Venous ThromboembolismPhase 4COBRRA PilotNCT02559856
Comparison of Bleeding Risk Between Rivaroxaban and Apixaban: The Pilot Study
A Phase 4 study testing Apixaban and Rivaroxaban in people with Venous Thromboembolism, run by Ottawa Hospital Research Institute at 4 sites in Canada.
Trial summary
This vanguard pilot study compares rivaroxaban and apixaban, two of the new oral blood thinners for the treatment of blood clots. Half of the patients will receive apixaban and half will receive rivaroxaban. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Venous Thromboembolism
- What is being tested?
- Apixaban and Rivaroxaban
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 71 participants
- Where
- 4 sitesCanada
- Study dates
- May 2016to Feb 2018
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed newly diagnosed acute VTE (proximal lower extremity deep vein thrombosis and segmental or greater pulmonary embolism)
- Age ≥ 18 years old
- Written informed consent
Who cannot join
- Any contraindication for anticoagulation such as active bleeding
- Clinically significant liver disease or alanine aminotransferase (ALT) levels ≥ 3 times the upper limit of normal range
- Creatinine clearance < 30 ml/min calculated with the Cockcroft-Gault formula (29)
- Known allergies to either apixaban or rivaroxaban
- Pregnancy
- Use of contraindicated medications with apixaban or rivaroxaban
- Active malignancy in the last 6 months (excluding localized skin malignancy)
- No private insurance coverage for the study drug or not willing to pay for study drug
Trial locations and contacts
4 sites in 1 country.
Canada4 sites
University of Alberta
Edmonton, Alberta, T6G 2G3
Hamilton General Hospital
Hamilton, Ontario, L8L 2X2
The Ottawa Hospital - General Campus
Ottawa, Ontario, K1H 8L6
Hôtel-Dieu de Sherbrooke
Sherbrooke, Quebec, J1G 2E8
About this study
Official title: Comparison of Bleeding Risk Between Rivaroxaban and Apixaban for the Treatment of Acute Venous Thromboembolism: The Pilot Study
This vanguard pilot study compares rivaroxaban and apixaban, two of the new oral blood thinners for the treatment of blood clots. Half of the patients will receive apixaban and half will receive rivaroxaban. The main objective is to determine the feasibility of patient recruitment and resources required to follow enrolled patients and inform for a larger, multi-centered trial and to assess which one is safer.
Read the detailed description
Recently developed new oral anticoagulants (OAC) overcome some of the limitations of established therapy with vitamin K antagonists (VKA) and low molecular weight heparin (LMWH) for treatment of acute venous thromboembolism (VTE), due to ease of administration and more predictable pharmacokinetic properties. Many clinical questions about the new OAC remain unanswered because there have not been direct head-to-head comparison trials. For example, although studies have shown that rivaroxaban and apixaban are at least as effective and safe as LMWH and VKA, meta-analyses suggest that apixaban may be associated with lower bleeding risk. Concerns about the potential impact of medication non-adherence have been raised. Compliance with twice daily medications (e.g. apixaban) is often worse than once daily medications (e.g. rivaroxaban). Both of these medications are approved by Health Canada for treatment of VTE yet there is genuine uncertainty about which of the two direct OAC confer the best risk-to-benefit ratio.This is a multi-centre, prospective randomized open blinded end-point (PROBE) trial assessing clinical feasibility for a larger multi-centered trial comparing bleeding outcomes using apixaban vs. rivaroxaban for treatment of acute VTE. The primary objective of the study is to determine if it is feasible to conduct a large randomized multicenter trial comparing apixaban vs. rivaroxaban for the treatment of acute VTE. The secondary objectives are to assess safety and superiority of apixaban vs rivaroxaban.
- Conditions
- Venous Thromboembolism
- Being tested
- Apixaban, Rivaroxaban
- Medical subject headings
- Venous Thromboembolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApixabanDrug
Also called Eliquis
RivaroxabanDrug
Also called Xarelto
| Study group | Role | What they receive |
|---|---|---|
| Apixaban | Active comparator | 10 mg PO twice-a-day for 1 week, then 5 mg PO, twice daily for 3 or 6 months of treatment. Receives: Drug: Apixaban |
| Rivaroxaban | Active comparator | 15 mg PO twice-a-day for 3 weeks, then 20 mg PO once daily for 3 or 6 months of treatment. Receives: Drug: Rivaroxaban |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients Screened Who Are Eligible to Participate in the Trial
Assessing clinical feasibility for a larger multi-center trial - number of screened patients versus eligible patients
Measured: For the duration of the study 3-6 months
Number of Eligible Patients Who Consent to Participate in the Trial
Assessing clinical feasibility for a larger multi-center trial - number of eligible patients versus patients who consent to participate
Measured: For the duration of the study 3-6 months
Number of Patients Who Attend Each Follow-up Visit
Assessing clinical feasibility for a larger multi-center trial - number of patients that miss visits versus patients that attend visits.
Measured: For the duration of the study 3-6 months
Number of Patients Completing All Required Study Procedures, Per Follow-up Visit
Assessing clinical feasibility for a larger multi-center trial - number of patients that complete all required procedures/study visits versus patients that do not.
Measured: For the duration of the study, 3-6 months
Secondary outcomes (5)
Number of Participants With Major Bleeding, Clinically Relevant Non-Major, Minor Bleeding, or No Bleeding Events
Number of participants with major bleeding events, clinically relevant non-major bleed events (CRNMB), minor bleeding events, or no bleeding events
Measured: For the duration of the study 3-6 months
Number of Participants With Recurrent VTE
Number of Participants with Recurrent Venous Thromboembolism (VTE)
Measured: For the duration of the study 3-6 months
Number of Participants With All-Cause Mortality
- All-cause mortality rates
- Individual rates of death related to VTE, cardiovascular disease, bleeding or other causes
Measured: For the duration of the study 3-6 months
Mean Percentage of Participant Medication Compliance
A participant's compliance to medication based of "dose-taking", which is defined by the percentage of the prescribed doses of pills actually taken by the patient over the study period. A dose-taking of less than 80% will be considered non-compliant. Dose-taking will be assessed by calculating the percentage of 1) study pill count (percentage will be achieved by reviewing the quantities of the medication prescribed and returned); 2) participant medication diary (participant will self-report dose-taking and missed doses); and 3) electronic prescription bottle cap (eCAP) (using a Medication Event Monitoring System (MEMS), which will record and imprint the time of opening the medication container on multiple occasions, which will be used to calculate doses taken vs. missed doses. This method of recording data on adherence will provide preliminary data about rates of non-compliance and will be compared to the conventional methods of self-reporting and pill count for efficacy and safety).
Measured: For the duration of the study 3-6 months
Time-to-Event Analysis
The time-to-first occurrence of secondary outcomes between randomization and end of follow-up
Measured: For the duration of the study 3-6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2015 (estimated)
- Study startMay 2016
- Primary completionNov 2017
- Study completionFeb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Venous ThromboembolismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 71 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network
- Responsible party
- Sponsor
- Investigators
- Lana Castellucci, MD, FRCPC, Principal investigator, Ottawa Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02559856
- Sponsor's protocol ID
- COBRRA Pilot
- Other IDs
- 20150574-01H
- Acronym
- COBRRA Pilot
- Status last verified
- Sep 2026
- First submitted
- 21 Sep 2015
- Last updated
- 21 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No