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Comparison of Bleeding Risk Between Rivaroxaban and Apixaban for the Treatment of Acute Venous Thromboembolism

PHASE4RECRUITING

Apixaban and rivaroxaban have been compared to standard therapy for treatment of acute symptomatic venous thromboembolism (VTE) in randomized controlled trials (RCTs), and are both approved by Health Canada. No safety or efficacy data is available from direct head-to-head comparison of these two anticoagulants. Lawsuits in the United States over bleeding events, patient perceptions, and concerns with medication adherence are additional factors highlighting the importance of a comparison trial.

This multi-center, pragmatic, prospective, randomized, open-label, blinded end-point (PROBE) trial aims to compare the safety of apixaban and rivaroxaban for the treatment of VTE.

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Study details:

VTE is the third leading cause of mortality by cardiovascular disease. Standard treatment for acute VTE uses a combination of parenteral Low-Molecular-Weight Heparin (LMWH) and oral vitamin K antagonists (VKA) for 3 months, and carries significant bleeding risk. The major and/or clinically-relevant non-major bleeding (CRNMB) event rate is reported between 8.

1-9. 7% during initial treatment. This treatment is burdensome owing to subcutaneous injections, drug interactions, and laboratory monitoring.

Direct oral anticoagulants (DOACs) are simpler to use and do not require laboratory monitoring. Rivaroxaban and apixaban are two DOACs targeting Factor Xa. Each DOAC was separately proven effective and safe when compared to standard treatment.

Comparison of the bleeding rates between studies would favour use of apixaban over rivaroxaban; however, trial limitations and lack of direct comparison between these two agents makes it impossible to draw firm conclusions. This represents a dilemma in clinical practice because the absence of convincing differences in safety has led to genuine uncertainty about which DOAC has the best risk-to-benefit ratio. To address these limitations, a head-to-head randomized controlled trial (RCT) is needed to determine the safety (i.

e. bleeding risk) of twice daily apixaban over once daily rivaroxaban during the first 3 months of acute VTE treatment. Eligibility criteria will be less stringent than the COBRRA pilot study and reflect real-world patients.

Cost-effective analysis of apixaban twice daily compared to rivaroxaban once daily will also be performed.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  • Confirmed newly diagnosed symptomatic acute venous thromboembolism (VTE) [proximal lower extremity deep vein thrombosis (DVT) or segmental or greater pulmonary embolism (PE)]
  • Age ≥ 18 years old
  • Informed consent obtained
  • Exclusion criteria

  • Have received > 72 hours of therapeutic anticoagulation
  • Creatinine clearance < 30 ml/min calculated with the Cockcroft-Gault formula
  • Any contraindication for anticoagulation with apixaban or rivaroxaban as determined by the treating physician such as, but not limited to:
  • active bleeding
  • active malignancy, defined as a) diagnosed with cancer within the past 6 months; or b) recurrent, regionally advanced or metastatic disease; or c) currently receiving treatment or have received any treatment for cancer during the 6 months prior to randomization; or d) a hematologic malignancy not in complete remission
  • weight > 120 kg
  • liver disease (Child-Pugh Class B or C)
  • use of contraindicated medications
  • another indication for long-term anticoagulation (e.g. atrial fibrillation)
  • pregnant (note below) or breastfeeding (Note: as reported by the patient or a pregnancy test will be ordered at the discretion of the treating physician for women of childbearing potential as per standard of care)
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    Eligibility

    Age eligible for study : 18 and older

    Healthy volunteers accepted : No

    Gender eligible for study: All

    Things to know

    Study dates

    Study start: 2017-12-13

    Primary completion: 2024-12-31

    Study completion finish: 2024-12-31

    study type

    Study type

    TREATMENT

    phase

    Phase

      PHASE4

    trial

    Trial ID

    NCT03266783

    Intervention or treatment

    DRUG: Apixaban

    DRUG: Rivaroxaban

    Conditions

    • Venous Thromboembolism

    Find a site

    Closest Location:

    The University of Sydney

    Research sites nearby

    Select from list below to view details:

    • The University of Sydney

      Darlington, New South Wales, Australia

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    Study Plan

    This section provides details of the study plan, including how the study is designed and what the study is measuring.

    How is the study designed?

    Participant Group/ArmIntervention/Treatment
    ACTIVE_COMPARATOR: Apixaban group
    • 10 mg orally (PO), twice a day (BID) for 1 week, then 5 mg PO BID for 3 months of treatment
    DRUG: Apixaban
    • Refer to Apixaban group
    ACTIVE_COMPARATOR: Rivaroxaban group
    • 15 mg orally (PO), twice a day (BID) for 3 weeks, then 20 mg PO once a day (OD) for 3 months of treatment
    DRUG: Rivaroxaban
    • Refer to Rivaroxaban group

    What is the study measuring?

    Primary outcome

    Primary Outcome MeasurePrimary Outcome DescriptionPrimary Outcome Time Frame
    The rate of adjudicated clinically relevant bleeding (CRB) eventsCRB events are defined as the composite of major bleeding (MB) events and clinically relevant non-major bleeding (CRNMB) events.For the duration of the study: 3 months

    Secondary outcome

    Secondary Outcome MeasureSecondary Outcome DescriptionSecondary Outcome Time Frame
    Adjudicated Major Bleeding eventsNot SpecifiedFor the duration of the study: 3 months
    Adjudicated Clinically Relevant Non-Major Bleeding eventsNot SpecifiedFor the duration of the study: 3 months
    Adjudicated recurrent VTE eventsNot SpecifiedFor the duration of the study: 3 months
    Adjudicated VTE-related deathsNot SpecifiedFor the duration of the study: 3 months
    All-cause mortalityNot SpecifiedFor the duration of the study: 3 months
    Medication adherenceNot SpecifiedFor the duration of the study: 3 months
    Quality-adjusted life years (QALYs) gainedNot SpecifiedFor the duration of the study: 3 months
    Incremental cost-effectiveness ratioNot SpecifiedFor the duration of the study: 3 months
    Impact of verbal consent on patient participation in comparison with participants from sites using written informed consentNot SpecifiedFor the duration of the study: 3 months

    Frequently Asked Questions

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    References

    Clinical Trials Gov: Comparison of Bleeding Risk Between Rivaroxaban and Apixaban for the Treatment of Acute Venous Thromboembolism

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