Comparison of Bleeding Risk Between Rivaroxaban and Apixaban for the Treatment of Acute Venous Thromboembolism (COBRRA)
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT03266783 |
Recruitment Status :
Recruiting
First Posted : August 30, 2017
Last Update Posted : March 15, 2022
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Venous Thromboembolism | Drug: Apixaban Drug: Rivaroxaban | Phase 4 |
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.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 2760 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Comparison of Bleeding Risk Between Rivaroxaban and Apixaban for the Treatment of Acute Venous Thromboembolism |
Actual Study Start Date : | December 13, 2017 |
Estimated Primary Completion Date : | June 2023 |
Estimated Study Completion Date : | December 2023 |
Arm | Intervention/treatment |
---|---|
Active Comparator: Apixaban group
10 mg PO BID for 1 week, then 5 mg PO BID for 3 months of treatment
|
Drug: Apixaban
Refer to Apixaban group
Other Name: Eliquis |
Active Comparator: Rivaroxaban group
15 mg PO BID for 3 weeks, then 20 mg PO OD for 3 months of treatment
|
Drug: Rivaroxaban
Refer to Rivaroxaban group
Other Name: Xarelto |
- The rate of adjudicated clinically relevant bleeding (CRB) events [ Time Frame: For the duration of the study: 3 months ]CRB events are defined as the composite of major bleeding (MB) events and clinically relevant non-major bleeding (CRNMB) events.
- Adjudicated Major Bleeding events [ Time Frame: For the duration of the study: 3 months ]
- Adjudicated Clinically Relevant Non-Major Bleeding events [ Time Frame: For the duration of the study: 3 months ]
- Adjudicated recurrent VTE events [ Time Frame: For the duration of the study: 3 months ]
- Adjudicated VTE-related deaths [ Time Frame: For the duration of the study: 3 months ]
- All-cause mortality [ Time Frame: For the duration of the study: 3 months ]
- Medication adherence [ Time Frame: For the duration of the study: 3 months ]
- Quality-adjusted life years (QALYs) gained [ Time Frame: For the duration of the study: 3 months ]
- Incremental cost-effectiveness ratio [ Time Frame: 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 [ Time Frame: For the duration of the study: 3 months ]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Confirmed newly diagnosed symptomatic acute VTE (proximal power extremity DVT or segmental or greater 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)

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03266783
Contact: Lana Castellucci, MD, FRCPC | 613-737-8899 ext 74641 | lcastellucci@toh.ca | |
Contact: Veronica Bates, BSc, CCRP | 613-737-8899 ext 71068 | vebates@ohri.ca |

Principal Investigator: | Lana Castellucci, MD, FRCPC | Ottawa Hospital Research Institute |
Responsible Party: | Ottawa Hospital Research Institute |
ClinicalTrials.gov Identifier: | NCT03266783 |
Other Study ID Numbers: |
COBRRA |
First Posted: | August 30, 2017 Key Record Dates |
Last Update Posted: | March 15, 2022 |
Last Verified: | March 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Undecided |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Thromboembolism Venous Thromboembolism Embolism and Thrombosis Vascular Diseases Cardiovascular Diseases Rivaroxaban Apixaban |
Factor Xa Inhibitors Antithrombins Serine Proteinase Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anticoagulants |