A Phase 3 interventional study of Rivaroxaban (Xarelto, BAY59-7939) and Acetylsalicylic acid (Aspirin, BAY1019036) in Stroke, sponsored by Bayer. Terminated at 454 sites in 31 countries. Open to participants aged 50 Years and older. Per ClinicalTrials.gov, last updated 2019-01-09.
Sponsored by Bayer · Phase 3, Interventional, and Prevention
This is a study in patients who recently had a brain attack (stroke) and in whom no clear cause of the stroke could be identified. These strokes are likely due to a blood clot and therefore, can be called embolic stroke of undetermined source. The abbreviation is ESUS. The study will compare 2 blood thinners. Patients will be randomly assigned to either Rivaroxaban 15 mg or Aspirin 100 mg and the study is intended to show, if patients given rivaroxaban have fewer blood clots in the brain (stroke) or in other blood vessels.
8,255 studies on the registry are indexed under Stroke; 2,056 are open to participants now.
This study's enrollment of 7,213 is above the median of 49 across 6,024 interventional studies indexed under Stroke.
Browse Stroke studies →Bayer is the lead sponsor of 1,674 studies on the registry; 51 are open to participants now.
Of its 214 completed or terminated interventional studies of FDA-regulated products, 132 (62%) have results posted.
Counted across the registry records on this site, refreshed daily.
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:
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.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Rivaroxaban 15 mg orally once daily
Drug: Rivaroxaban (Xarelto, BAY59-7939) · Other: Rivaroxaban-Placebo
Aspirin 100 mg orally once daily
Drug: Acetylsalicylic acid (Aspirin, BAY1019036) · Other: Aspirin-Placebo
15 mg, once daily, orally, tablet
100 mg, once daily, orally, tablet
Matching placebo, once daily, orally, tablet
Matching placebo, once daily, orally, tablet
Incidence Rate of the Composite Efficacy Outcome (Adjudicated)
Components of composite efficacy outcome (adjudicated) includes stroke (ischemic, hemorrhagic, and undefined stroke, TIA with positive neuroimaging) and systemic embolism. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred.
Time frame: From randomization until the efficacy cut-off date (median 326 days)
Incidence Rate of a Major Bleeding Event According to the International Society on Thrombosis and Haemostasis (ISTH) Criteria (Adjudicated)
Major bleeding event (as per ISTH), defined as bleeding event that met at least one of following: fatal bleeding; symptomatic bleeding in a critical area or organ (intraarticular, intramuscular with compartment syndrome, intraocular, intraspinal, pericardial, or retroperitoneal); symptomatic intracranial haemorrhage; clinically overt bleeding associated with a recent decrease in the hemoglobin level of greater than or equal to (\>=) 2 grams per decilitre (g/dL) (20 grams per liter \[g/L\]; 1.24 millimoles per liter \[mmol/L\]) compared to the most recent hemoglobin value available before the event; clinically overt bleeding leading to transfusion of 2 or more units of packed red blood cells or whole blood. The results were based on classification of events that have been positively adjudicated as major bleeding events. Incidence rate estimated as number of subjects with incident events divided by cumulative at-risk time, where subject is no longer at risk once an incident event occurred.
Time frame: From randomization until the efficacy cut-off date (median 326 days)
Incidence Rate of Any of the Following: Cardiovascular Death, Recurrent Stroke, Systemic Embolism and Myocardial Infarction
Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred. Cardiovascular death includes death due to hemorrhage and death with undetermined/unknown cause. Systemic embolism is defined as abrupt vascular insufficiency associated with clinical or radiological evidence of arterial occlusion in the absence of other likely mechanisms. The diagnosis of myocardial infarction requires the combination of: 1)evidence of myocardial necrosis (either changes in cardiac biomarkers or post-mortem pathological findings); and 2)supporting information derived from the clinical presentation, electrocardiographic changes, or the results of myocardial or coronary artery imaging.
Time frame: From randomization until the efficacy cut-off date (median 326 days)
Incidence Rate of All-Cause Mortality
All-cause mortality includes all deaths of participants due to any cause.
Time frame: From randomization until the efficacy cut-off date (median 326 days)
Incidence Rate of the Following: Stroke, Ischemic Stroke, Disabling Stroke, Cardiovascular (CV) Death, Myocardial Infarction
Disabling stroke is defined as stroke with modified Rankin score (mRS) greater than or equal to (\>=) 4 as assessed by investigator. mRS spans 0-6, running from perfect health to death. A score of 0-3 indicates functional status ranging from no symptoms to "moderate disability" (defined in the mRS as requiring some help, but able to walk without assistance); mRS 4-6 indicates functional status ranging from "moderately severe disability" (unable to walk or to attend to own bodily needs without assistance)through to death. CV death includes death due to hemorrhage and death with undetermined/unknown cause. Diagnosis of myocardial infarction requires combination of: 1) evidence of myocardial necrosis either changes in cardiac biomarkers or post-mortem pathological findings); 2) supporting information derived from clinical presentation, electrocardiographic changes, or results of myocardial or coronary artery imaging.
Time frame: From randomization until the efficacy cut-off date (median 326 days)
Incidence Rate of Life-Threatening Bleeding Events
Life-threatening bleeding was defined as a subset of major bleeding that met at least one of the following criteria: 1) fatal bleeding; 2) symptomatic intracranial haemorrhage; 3) reduction in hemoglobin of at least 5 g/dl (50 g/l; 3.10 mmol/L); 4) transfusion of at least 4 units of packed red cells or whole blood; 5) associated with hypotension requiring the use of intravenous inotropic agents; 6) necessitated surgical intervention. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred.
Time frame: From randomization until the efficacy cut-off date (median 326 days)
Incidence Rate of Clinically Relevant Non-Major Bleeding Events
Non-major clinically relevant bleeding was defined as non-major overt bleeding but required medical attention (example: hospitalization, medical treatment for bleeding), and/or was associated with the study drug interruption of more than 14 days. The results were based on the outcome events at or after randomization until the efficacy cut-off date. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred.
Time frame: From randomization until the efficacy cut-off date (median 326 days)
Incidence Rate of Intracranial Hemorrhage
Intracranial hemorrhage included all bleeding events that occurred in intracerebral, sub arachnoidal as well as subdural or epidural sites. The below table displays results for all randomized participants and the outcomes at or after randomization until the efficacy cut-off date. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred.
Time frame: From randomization until the efficacy cut-off date (median 326 days)
Study was conducted at multiple centers in 31 countries between 23 December 2014 (first participant first visit) and 15 February 2018 (last participant last visit).
| Milestone | Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Started | 3609 | 3604 |
| Treated | 3562 | 3559 |
| Completed | 3552 | 3554 |
| Not completed | 57 | 50 |
| Withdrew: Consent withdrawn by participant | 33 | 33 |
| Withdrew: Lost to follow-up | 24 | 17 |
Components of composite efficacy outcome (adjudicated) includes stroke (ischemic, hemorrhagic, and undefined stroke, TIA with positive neuroimaging) and systemic embolism. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred.
| event/100 participant-years | Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Incidence Rate of the Composite Efficacy Outcome (Adjudicated) | 5.14 (4.40 to 5.97) | 4.78 (4.07 to 5.58) |
Major bleeding event (as per ISTH), defined as bleeding event that met at least one of following: fatal bleeding; symptomatic bleeding in a critical area or organ (intraarticular, intramuscular with compartment syndrome, intraocular, intraspinal, pericardial, or retroperitoneal); symptomatic intracranial haemorrhage; clinically overt bleeding associated with a recent decrease in the hemoglobin level of greater than or equal to (\>=) 2 grams per decilitre (g/dL) (20 grams per liter \[g/L\]; 1.24 millimoles per liter \[mmol/L\]) compared to the most recent hemoglobin value available before the event; clinically overt bleeding leading to transfusion of 2 or more units of packed red blood cells or whole blood. The results were based on classification of events that have been positively adjudicated as major bleeding events. Incidence rate estimated as number of subjects with incident events divided by cumulative at-risk time, where subject is no longer at risk once an incident event occurred.
| event/100 participant-years | Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Incidence Rate of a Major Bleeding Event According to the International Society on Thrombosis and Haemostasis (ISTH) Criteria (Adjudicated) | 1.82 (1.39 to 2.33) | 0.67 (0.42 to 1.00) |
Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred. Cardiovascular death includes death due to hemorrhage and death with undetermined/unknown cause. Systemic embolism is defined as abrupt vascular insufficiency associated with clinical or radiological evidence of arterial occlusion in the absence of other likely mechanisms. The diagnosis of myocardial infarction requires the combination of: 1)evidence of myocardial necrosis (either changes in cardiac biomarkers or post-mortem pathological findings); and 2)supporting information derived from the clinical presentation, electrocardiographic changes, or the results of myocardial or coronary artery imaging.
| event/100 participant-years | Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Incidence Rate of Any of the Following: Cardiovascular Death, Recurrent Stroke, Systemic Embolism and Myocardial Infarction | 6.20 (5.38 to 7.10) | 5.85 (5.05 to 6.73) |
All-cause mortality includes all deaths of participants due to any cause.
| event/100 participant-years | Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Incidence Rate of All-Cause Mortality | 1.88 (1.45 to 2.40) | 1.50 (1.12 to 1.97) |
Disabling stroke is defined as stroke with modified Rankin score (mRS) greater than or equal to (\>=) 4 as assessed by investigator. mRS spans 0-6, running from perfect health to death. A score of 0-3 indicates functional status ranging from no symptoms to "moderate disability" (defined in the mRS as requiring some help, but able to walk without assistance); mRS 4-6 indicates functional status ranging from "moderately severe disability" (unable to walk or to attend to own bodily needs without assistance)through to death. CV death includes death due to hemorrhage and death with undetermined/unknown cause. Diagnosis of myocardial infarction requires combination of: 1) evidence of myocardial necrosis either changes in cardiac biomarkers or post-mortem pathological findings); 2) supporting information derived from clinical presentation, electrocardiographic changes, or results of myocardial or coronary artery imaging.
| event/100 participant-years | Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Stroke | 5.11 (4.37 to 5.93) | 4.71 (4.01 to 5.51) |
| Ischemic stroke | 4.71 (4.01 to 5.51) | 4.56 (3.87 to 5.34) |
| Disabling stroke | 1.20 (0.86 to 1.62) | 0.84 (0.56 to 1.21) |
| CV death(includes death due to hemorrhage) | 0.99 (0.68 to 1.38) | 0.66 (0.42 to 1.00) |
| Myocardial infarction | 0.49 (0.29 to 0.79) | 0.67 (0.42 to 1.00) |
Life-threatening bleeding was defined as a subset of major bleeding that met at least one of the following criteria: 1) fatal bleeding; 2) symptomatic intracranial haemorrhage; 3) reduction in hemoglobin of at least 5 g/dl (50 g/l; 3.10 mmol/L); 4) transfusion of at least 4 units of packed red cells or whole blood; 5) associated with hypotension requiring the use of intravenous inotropic agents; 6) necessitated surgical intervention. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred.
| event/100 participant-years | Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Incidence Rate of Life-Threatening Bleeding Events | 1.02 (0.71 to 1.42) | 0.43 (0.24 to 0.72) |
Non-major clinically relevant bleeding was defined as non-major overt bleeding but required medical attention (example: hospitalization, medical treatment for bleeding), and/or was associated with the study drug interruption of more than 14 days. The results were based on the outcome events at or after randomization until the efficacy cut-off date. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred.
| event/100 participant-years | Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Incidence Rate of Clinically Relevant Non-Major Bleeding Events | 3.52 (2.91 to 4.21) | 2.32 (1.84 to 2.90) |
Intracranial hemorrhage included all bleeding events that occurred in intracerebral, sub arachnoidal as well as subdural or epidural sites. The below table displays results for all randomized participants and the outcomes at or after randomization until the efficacy cut-off date. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred.
| event/100 participant-years | Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Incidence Rate of Intracranial Hemorrhage | 0.70 (0.45 to 1.04) | 0.35 (0.18 to 0.61) |
Collected over From start of study drug administration until 2 days after the last dose of study drug, an average of 279 days. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Rivaroxaban 15 mg OD | 73/3,562 (2%) | 466/3,562 (13.1%) | 308/3,562 (8.6%) |
| Acetylsalicylic Acid 100 mg OD | 58/3,559 (1.6%) | 434/3,559 (12.2%) | 294/3,559 (8.3%) |
| Event | Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Atrial fibrillationCardiac disorders | 36/3562 | 37/3559 |
| PneumoniaInfections and infestations | 14/3562 | 14/3559 |
| OsteoarthritisMusculoskeletal and connective tissue disorders | 11/3562 | 3/3559 |
| SyncopeNervous system disorders | 10/3562 | 8/3559 |
| SeizureNervous system disorders | 9/3562 | 9/3559 |
| CataractEye disorders | 4/3562 | 8/3559 |
| Prostate cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/3562 | 8/3559 |
| EpilepsyNervous system disorders | 7/3562 | 8/3559 |
| Pulmonary embolismRespiratory, thoracic and mediastinal disorders | 1/3562 | 8/3559 |
| AnaemiaBlood and lymphatic system disorders | 8/3562 | 3/3559 |
| Event | Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Atrial fibrillationCardiac disorders | 60/3562 | 60/3559 |
| HypertensionVascular disorders | 11/3562 | 7/3559 |
| Medication errorInjury, poisoning and procedural complications | 10/3562 | 9/3559 |
| HeadacheNervous system disorders | 10/3562 | 8/3559 |
| DiarrhoeaGastrointestinal disorders | 8/3562 | 3/3559 |
| Abdominal pain upperGastrointestinal disorders | 5/3562 | 7/3559 |
| DizzinessNervous system disorders | 5/3562 | 7/3559 |
| Incorrect dose administeredInjury, poisoning and procedural complications | 6/3562 | 4/3559 |
| Treatment noncomplianceSocial circumstances | 2/3562 | 5/3559 |
| NauseaGastrointestinal disorders | 5/3562 | 1/3559 |
Intention-to-treat analysis set included all randomized participants.
| Age, Continuous(years) | Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD | Total |
|---|---|---|---|
| Mean | 66.9 ± 9.8 | 66.9 ± 9.8 | 66.9 ± 9.8 |
| Sex: Female, Male(Participants) | Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD | Total |
|---|---|---|---|
| Female | 1377 | 1400 | 2777 |
| Male | 2232 | 2204 | 4436 |
| Race (NIH/OMB)(Participants) | Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 716 | 698 | 1414 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 51 | 60 | 111 |
| White | 2613 | 2605 | 5218 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 229 | 241 | 470 |
| Stroke or TIA (prior to qualifying stroke) or Other medical history(count of participants) | Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD | Total |
|---|---|---|---|
| Stroke or TIA | 620 | 643 | 1263 |
| Other medical history | 2989 | 2961 | 5950 |
| Time from qualifying stroke to randomization(days) | Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD | Total |
|---|---|---|---|
| Median | 38.0 (15.0 to 89.0) | 36.0 (14.0 to 86.5) | 37.0 (14.0 to 88.0) |
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Studies of the drug tested here: Rivaroxaban