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

NCT03266783 | Completed Phase 4 Results DMC

• 1 other identifier: COBRRA
• Study Type: interventional
• Target: 2,760
• Locations: 3 countries
• Sites: 19

Brief Summary

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.

Conditions

Venous Thromboembolism

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Number of Participants With Adjudicated Major Bleeding Events

  For the duration of the study: 3 months

• Number of Participants With Adjudicated Clinically Relevant Non-Major Bleeding Events

  For the duration of the study: 3 months

• Number of Participants With Adjudicated Recurrent Venous Thromboembolism (VTE) Events

  For the duration of the study: 3 months

• Number of Participants With Adjudicated VTE-Related Deaths

  For the duration of the study: 3 months

• All-cause Mortality

  For the duration of the study: 3 months

Study Arms (2)

Apixaban group

ACTIVE COMPARATOR

10 mg orally (PO), twice a day (BID) for 1 week, then 5 mg PO BID for 3 months of treatment

Drug: Apixaban

Rivaroxaban group

ACTIVE COMPARATOR

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

Interventions

Apixaban DRUG

Refer to Apixaban group

Also known as: Eliquis

Apixaban group

Rivaroxaban DRUG

Refer to Rivaroxaban group

Also known as: Xarelto

Rivaroxaban group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead
• Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (19)

The University of Sydney

Darlington, New South Wales, 200606, Australia

Location

University of Calgary

Calgary, Alberta, Canada

Location

Alberta Health Sciences

Edmonton, Alberta, Canada

Location

St. Paul's Hospital

Vancouver, British Columbia, Canada

Location

QEII Health Science Centre

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

Hamilton General Hospital

Hamilton, Ontario, Canada

Location

Juravinski Hospital

Hamilton, Ontario, Canada

Location

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, Canada

Location

Kingston General Hospital

Kingston, Ontario, Canada

Location

London Health Sciences Center

London, Ontario, N6A 5W9, Canada

Location

The Ottawa Hospital - General Campus

Ottawa, Ontario, K1H 8L6, Canada

Location

UHN - Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

McGill University Health Center

Montreal, Quebec, H4A 3J1, Canada

Location

Hôpital Sacré-Coeur de Montréal

Montreal, Quebec, Canada

Location

St. Mary's Hospital

Montreal, Quebec, Canada

Location

CHU de Québec-Université Laval

Québec, Quebec, Canada

Location

University of Sherbrooke

Sherbrooke, Quebec, Canada

Location

The Royal College of Surgeons in Ireland/Mater Misericordiae University Hospital

Dublin, Ireland

Location

Related Publications (1)

• Castellucci LA, Chen VM, Kovacs MJ, Lazo-Langner A, Greenstreet P, Kahn S, Cote B, Schulman S, de Wit K, Douketis J, Suryanarayan D, Wan T, Yeo E, Le Templier G, Tran HA, Willcox A, Crowther HJ, Prasad R, Shivakumar S, Umana E, Ni Ainle F, Tritschler T, Barco S, Galanaud JP, Blondon M, Baumann Kreuziger L, Solymoss S, Kearon C, Thomas E, Ramsay T, Le Gal G, Rodger M; COBRRA Trial Investigators. Bleeding Risk with Apixaban vs. Rivaroxaban in Acute Venous Thromboembolism. N Engl J Med. 2026 Mar 12;394(11):1051-1060. doi: 10.1056/NEJMoa2510703.

  PMID: 41812192 DERIVED

MeSH Terms

Conditions

Venous Thromboembolism

Interventions

apixaban; Rivaroxaban

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Data were collected for only the first 3 months of therapy; whether the differences in bleeding risk persist beyond this period is unknown. Patients who weighed more than 120 kg or had cancer-associated thrombosis were excluded from the trial. Diversity according to race and ethnic group was limited in the trial population, with approximately 10% of the patients reporting non-White race. The open-label design could have introduced ascertainment bias, although unlikely.

Results Point of Contact

• Title: Dr. Lana Castellucci
• Organization: The Ottawa Hospital Research Institute

lcastellucci@toh.ca

613-737-8899

Study Officials

• Lana Castellucci, MD, FRCPC

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2017
• First Posted: August 30, 2017
• Study Start: December 13, 2017
• Primary Completion: April 30, 2025
• Study Completion: October 15, 2025
• Last Updated: June 24, 2026
• Results First Posted: June 24, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (17); IE (1); AU (1)