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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

TREATMENT

Phase

PHASE4

Trial ID

NCT03266783

Intervention or treatment

DRUG: Apixaban

DRUG: Rivaroxaban

Conditions

• Venous Thromboembolism

Condition: Venous Thromboembolism
DRUG: Apixaban and other drugs
Darlington, New South Wales, Australia
Sponsor: Ottawa Hospital Research Institute

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

Are you running this trial? If you're a clinic or sponsor, you can claim this study. Claim or learn more.

Find a site

Closest Location:

The University of Sydney

Research sites nearby

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The University of Sydney
Darlington, New South Wales, Australia

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/Arm	Intervention/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 Measure	Primary Outcome Description	Primary Outcome Time Frame
The rate of adjudicated clinically relevant bleeding (CRB) events	CRB 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 Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Adjudicated Major Bleeding events	Not Specified	For the duration of the study: 3 months
Adjudicated Clinically Relevant Non-Major Bleeding events	Not Specified	For the duration of the study: 3 months
Adjudicated recurrent VTE events	Not Specified	For the duration of the study: 3 months
Adjudicated VTE-related deaths	Not Specified	For the duration of the study: 3 months
All-cause mortality	Not Specified	For the duration of the study: 3 months
Medication adherence	Not Specified	For the duration of the study: 3 months
Quality-adjusted life years (QALYs) gained	Not Specified	For the duration of the study: 3 months
Incremental cost-effectiveness ratio	Not Specified	For the duration of the study: 3 months
Impact of verbal consent on patient participation in comparison with participants from sites using written informed consent	Not Specified	For 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