months

Study Arms (1)

Cancer patients with acute venous thromboembolism (VTE)

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); Drug: Low molecular weight heparin (LMWH); Drug: Direct Oral Anticoagulants (DOAC)

Interventions

Rivaroxaban (Xarelto, BAY59-7939) DRUG

Retrospective cohort analysis using US Optum De-Identified EHR data.

Cancer patients with acute venous thromboembolism (VTE)

Low molecular weight heparin (LMWH) DRUG

Retrospective cohort analysis using US Optum De-Identified EHR data. LMWH (dalteparin, enoxaparin, tinzaparin)

Cancer patients with acute venous thromboembolism (VTE)

Direct Oral Anticoagulants (DOAC) DRUG

Retrospective cohort analysis using US Optum De-Identified EHR data. DOAC (apixaban, dabigatran, edoxaban, rivaroxaban).

Cancer patients with acute venous thromboembolism (VTE)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• 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).

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (1)

Many Locations

Multiple Locations, Connecticut, 06093, United States

Location

Related Publications (2)

• 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.

  PMID: 37435565 BACKGROUND

• Coleman CI, Caroti KS, Abdelgawwad K, Psaroudakis G, Fatoba S, Rivera M, Schaefer B, Brobert G, Khorana AA, Becattini C, Lee AYY, Ekbom A, Carrier M, Brescia C, Cohen AT. Effectiveness and Safety of Rivaroxaban and Low Molecular Weight Heparin in Cancer-Associated Venous Thromboembolism. JACC CardioOncol. 2023 Feb 7;5(2):189-200. doi: 10.1016/j.jaccao.2022.10.014. eCollection 2023 Apr.

  PMID: 37144109 DERIVED

Related Links

• Click here to find further information and, after study completion, the study results according to Bayer's transparency standards

MeSH Terms

Interventions

Rivaroxaban; Heparin, Low-Molecular-Weight; N(4)-oleylcytosine arabinoside

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2021
• First Posted: July 28, 2021
• Study Start: July 20, 2021
• Primary Completion: March 31, 2022
• Study Completion: March 31, 2022
• Last Updated: October 31, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)