Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication XARELTO is a factor Xa inhibitor indicated: to reduce risk of stroke and systemic embolism in nonvalvular atrial fibrillation ( 1.1 ) for treatment of deep vein thrombosis (DVT) ( 1.2 ) for treatment of pulmonary embolism (PE) ( 1.3 ) for reduction in the risk of recurrence of DVT or PE ( 1.4 ) for the prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery ( 1.5 ) for… FDA label
Also known as Rivaroxaban (normal renal function), JNJ-39039039, Bay 59-7939, Xarelto
Rivaroxaban · 20 trials · 27 indications
Non-ICH major hemorrhage is derived from the International Society on Thrombosis and Haemostasis (ISTH) criteria consisting of any of the following: * Fatal bleeding * Symptomatic bleeding in a critical area or organ, such as subarachnoid, intraventricular, subdural, epidural, spinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome * Symptomatic bleeding causing a fall in hemoglobin level of 1.24 mmol/L (20g/L or greater) or more, or leading to transfusion of two units or more of whole blood or red cells
The definition of ischemic stroke is the American Heart Association definition that includes acute focal signs or symptoms of cerebral, spinal cord, or retinal involvement of any duration associated with imaging, pathological, or other objective evidence of arterial infarction OR clinical evidence of cerebral, spinal cord, or retinal focal arterial ischemic injury based on symptoms persisting greater than or equal to 24 hours.
Thrombotic event was defined as the appearance of a new thrombotic burden within the cardiovascular system on either routine surveillance or clinically indicated imaging, or the occurrence of a clinical event known to be strongly associated with thrombus (such as cardioembolic stroke, pulmonary embolism). The event included ischemic stroke, pulmonary embolism, venous thrombosis, arterial/intracardiac thrombosis, and other thrombosis.
Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Bleeding events were categorized into major, clinically relevant non-major bleeding (CRNM), and trivial bleeding events. Major bleeding: overt bleeding and associated with a fall in hemoglobin of 2 gram per deciliter (g/dL) or more; or leading to a transfusion of the equivalent of 2 or more units of packed red blood cells or whole blood in adults; or occurring in a critical site: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal; or contributing to death. CRNM bleeding: overt bleeding not meeting the criteria for major bleeding but associated with: Medical intervention, or Unscheduled contact with a physician, cessation of study treatment, or Discomfort for the subject such as pain, or Impairment of activities of daily life. Trivial bleeding: any other overt bleeding event that does not meet criteria for CRNM bleeding.
Absolute prothrombin time was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Absolute PT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Absolute PT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average the participants included in the given time-range is presented here.
Absolute PT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Absolute PT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Absolute PT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Absolute PT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Absolute PT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Absolute PT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and average of the participants included in the given time-range is presented here.
aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average the participants included in the given time-range is presented here.
aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average for the participants included in the given time-range is presented here.
aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Anti-FXa was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Anti-FXa was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Anti-FXa was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Anti-FXa was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Anti-FXa was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Anti-FXa was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.
Percentage of participants with time to the first occurrence of primary efficacy endpoint (composite and components) was reported. The primary efficacy composite endpoint is time to first occurrence of objectively confirmed symptomatic and asymptomatic lower extremity proximal DVT, symptomatic lower extremity distal DVT, symptomatic upper extremity DVT, symptomatic non-fatal PE, incidental PE, or VTE-related death as adjudicated by an independent blinded Clinical Endpoint Committee (CEC).
Major bleeding is defined as clinically overt bleeding that is associated with a reduction in hemoglobin of 2 gram per deciliter (g/dL) or more, or a transfusion of 2 or more units of packed red blood cells or whole blood, or occurrence at a critical site defined as intracranial, intra-spinal, intraocular, pericardial, intra-articular, intra-muscular with compartment syndrome, retroperitoneal, or fatal outcome.
Symptomatic VTE included lower extremity deep vein thrombosis (DVT) and non-fatal pulmonary embolism (PE). Event rate was defined as number of events per 100 participants in 45 days of follow up. Participants who did not have events were censored on the minimum of last visit before or on death, or Day 45.
A major bleeding event was defined using validated International Society on Thrombosis and Haemostasis (ISTH) bleeding criteria. A major bleeding event was defined as overt bleeding that was associated with a fall in hemoglobin of 2 gram per deciliter (g/dL) or more, or a transfusion of 2 or more units of packed red blood cells or whole blood, or a critical site defined as intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal, or a fatal outcome. Event rate was defined as number of events per 100 participants in 45 days of follow up. Participants who did not have events were censored on the minimum of last visit before or on death, or last dose + 2 days.
Event Rate of all-cause mortality (ACM), MI, or stroke were assessed. Event rate estimated based on the time to the first occurrence of the event were reported in the study. Event Rate / (100 patient \[pt\]-year \[yr\]) = 100\*n/(total risk exposure), where n is the number of events.
Event rate of either fatal bleeding or bleeding into critical space with potential for permanent disability were assessed. Fatal bleeding event was death within 7 days after a bleeding event which required hospitalization or met International Society on Thrombosis and Haemostasis(ISTH) major bleeding definition criteria. Fatal bleeding events included those met criteria in 3 categories: 1: Any ISTH major bleeding event consider primary cause of death by investigator; 2: Any ISTH major bleeding event not considered to be primary cause of death by investigator but resulted in death within 7 days;3: Any bleeding event resulted in hospital stay and death within 7 days. Bleeding into critical space with potential for permanent disability included 7 critical spaces: intracranial, intraspinal, intraocular. Event rate estimated based on time to first occurrence of event were reported in the study. Event Rate / (100 pt-yr) = 100\*n/(total risk exposure), where n is the number of events.
Clinically significant bleeding is a composite of Thrombolysis in Myocardial Infarction (TIMI) major bleeding, minor bleeding, and bleeding requiring medical attention (BRMA). TIMI major bleeding is defined as any symptomatic intracranial hemorrhage, clinically overt signs of hemorrhage (including imaging) associated with a drop in hemoglobin of greater than or equal to (\>=) 5 grams per deciliter (g/dL) (or when the hemoglobin concentration is not available, an absolute drop in hematocrit of \>=15 percent (%)). TIMI minor bleeding event is defined as any clinically overt sign of hemorrhage (including imaging) that is associated with a fall in hemoglobin concentration of 3 to less than (\<) 5 g/dL (or, when hemoglobin concentration is not available, a fall in hematocrit of 9 percent to \<15 percent). A BRMA event is defined as any bleeding event that requires medical treatment, surgical treatment, or laboratory evaluation, and does not meet criteria for a major or minor bleeding event.
Post-procedure major bleeding events include Thrombolysis in Myocardial Infarction (TIMI), International Society on Thrombosis and Haemostasis (ISTH) and Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) Severe/life threatening bleeding.
Descriptive statistics for per-patient maximum Anti-Factor Xa laboratory value selected from the 7 consecutive blood draws (0, 2, 4, 6, 8, 12 and 24 hrs post dose) on Day 1 and Day 3
Descriptive statistics for per-patient maximum prothrombin time laboratory value selected from the 7 consecutive blood draws (0, 2, 4, 6, 8, 12 and 24 hrs post dose) on Day 1 and Day 3
The percentage of patients with the first occurrence of the composite of death, myocardial infarction, or stroke. The statistical analysis was based on the time from randomization to the first occurrence of the event while on treatment.
A composite endpoint of: asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and VTE-related death.
A composite endpoint of: asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and VTE-related death.
All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for fatal PE) or unexplained death for which DVT/PE could not be ruled out (for fatal PE), and/or case summaries.
The number of patients with the first occurrence of a stroke or non-CNS systemic embolism while on treatment (defined as the time interval from the first dose to the last dose of study drug plus 2 days). The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.
The number of patients with the first occurrence of a stroke or non-CNS systemic embolism while on treatment (defined as the time interval from the first dose to the last dose of study drug plus 2 days). The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.
The number of patients with the first occurrence of a major or non-major clinically relevant bleeding event while on treatment. The statistical analysis is based on time from the first dose of study drug to the first occurrence of the event while on treatment.
Non CABG-related TIMI clinically significant bleeding events are sum of non CABG-related TIMI major bleeding events, TIMI minor bleeding events and TIMI bleeding events requiring medical attention. Major: any symptomatic intracranial bleeding: clinically overt signs of hemorrhage with hemoglobin (Hb) drop of greater than or equal to (\>=)5 gram per deciliter (g/dl) (or absolute drop in hematocrit of \>=15%) and fatal bleeding (results in death within 7 days); Minor: clinically overt sign of hemorrhage with Hb drop of 3 - \<5 g/dl (or drop in hematocrit of 9 - \<15%); requiring medical attention: bleeding event that required medical, surgical treatment/laboratory evaluation and did not meet criteria for major/minor bleeding event.
Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade. The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II. The initial read-out is in seconds. Mean and standard deviation (SD) values are presented for PT baseline.
Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade. The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II. The initial read-out of PT is in seconds. The PT slope describes the linear increase of PT for one unit increase in concentration, thus the unit of PT slope is s\*(µg/L)\^-1. The final population PK/PD model included a fixed slope that was fitted to the data of the 19 patients that were eligible for evaluation. The estimated mean value (fixed/ the same for all patients in this study) is presented for PT slope.
AUC(0-24)ss was predicted from rivaroxaban plasma concentrations for each individual participant and was only considered for the time period during which participants concomitantly received rivaroxaban and a strong cytochrome P450 isoenzyme 3A4 (CYP3A4) inducer.
Cmax,ss was predicted from rivaroxaban plasma concentrations for each individual participant and was only considered for the time period during which participants concomitantly received rivaroxaban and a strong CYP3A4 inducer.
Cmin,ss was predicted for each individual participant from rivaroxaban plasma concentrations and was only considered for the time period during which participants concomitantly received rivaroxaban and a strong CYP3A4 inducer.
All events were adjudicated and confirmed by a central independent adjudication committee. Clinically relevant bleeding included major bleeding (overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of 2 or more units of packed red blood cells or whole blood, occurring in a critical site or contributing to death) and non-major bleeding associated with medical intervention, unscheduled physician contact, (temporary) cessation of study treatment, discomfort for the participants such as pain, or impairment of activities of daily life.
The number of patients with a first occurrence of a TIMI clinically significant bleeding event that occurred from the time of randomization to the time of the last patient contact. TIMI clinically significant bleeding events included TIMI minor bleeding events, TIMI major bleeding events, or any bleeding that required medical attention.
The number of patients who died due to any cause or had a first occurrence of MI (including repeat MI) or stroke (ischemic, hemorrhagic or unknown) or severe recurrent ischemia requiring revascularization from the time of randomization to the last date of patient contact.
The Cmax is the maximum observed plasma concentration.
The AUClast is the area under the plasma concentration-time curve from time zero to time of last quantifiable concentration.
The AUCinfinity is the area under the plasma concentration-time curve from time zero to extrapolated infinite time, calculated as the sum of AUClast and Clast/lambda(z), where AUClast is area under the plasma concentration-time curve from time zero to time of last quantifiable plasma concentration; Clast is the last observed quantifiable concentration; and lambda(z) is first-order rate constant associated with the terminal portion of the semilogarithmic drug concentration-time curve.
The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample (AUC is defined as area under the concentration vs. time curve from zero to infinity after single (first) dose).
The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample; \[AUC (0-tn)\] is defined as AUC from time 0 to the last data point above the Lower Limit of Quantification.
Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade. The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II. The initial read-out is in seconds. Higher values than the baseline indicate anticoagulant effects. Emax on PT was measured as the ratio of maximum PT (measured in seconds) divided by PT (measured in seconds) at baseline.
Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade. The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II. The initial read-out is in seconds. Higher values than the baseline indicate anticoagulant effects. Emax,BA on PT was measured as maximum PT (measured in seconds) minus PT (measured in seconds) at baseline.
| Arm | Type | Description |
|---|---|---|
| Experimental Arm: Ticagrelor and Aspirin | EXPERIMENTAL | Ticagrelor (180mg loading dose, then 90mg twice daily) and aspirin (81mg daily) |
| Standard of Care Arm: Clopidogrel and Aspirin | ACTIVE_COMPARATOR | Clopidogrel (600mg loading dose, then 75mg once daily) and aspirin (81mg daily) |
| Experimental Arm: Rivaroxaban and Aspirin | EXPERIMENTAL | Rivaroxaban (2.5mg twice daily) and aspirin (81mg daily) |
| Rivaroxaban | EXPERIMENTAL | - |
| Acetylsalicylic Acid | EXPERIMENTAL | - |
| Placebo | EXPERIMENTAL | Participants will be administered matching placebo tablet orally once daily for 180 days. |
| Rivaroxaban 2.5 mg | EXPERIMENTAL | Each participant will receive 2.5 mg of rivaroxaban twice daily with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician). |
| rivaroxaban 2.5 mg twice daily | EXPERIMENTAL | rivaroxaban 2.5 mg tablet twice daily plus low-dose aspirin (ASA) 75 to 100 mg once daily and clopidogrel 75 mg tablet once daily (or prasugrel 10 mg tablet once daily or ticagrelor 90 mg tablet twice daily) followed by rivaroxaban 15 mg tablet (or 10 mg for subjects with moderate renal impairment) once daily plus low-dose ASA for 12 months |
| vitamin K antagonist (VKA) | EXPERIMENTAL | dose-adjusted vitamin K antagonist (VKA) once daily (target International Normalized Ratio (INR) 2.0 to 3.0) plus low-dose ASA, 75 to 100 mg per day, and clopidogrel 75 mg once daily (or prasugrel 10 mg tablet once daily or ticagrelor 90 mg tablet twice daily) followed by dose-adjusted VKA once daily (target INR 2.0 to 3.0 or 2.0 to 2.5 at the investigator discretion) plus low-dose ASA for 12 months |
| rivaroxaban 15 mg once daily | EXPERIMENTAL | rivaroxaban 15 mg (or 10 mg for subjects with moderate renal impairment) once daily plus clopidogrel 75 mg tablet once daily (or prasugrel 10 mg tablet once daily or ticagrelor 90 mg tablet twice daily) for 12 months |
| 001 | EXPERIMENTAL | Rivaroxaban 10mg tablet daily receiving the first dose within two days after admission to the subacute unit. The total duration of combined venous blood clot prevention therapy with enoxaparin and rivaroxaban may not exceed 35 days for patients with total hip replacement or 14 days with total knee replacement |
| Rivaroxaban 2.5 mg bid | EXPERIMENTAL | One 2.5 mg rivaroxaban tablet twice daily for up to 6 months |
| Rivaroxaban 5 mg bid | EXPERIMENTAL | One 5 mg rivaroxaban tablet twice daily for up to 6 months |
| Rivaroxaban (Xarelto, BAY59-7939) | EXPERIMENTAL | Participants received 10 mg oral rivaroxaban tablet once daily (OD) for 35 +/- 4 days, plus subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days |
| Enoxaparin | ACTIVE_COMPARATOR | Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days |
| Enoxaparin/VKA | ACTIVE_COMPARATOR | Participants were to receive 1.0 mg/kg enoxaparin twice daily (subcutaneous) for at least 5 days, plus vitamin K antagonist (VKA) (oral) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 to 3.0) |
| Warfarin | ACTIVE_COMPARATOR | - |
| Stratum 1/ASA | ACTIVE_COMPARATOR | Acetylsalicylic acid (ASA) 100 milligram (mg) enteric-coated tablet once daily orally along with clopidogrel 75 mg once daily orally, up to either 180 days after randomization of the last enrolled participant in the study or Day 360, whichever occurs earlier. |
| Stratum 1/Rivaroxaban | EXPERIMENTAL | Rivaroxaban 2.5 mg tablet twice daily orally along with clopidogrel 75 mg once daily orally, up to either 180 days after randomization of the last enrolled participant in the study or Day 360, whichever occurs earlier. |
| Stratum 2/ASA | ACTIVE_COMPARATOR | ASA 100 mg enteric-coated tablet once daily orally along with ticagrelor 90 mg twice daily orally, up to either 180 days after randomization of the last enrolled participant in the study or Day 360, whichever occurs earlier. |
| Stratum 2/Rivaroxaban | EXPERIMENTAL | Rivaroxaban 2.5 mg tablet twice daily orally along with ticagrelor 90 mg twice daily orally, up to either 180 days after randomization of the last enrolled participant in the study or Day 360, whichever occurs earlier. |
| 002 | EXPERIMENTAL | Rivaroxaban/Placebo 1 rivaroxaban tablet once daily (and 1 placebo tablet once daily) for 6 months. Safety at each dose level will be confirmed before additional patients are randomized to the next higher dose level. |
| 003 | PLACEBO_COMPARATOR | Placebo 1 placebo tablet twice daily for 6 months. |
| Group A | EXPERIMENTAL | Participants with end-stage renal disease (ESRD), will receive a single 15-milligram (mg) oral dose of rivaroxaban in Treatment Period 1 on Day 1, administered 2 hours before the start of a 4-hour hemodialysis session followed 7 to 14 days later by Treatment Period 2 wherein a single 15-mg oral dose of rivaroxaban will be given 3 hours after the completion of a 4-hour hemodialysis session on Day 1. |
| Group B | EXPERIMENTAL | Healthy control participants matching to 'Group A' participants, will receive a single 15-mg oral dose of rivaroxaban on Day 1. |
| Rivaroxaban (Xarelto, BAY59-7939) first 2*5 mg, then 1*10 mg | EXPERIMENTAL | Single oral dose of rivaroxaban administered under fasting conditions 2\*5 mg tablet in first intervention period and 1\*10 mg tablet in second intervention period (after washout period) |
| Rivaroxaban (Xarelto, BAY59-7939) first 1*10 mg, then 2*5 mg | EXPERIMENTAL | Single oral dose of rivaroxaban administered under fasting conditions 1\*10 mg tablet in first intervention period and 2\*5 mg tablet in second intervention period (after washout period) |
| Warfarin followed by Rivaroxaban (Xarelto, BAY59-7939) | EXPERIMENTAL | Days -6 and -5: 10 mg warfarin once daily or lower depending on international normalized ratio (INR); Days -4 to -1 (could be prolonged by two days): 2.5, 5, 10, 12.5 or 15 mg warfarin once daily depending on INR; Days 0 to 3: 20 mg rivaroxaban once daily; Day 5: 10 mg vitamin K once daily |
| Warfarin followed by Placebo | PLACEBO_COMPARATOR | Days -6 and -5: 10 mg warfarin once daily or lower depending on INR; Days -4 to -1 (could be prolonged by two days): 2.5, 5, 10, 12.5 or 15 mg warfarin once daily depending on INR; Days 0 to 3: 1 tablet matching placebo once daily; Day 5: 10 mg vitamin K once daily |
| Name | Type | Description |
|---|---|---|
| Ticagrelor + Aspirin | DRUG | ticagrelor (180 mg loading dose, then 90mg twice daily) and aspirin (81mg daily) |
| Rivaroxaban + Aspirin | DRUG | low dose rivaroxaban (2.5mg twice daily) and aspirin (81mg daily) |
| Clopidogrel + Aspirin | DRUG | clopidogrel (600mg loading dose, then 75mg daily) and aspirin (81mg daily) |
| Risk Factor Management | OTHER | Risk factors for stroke (LDL, blood pressure, non-HDL cholesterol, diabetes, smoking, weight, and physical activity) will be monitored and managed. |
| Rivaroxaban | DRUG | Participants will receive oral suspension containing rivaroxaban 1 milligram per milliliter (mg/ml) twice daily in Part A and Part B. Following total daily doses of Rivaroxaban will be administered based on the weight of the participants: 7 to \<8 kilogram (kg) will receive 2.2 milligram (mg); 8 to \<10 kg will receive 3.2 mg; 10 to\<12 kg will receive 3.4 mg; 12 to \<20 will receive 4.0 mg and 20 to \<30 will receive 5.0 mg. |
| Acetylsalicylic Acid | DRUG | Participants will receive 5 milligram per kilogram (mg/kg) of acetylsalicylic acid once daily up to 12 months in Part B. |
| Placebo | DRUG | Placebo tablet will be administered orally once daily for 180 days. |
| Rivaroxaban, 10 mg | DRUG | Patients, randomly allocated to the rivaroxaban arm, with a creatinine clearance at screening greater than or equal to (\>=)50 mL/min will receive 10 mg rivaroxaban tablet with or without food. |
| Rivaroxaban, 7.5 mg | DRUG | Patients, randomly allocated to the rivaroxaban arm, with a creatinine clearance at screening from \>=30 to less than (\<)50 mL/min will receive 7.5 mg rivaroxaban tablet with or without food. |
| Standard of care for heart failure and coronary artery disease | OTHER | Each participant's standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician) should be continued throughout the study. |
| rivaroxaban 2.5 mg | DRUG | One 2.5 mg tablet twice daily for up to twelve months |
| rivaroxaban 15 mg | DRUG | One 15 mg tablet once daily for up to twelve months |
| rivaroxaban 10 mg | DRUG | One 10 mg tablet once daily for up to twelve months |
| aspirin (ASA) | DRUG | Low-dose aspirin tablet once daily for twelve months |
| vitamin K antagonist (VKA) | DRUG | Dose-adjusted VKA tablet (target International Normalized Ratio (INR) 2.0 to 3.0) once daily for twelve months |
| clopidogrel | DRUG | One 75 mg tablet once daily for up to twelve months |
| prasugrel | DRUG | One 10 mg tablet once daily for up to twelve months |
| ticagrelor | DRUG | One 90 mg tablet twice daily for up to twelve months |
| uninterrupted vitamin K antagonist (VKA) | DRUG | dose-adjusted vitamin K antagonist (VKA) to achieve a recommended International Normalized Ratio (INR) of 2.0 to 3.0 |
| Rivaroxaban 5 mg | DRUG | One tablet twice daily |
| Standard of care | DRUG | - |
| Rivaroxaban (Xarelto, BAY59-7939) | DRUG | Oral rivaroxaban 10 mg once daily administered for 35 +/- 4 days |
| Enoxaparin | DRUG | Subcutaneous enoxaparin 40 mg once daily (OD) administered for 10 +/- 4 days |
| Rivaroxaban placebo | DRUG | Oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days |
| Enoxaparin placebo | DRUG | Subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days |
| Enoxaparin followed by VKA | DRUG | Enoxaparin 1.0 mg/kg twice daily with a minimal duration of 5 days. This 5 days treatment could include the period up to 36 h before randomization if enoxaparin twice-daily was used. VKA should be started as soon as possible but not later than 48 hours after randomization. |
| Enoxaparin overlapping with and followed by VKA | DRUG | Enoxaparin 1.0 mg/kg twice daily with a minimal duration of 5 days. This 5 days treatment could include the period up to 36 hr before randomization if enoxaparin twice-daily was used. VKA should be started as soon as possible but not later than 48 hours after randomization. |
| Warfarin | DRUG | Type=exact number, unit=mg, number=1, 2.5, or 5 mg, form=tablet, route=oral use. Number of warfarin tablets to be determined based on target INR values once daily for an expected maximum treatment period of up to 32 months that may extend up to 4 years |
| Matching placebo for Rivaroxaban arm (Warfarin placebo) | DRUG | Form=tablet, route=oral. One warfarin placebo tablet taken orally once daily for up to an expected maximum treatment period of 32 months that may extend up to 4 years |
| Matching placebo for Warfarin arm (Rivaroxaban placebo) | DRUG | Form-tablet, Route=oral administration. Number of rivaroxaban placebo determined by the number of warfarin tablets taken. Duration of treatment is up to an expected maximum treatment period of 32 months that may extend up to 4 years |
| Rivaroxaban/Placebo | DRUG | 1 rivaroxaban tablet once daily (and 1 placebo tablet once daily) for 6 months. Safety at each dose level will be confirmed before additional patients are randomized to the next higher dose level. |
| Warfarin (Coumadin) | DRUG | Days -6 and -5: 10 mg warfarin (Coumadin) once daily, dosage lower if the INR is already high on day -5; Days -4 to -1 (could be prolonged by two days): 2.5, 5, 10, 12.5 or 15 mg warfarin (Coumadin) once daily, dosage depending on INR |
| Vitamin K (Konakion) | DRUG | Day 5: 10 mg vitamin K (Konakion) once daily |
Inclusion Criteria: * Acute focal symptoms or signs of any duration associated with imaging, pathological, or other objective evidence of arterial infarction OR clinical evidence of cerebral, spinal cord, or retinal focal arterial ischemic injury based on symptoms persisting greater than or equal t...
Rivaroxaban is an oral anticoagulant studied across several cardiovascular and thrombotic conditions, including acute coronary syndrome, atrial fibrillation, heart failure, end-stage renal disease, intracranial arteriosclerosis, and arthritis. It is also being evaluated for thromboprophylaxis in pediatric patients after the Fontan procedure and in ambulatory cancer patients. It is a small molecule Factor Xa inhibitor.
Rivaroxaban targets coagulation factor Xa, also known as F10. It acts as an inhibitor of this enzyme, which plays a central role in the coagulation cascade. By inhibiting factor Xa, rivaroxaban reduces thrombin generation and clot formation. This mechanism underlies its use in conditions where anticoagulation is needed.
Rivaroxaban is developed by Johnson & Johnson, which trades under the ticker JNJ. The company is responsible for its clinical development and commercialization. Johnson & Johnson has sponsored multiple Phase 3 trials of rivaroxaban across cardiovascular and thrombotic indications.
Rivaroxaban is in Phase 3 clinical development. It is an investigational drug and has not been approved by the FDA for the indications currently under study. The Phase 3 program includes trials in intracranial arteriosclerosis, pediatric thromboprophylaxis after the Fontan procedure, and venous thromboembolism prophylaxis in ambulatory cancer patients.
Rivaroxaban has been studied in several clinical trials, including NCT05047172, a Phase 3 study comparing anticoagulation and antiplatelet therapies for intracranial vascular atherostenosis; NCT02846532, a Phase 3 pediatric thromboprophylaxis study after the Fontan procedure; and NCT02555878, a Phase 3 trial of venous thromboembolism prophylaxis in ambulatory cancer patients. A Phase 2 trial, NCT02293395, evaluated safety in acute coronary syndrome.
Yes, rivaroxaban is also known by the brand name Xarelto. It has been referred to by other names including BAY59-7939 and various dosage forms such as rivaroxaban 2.5 mg, 10 mg, and 15 mg. The combination of rivaroxaban plus aspirin is also studied. These names all refer to the same active ingredient.