A Phase 4 interventional study of Apixaban and Rivaroxaban in Venous Thromboembolism, sponsored by Ottawa Hospital Research Institute. Completed at 19 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-06-24.
Sponsored by Ottawa Hospital Research Institute · Phase 4, Interventional, and Treatment
Among 37 studies testing apixaban in Venous Thromboembolism — 11 open to participants now, 11 under way, 1 of them phase 3. apixaban · Venous Thromboembolism.
Among the 37 studies testing apixaban in Venous Thromboembolism, this one is the 3rd largest by enrollment, is one of 6 that started in 2017, is one of 14 in phase 4, and was the 18th registered.
712 studies on the registry are indexed under Venous Thromboembolism; 146 are open to participants now.
This study's enrollment of 2,760 is above the median of 240 across 401 interventional studies indexed under Venous Thromboembolism.
Browse Venous Thromboembolism studies →11 of the 37 studies testing apixaban in Venous Thromboembolism are open now, in 7 countries. Each count lists the studies.
apixaban: first FDA approval 2012 (ELIQUIS), first EMA approval 2011. What it is approved for, and how studies give it, is on its page →
Of the 113 Venous Thromboembolism studies recruiting now, 90 (80%) set no upper age limit and 13 (12%) stop at 75 or younger; 9 take children under 18; 10 take healthy volunteers.
This study: 18 Years and older · all sexes · no healthy volunteers.
The full table on the hub →37 studies; the count open now beside each. This study's row is marked.
First in 2011; this study’s year is marked. 6 started in 2017.
Median enrollment 100 across the 37 interventional studies. Of the 25 that completed or were terminated, 12 (48%) have results posted.
3 of 37 have an industry lead sponsor. The 10 most frequent:
Ottawa Hospital Research Institute is the lead sponsor of 547 studies on the registry; 99 are open to participants now.
21 studies in Venous Thromboembolism by Ottawa Hospital Research Institute: 6 open now, 6 under way, 5 of them phase 3. Of 12 finished, 4 (33%) have results posted.
Among the 21 studies in Venous Thromboembolism by Ottawa Hospital Research Institute, this one has the largest enrollment of the 15 interventional ones, is the only one that started in 2017, is one of 3 in phase 4, and was the 12th registered.
Ottawa Hospital Research Institute’s Venous Thromboembolism studies by the year they started, since 2002.
7 of the studies testing apixaban in Venous Thromboembolism that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT04874428Insel Gruppe AG, University Hospital BernDirect Oral Anticoagulants (Rivaroxaban and Apixaban) in Patients With Liver Cirrhosis | 2026-12 |
| NCT05683808University of Vermont Medical CenterVenous Thromboembolism Prevention in Outpatients With Glioma | 2026-12-30 |
| NCT07869615Military Hospital of TunisComparison of DOACs and LMWH for Thromboprophylaxis After Total Knee Arthroplasty | 2027-04-15 |
| NCT05735639Imperial College LondonTHRomboprophylaxis in Individuals Undergoing Superficial endoVEnous Treatment (THRIVE) | 2027-06-30 |
| NCT06886516Rushad PatellApixaban in Thrombocytopenia | 2027-07-01 |
Among the 37 studies testing apixaban in Venous Thromboembolism, from their registry updates:
Among Ottawa Hospital Research Institute’s 21 in Venous Thromboembolism:
Nothing recorded among them since 2026-09-25.
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.
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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Any for anticoagulation with apixaban or rivaroxaban as determined by the treating physician such as, but not limited to:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
10 mg orally (PO), twice a day (BID) for 1 week, then 5 mg PO BID for 3 months of treatment
Drug: Apixaban
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 Apixaban group
Also known as: Eliquis
Refer to Rivaroxaban group
Also known as: Xarelto
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.
Time frame: For the duration of the study: 3 months
Number of Participants With Adjudicated Major Bleeding Events
Major bleeding will be defined as fatal bleeding, and/or, Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome, and/or bleeding causing a fall in hemoglobin of ≥20 g/L, or leading to transfusion of ≥2 units of whole blood or red cells.
Time frame: For the duration of the study: 3 months
Number of Participants With Adjudicated Clinically Relevant Non-Major Bleeding Events
Clinically relevant non-major bleeding will be defined as any sign or symptom of hemorrhage (e.g., more bleeding than would be expected for a clinical circumstance, including bleeding found by imaging alone) that does not fit the criteria for the International Society on Thrombosis and Haemostasis (ISTH) definition of major bleeding but does meet at least one of the following criteria: * Requiring medical intervention by a healthcare professional * Leading to hospitalization or increased level of care * Prompting a face to face (i.e., not just a telephone or electronic communication) evaluation
Time frame: For the duration of the study: 3 months
Number of Participants With Adjudicated Recurrent Venous Thromboembolism (VTE) Events
Recurrent VTE will be confirmed with investigational reports including clinic notes, D-dimer results and imaging as per standard of care. Recurrent Deep Vein Thrombosis (DVT) will be confirmed by compression ultrasound revealing a new (compared to baseline/index ultrasound) area of non-compressibility in the popliteal vein or more proximal vein, or venography demonstrating a constant intraluminal filling defect in the popliteal vein or more proximal veins. Recurrent Pulmonary Embolism (PE) will be diagnosed if the Ventilation-Perfusion (VQ) scan is non-normal and a new unmatched segmental or greater perfusion defect is documented, or an intraluminal filling defect is seen on Computed Tomography Pulmonary Angiogram (CTPA) in a segmental or greater vessel that was previously free of thrombus, or pulmonary angiography demonstrating a constant intraluminal filling defect or a cutoff of a vessel \>2.5 mm in diameter will be considered diagnostic for PE.
Time frame: For the duration of the study: 3 months
Number of Participants With Adjudicated VTE-Related Deaths
VTE-related death (fatal PE or unexplained deaths) will be confirmed using death certificates and/or autopsy findings.
Time frame: For the duration of the study: 3 months
All-cause Mortality
Using a binary outcome of an event or no event (Individual rates of death related to VTE, bleeding or other causes).
Time frame: For the duration of the study: 3 months
Medication Adherence
Reported as the number of patients self-reporting full medication adherence.
Time frame: For the duration of the study: 3 months
Quality-Adjusted Life Years (QALYs) Gained
We will measure health utility values using the EQ-5D-5L (EuroQoL-5 Dimension-5 Level) Questionnaire at baseline, 2 week (± 7 days), and 90 days (+14 days). We will model the prognosis of a cohort of patients receiving rivaroxaban as a baseline against the potential impact of apixaban. The results will be presented as incremental cost per QALY gained, incremental costs per one CRB cases prevented, and incremental cost per one life year saved.
Time frame: For the duration of the study: 3 months
Incremental Cost-effectiveness Ratio
Incremental cost-effectiveness ratios including cost per one CRB case prevented, cost per one life year saved, cost per one quality-adjusted life year (QALY) gained, which will be analyzed as part of the health economic analysis plan.
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
Impact of verbal consent on patient participation in comparison with participants from sites using written informed consent. Due to the qualitative nature of this outcome, it will be presented descriptively.
Time frame: For the duration of the study: 3 months
| Milestone | Apixaban Group | Rivaroxaban Group |
|---|---|---|
| Started | 1370 | 1390 |
| Completed | 1345 | 1355 |
| Not completed | 25 | 35 |
CRB events are defined as the composite of major bleeding (MB) events and clinically relevant non-major bleeding (CRNMB) events.
| Participants | Apixaban Group | Rivaroxaban Group |
|---|---|---|
| The Rate of Adjudicated Clinically Relevant Bleeding (CRB) Events | 44 | 96 |
Major bleeding will be defined as fatal bleeding, and/or, Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome, and/or bleeding causing a fall in hemoglobin of ≥20 g/L, or leading to transfusion of ≥2 units of whole blood or red cells.
| Participants | Apixaban Group | Rivaroxaban Group |
|---|---|---|
| Number of Participants With Adjudicated Major Bleeding Events | 5 | 32 |
Clinically relevant non-major bleeding will be defined as any sign or symptom of hemorrhage (e.g., more bleeding than would be expected for a clinical circumstance, including bleeding found by imaging alone) that does not fit the criteria for the International Society on Thrombosis and Haemostasis (ISTH) definition of major bleeding but does meet at least one of the following criteria: * Requiring medical intervention by a healthcare professional * Leading to hospitalization or increased level of care * Prompting a face to face (i.e., not just a telephone or electronic communication) evaluation
| Participants | Apixaban Group | Rivaroxaban Group |
|---|---|---|
| Number of Participants With Adjudicated Clinically Relevant Non-Major Bleeding Events | 39 | 67 |
Recurrent VTE will be confirmed with investigational reports including clinic notes, D-dimer results and imaging as per standard of care. Recurrent Deep Vein Thrombosis (DVT) will be confirmed by compression ultrasound revealing a new (compared to baseline/index ultrasound) area of non-compressibility in the popliteal vein or more proximal vein, or venography demonstrating a constant intraluminal filling defect in the popliteal vein or more proximal veins. Recurrent Pulmonary Embolism (PE) will be diagnosed if the Ventilation-Perfusion (VQ) scan is non-normal and a new unmatched segmental or greater perfusion defect is documented, or an intraluminal filling defect is seen on Computed Tomography Pulmonary Angiogram (CTPA) in a segmental or greater vessel that was previously free of thrombus, or pulmonary angiography demonstrating a constant intraluminal filling defect or a cutoff of a vessel \>2.5 mm in diameter will be considered diagnostic for PE.
| Participants | Apixaban Group | Rivaroxaban Group |
|---|---|---|
| Number of Participants With Adjudicated Recurrent Venous Thromboembolism (VTE) Events | 15 | 14 |
VTE-related death (fatal PE or unexplained deaths) will be confirmed using death certificates and/or autopsy findings.
| Participants | Apixaban Group | Rivaroxaban Group |
|---|---|---|
| Number of Participants With Adjudicated VTE-Related Deaths | 0 | 0 |
Using a binary outcome of an event or no event (Individual rates of death related to VTE, bleeding or other causes).
| Participants | Apixaban Group | Rivaroxaban Group |
|---|---|---|
| All-cause Mortality | 1 | 4 |
Reported as the number of patients self-reporting full medication adherence.
| Participants | Apixaban Group | Rivaroxaban Group |
|---|---|---|
| Medication Adherence | 884 | 1017 |
We will measure health utility values using the EQ-5D-5L (EuroQoL-5 Dimension-5 Level) Questionnaire at baseline, 2 week (± 7 days), and 90 days (+14 days). We will model the prognosis of a cohort of patients receiving rivaroxaban as a baseline against the potential impact of apixaban. The results will be presented as incremental cost per QALY gained, incremental costs per one CRB cases prevented, and incremental cost per one life year saved.
Results for this outcome have not been posted.
Incremental cost-effectiveness ratios including cost per one CRB case prevented, cost per one life year saved, cost per one quality-adjusted life year (QALY) gained, which will be analyzed as part of the health economic analysis plan.
Results for this outcome have not been posted.
Impact of verbal consent on patient participation in comparison with participants from sites using written informed consent. Due to the qualitative nature of this outcome, it will be presented descriptively.
Results for this outcome have not been posted.
Collected over 3 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Apixaban Group | 1/1,345 (0.1%) | 36/1,345 (2.7%) | — |
| Rivaroxaban Group | 4/1,355 (0.3%) | 30/1,355 (2.2%) | — |
| Event | Apixaban Group | Rivaroxaban Group |
|---|---|---|
| Chest pain, myocardial infarction, atrial fibrillation, cardiovascular disease, cardiac arrestCardiac disorders | 10/1345 | 5/1355 |
| Pneumonia, viral infection, appendicitis, fever, empyema, abscess, sepsisInfections and infestations | 6/1345 | 8/1355 |
| Lung cancer, ovarian cancer, pancreatic cancer, lymphoma, adenocarcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 6/1345 | 4/1355 |
| Obstruction, intussusception, hernia, inflammatory bowel syndrome, ischemia, mesenteric thrombosisGastrointestinal disorders | 2/1345 | 5/1355 |
| Headache, limb weakness, neuropathy, strokeNervous system disorders | 4/1345 | 2/1355 |
| Suicidal ideation, hallucinationsPsychiatric disorders | 0/1345 | 3/1355 |
| Electrolyte disturbanceMetabolism and nutrition disorders | 2/1345 | 0/1355 |
| Nephrotic syndromeRenal and urinary disorders | 2/1345 | 0/1355 |
| Allergic reactionImmune system disorders | 1/1345 | 0/1355 |
| Ankle fractureMusculoskeletal and connective tissue disorders | 1/1345 | 0/1355 |
| Age, Continuous(years) | Apixaban Group | Rivaroxaban Group | Total |
|---|---|---|---|
| Mean | 58.0 (18 to 94) | 58.5 (18 to 97) | 58.25 (18 to 97) |
| Sex: Female, Male(Participants) | Apixaban Group | Rivaroxaban Group | Total |
|---|---|---|---|
| Female | 597 | 578 | 1175 |
| Male | 748 | 777 | 1525 |
| Race (NIH/OMB)(Participants) | Apixaban Group | Rivaroxaban Group | Total |
|---|---|---|---|
| American Indian or Alaska Native | 8 | 4 | 12 |
| Asian | 36 | 31 | 67 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 51 | 44 | 95 |
| White | 1182 | 1218 | 2400 |
| More than one race | 4 | 2 | 6 |
| Unknown or Not Reported | 64 | 56 | 120 |
| Region of Enrollment(participants) | Apixaban Group | Rivaroxaban Group | Total |
|---|---|---|---|
| Canada | 1244 | 1254 | 2498 |
| Ireland | 1 | 3 | 4 |
| Australia | 100 | 98 | 198 |
| Body Weight(kg) | Apixaban Group | Rivaroxaban Group | Total |
|---|---|---|---|
| Mean | 85.9 (43 to 120) | 85.2 (37 to 129) | 85.55 (37 to 129) |
| Body Mass Index(kg/m^2) | Apixaban Group | Rivaroxaban Group | Total |
|---|---|---|---|
| Mean | 29.1 (15.4 to 49.3) | 28.9 (14.5 to 48.4) | 29 (14.5 to 49.3) |
| Creatinine Clearance(ml/min) | Apixaban Group | Rivaroxaban Group | Total |
|---|---|---|---|
| Mean | 107.1 (30 to 275) | 105.6 (30 to 314) | 106.35 (30 to 314) |
| Continued Antiplatelet Use(Participants) | Apixaban Group | Rivaroxaban Group | Total |
|---|---|---|---|
| Count of participants | 36 | 35 | 71 |
3 further baseline measures are reported on the registry.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
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Studies of the drugs tested here: Apixaban · Rivaroxaban
Ottawa Hospital Research Institute →