COBRRA Pilot: Comparison of Bleeding Risk Between Rivaroxaban and Apixaban
Study Details
Study Description
Brief 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. 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Apixaban 10 mg PO twice-a-day for 1 week, then 5 mg PO, twice daily for 3 or 6 months of treatment. |
Drug: Apixaban
Other Names:
|
| Active Comparator: Rivaroxaban 15 mg PO twice-a-day for 3 weeks, then 20 mg PO once daily for 3 or 6 months of treatment. |
Drug: Rivaroxaban
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Proportion of patients screened who are eligible to participate in the trial [For the duration of the study 3-6 months]
- Proportion of eligible patients who consent to participate in the trial [For the duration of the study 3-6 months]
- Proportion of patients who attend each follow-up visit [For the duration of the study 3-6 months]
- Proportion of patients completing all required study procedures, per follow-up visit [For the duration of the study 3-6 months]
Secondary Outcome Measures
- Bleeding Events [For the duration of the study 3-6 months]
Major bleeding events, clinically relevant non-major and minor bleeding episodes
- Venous Thromboembolism [For the duration of the study 3-6 months]
Recurrent VTE and VTE related-death
- Death [For the duration of the study 3-6 months]
All-cause mortality rates Individual rates of death related to VTE, cardiovascular disease, bleeding or other causes
- Medication compliance as assessed by study pill count [For the duration of the study 3-6 months]
- Time-to-event analysis [For the duration of the study 3-6 months]
The time-to-first occurrence of secondary outcomes between randomization and end of follow-up
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Confirmed newly diagnosed acute VTE (proximal lower extremity DVT and segmental or greater PE)
-
Age ≥ 18 years old
-
Written informed consent
Exclusion Criteria:
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Any contraindication for anticoagulation such as active bleeding
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Clinically significant liver disease or alanine aminotransferase (ALT) levels ≥ 3 times the upper limit of normal range
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Creatinine clearance < 30 ml/min calculated with the Cockcroft-Gault formula (29)
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Known allergies to either apixaban or rivaroxaban
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Pregnancy
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Use of contraindicated medications with apixaban or rivaroxaban
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Alberta | Edmonton | Alberta | Canada | T6G 2G3 |
| 2 | Hamilton General Hospital | Hamilton | Ontario | Canada | L8L 2X2 |
| 3 | The Ottawa Hospital - General Campus | Ottawa | Ontario | Canada | K1H 8L6 |
| 4 | Hôtel-Dieu de Sherbrooke | Sherbrooke | Quebec | Canada | J1G 2E8 |
Sponsors and Collaborators
- Ottawa Hospital Research Institute
- Canadian Institutes of Health Research (CIHR)
- Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network
Investigators
- Principal Investigator: Lana Castellucci, MD, FRCPC, Ottawa Hospital Research Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- COBRRA Pilot
- 20150574-01H