Efficacy and Safety of Rivaroxaban for the Prevention of Stroke in Subjects With Non-Valvular Atrial Fibrillation

Atrial Fibrillation Clinical Trial

Official title:

Evaluation of the Efficacy and Safety of Rivaroxaban (BAY59-7939) for the Prevention of Stroke and Non-central Nervous System Systemic Embolism in Subjects With Non-valvular Atrial Fibrillation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00494871
• Other study ID #: 12620
• Status: Completed
• Phase: Phase 3
• First received: June 29, 2007
• Last updated: April 1, 2015
• Start date: June 2007
• Est. completion date: January 2010

Study information

• Verified date: April 2015
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial Summary

This is a clinical study evaluating the efficacy and safety of rivaroxaban for stroke prevention in patients with atrial fibrillation (originally described in Japanese).

Description:

Within the US 'Johnson & Johnson Pharmaceutical Research & Development, L.L.C.' is sponsor.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1280
• Est. completion date: January 2010
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• 20 years or older

• Japanese male or female

• Non- valvular atrial fibrillation documented by ECG

• Patients with a risk of stroke and non-CNS systemic embolism

Exclusion Criteria:

• Significant mitral stenosis

• Patients in whom anticoagulants are contraindicated

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Drug:
• Rivaroxaban (Xarelto, BAY59-7939)
Participants orally administered rivaroxaban 15 mg OD (CrCL [creatinine clearance] >= 50 mL/min) or 10 mg OD (CrCL 30-49 mL/min)
• Warfarin
Participants orally administered a warfarin potassium tablet (INR [international normalized ratio] target was 1.6-2.6 for patients >70 years and 2.0-3.0 for patients <70 years)
• Rivaroxaban placebo
Participants orally administered a rivaroxaban placebo tablet
• Warfarin placebo
Participants orally administered a warfarin placebo tablet (adjusted based upon sham INR values)

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Bayer	Janssen R&D, L.L.C.

Country where clinical trial is conducted

Japan, 

References & Publications (11)

Chan MY, Lin M, Lucas J, Moseley A, Thompson JW, Cyr D, Ueda H, Kajikawa M, Ortel TL, Becker RC. Plasma proteomics of patients with non-valvular atrial fibrillation on chronic anti-coagulation with warfarin or a direct factor Xa inhibitor. Thromb Haemost. — View Citation

Hori M, Kajikawa M. The J-ROCKET AF Study: a matter of ethnicity or a matter of weight? Reply. Circ J. 2013;77(10):2637. Epub 2013 Aug 1. — View Citation

Hori M, Matsumoto M, Tanahashi N, Momomura S, Uchiyama S, Goto S, Izumi T, Koretsune Y, Kajikawa M, Kato M, Ueda H, Iekushi K, Yamanaka S, Tajiri M; J-ROCKET AF Study Investigators. Rivaroxaban versus warfarin in Japanese patients with nonvalvular atrial — View Citation

Hori M, Matsumoto M, Tanahashi N, Momomura S, Uchiyama S, Goto S, Izumi T, Koretsune Y, Kajikawa M, Kato M, Ueda H, Iekushi K, Yamanaka S, Tajiri M; J-ROCKET AF Study Investigators. Rivaroxaban vs. warfarin in Japanese patients with non-valvular atrial fi — View Citation

Hori M, Matsumoto M, Tanahashi N, Momomura S, Uchiyama S, Goto S, Izumi T, Koretsune Y, Kajikawa M, Kato M, Ueda H, Iwamoto K, Tajiri M; J-ROCKET AF study investigators. Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation – the J-ROCKET — View Citation

Hori M, Matsumoto M, Tanahashi N, Momomura S, Uchiyama S, Goto S, Izumi T, Koretsune Y, Kajikawa M, Kato M, Ueda H, Iwamoto K, Tajiri M; J-ROCKET AF study investigators. Safety and efficacy of adjusted dose of rivaroxaban in Japanese patients with non-val — View Citation

Kaneko M, Tanigawa T, Hashizume K, Kajikawa M, Tajiri M, Mueck W. Confirmation of model-based dose selection for a Japanese phase III study of rivaroxaban in non-valvular atrial fibrillation patients. Drug Metab Pharmacokinet. 2013;28(4):321-31. Epub 2013 — View Citation

Matsumoto M, Hori M, Tanahashi N, Momomura S, Uchiyama S, Goto S, Izumi T, Koretsune Y, Kajikawa M, Kato M, Ueda H, Iekushi K, Yamanaka S, Tajiri M; J-ROCKET AF Study Investigators. Rivaroxaban versus warfarin in Japanese patients with non-valvular atrial — View Citation

Tanahashi N, Hori M, Matsumoto M, Momomura S, Uchiyama S, Goto S, Izumi T, Koretsune Y, Kajikawa M, Kato M, Ueda H, Iwamoto K, Tajiri M; J-ROCKET AF Study Investigators. Rivaroxaban versus warfarin in Japanese patients with nonvalvular atrial fibrillation — View Citation

Tanigawa T, Kaneko M, Hashizume K, Kajikawa M, Ueda H, Tajiri M, Paolini JF, Mueck W. Model-based dose selection for phase III rivaroxaban study in Japanese patients with non-valvular atrial fibrillation. Drug Metab Pharmacokinet. 2013;28(1):59-70. Epub 2 — View Citation

Uchiyama S, Hori M, Matsumoto M, Tanahashi N, Momomura S, Goto S, Izumi T, Koretsune Y, Kajikawa M, Kato M, Ueda H, Iekushi K, Yamanaka S, Tajiri M; J-ROCKET AF Study Investigators. Net clinical benefit of rivaroxaban versus warfarin in Japanese patients — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event Rate of the Composite Endpoint of Adjudicated Major Bleeding or Adjudicated Non-major Clinically Relevant Bleeding	Major bleeding: clinically overt bleeding (COB) associated with a fall in hemoglobin =2 g/dL, leading to transfusion =2 units of packed red blood cells or whole blood, occurring in a critical site or contributing to death. Non-major clinically relevant bleeding: COB that does not meet the definition of major bleeding, but requires medical intervention or unscheduled contact with the physician, (temporary) discontinuation of the study treatment, discomfort to the subject such as pain, or impairment of activities of daily life.	Up to 2 days after the last dose	Yes
Secondary	Event Rate of the Composite Endpoint of Adjudicated Stroke and Non-central Nervous System (CNS) Systemic Embolism	This is the principal efficacy endpoint. Stroke included hemorrhagic, ischemic infarction and unknown. Arterial emboli in the following areas were "non-CNS systemic embolism": peripheral arterial in the upper and lower extremities, renal, mesenteric, splenic, hepatic, ocular/retinal and others. Pulmonary embolism or myocardial infarction was excluded.	Up to 2 days after the last dose	No
Secondary	Event Rate of the Composite Endpoint of Adjudicated Stroke, Non-CNS Systemic Embolism, and Vascular Death	Stroke included hemorrhagic, ischemic infarction and unknown. Arterial emboli in the following areas were "non-CNS systemic embolism": peripheral arterial in the upper and lower extremities, renal, mesenteric, splenic, hepatic, ocular/retinal and others. Pulmonary embolism or myocardial infarction was excluded. Any death that was not clearly non-vascular.	Up to 2 days after the last dose	No
Secondary	Event Rate of the Composite Endpoint of Adjudicated Stroke, Non-CNS Systemic Embolism, Myocardial Infarction, and Vascular Death	Stroke included hemorrhagic, ischemic infarction and unknown. Arterial emboli in the following areas were "non-CNS systemic embolism": peripheral arterial in the upper and lower extremities, renal, mesenteric, splenic, hepatic, ocular/retinal and others. Pulmonary embolism or myocardial infarction was excluded. Myocardial infarction: assessed based on either cardiac biomarkers, new abnormal Q waves appeared on electrocardiogram for =2 leads, or autopsy confirmation. Any death that was not clearly non-vascular.	Up to 2 days after the last dose	No
Secondary	Event Rate of Stroke	All events were adjudicated and confirmed by a central independent committee blinded to treatment. Stroke included hemorrhagic (Stroke with local collections of intraparenchymal blood. Subarachnoid hemorrhage, subdural hemorrhage, and epidural hemorrhage were excluded.), ischemic infarction (Stroke without focal collection of intracranial blood) and unknown (No imaging data and anatomic findings were available.).	Up to 2 days after the last dose	No
Secondary	Event Rate of Non-CNS Systemic Embolism	All events were adjudicated and confirmed by a central independent committee blinded to treatment. Non-CNS systemic embolism was abrupt vascular insufficiency associated with clinical or radiological evidence of arterial occlusion in the absence of other likely mechanisms (such as trauma, atherosclerosis, and instrumentation). Arterial emboli in the following areas were "non-CNS systemic embolism": peripheral arterial in the upper and lower extremities, renal, mesenteric, splenic, hepatic, ocular/retinal and others. Pulmonary embolism or myocardial infarction was excluded from this category.	Up to 2 days after the last dose	No
Secondary	Event Rate of Myocardial Infarction	All events were adjudicated and confirmed by a central independent committee blinded to treatment. Myocardial infarction was assessed based on either cardiac bio-markers (troponin I, troponin T, or creatine kinase-muscle and brain subunit isozyme), new abnormal Q waves appeared on ECG for 2 or more leads, or autopsy confirmation.	Up to 2 days after the last dose	No
Secondary	Event Rate of Vascular Death	All events were adjudicated and confirmed by a central independent committee blinded to treatment. Any death that was not clearly non-vascular (e.g., deaths due to spontaneous bleeding, myocardial infarction, stroke, cardiac failure, and arrhythmia)	Up to 2 days after the last dose	No
Secondary	Event Rate of Stroke With Serious Residual Disability	All events were adjudicated and confirmed by a central independent committee blinded to treatment. A stroke was considered disabling if the participant's modified Rankin score was between 3 and 5, inclusive.	Up to 2 days after the last dose	No
Secondary	Event Rate of All-cause Death	All events were adjudicated and confirmed by a central independent committee blinded to treatment. All-cause death included vascular death and non-vascular death.	Up to 2 days after the last dose	No
Secondary	Event Rate of Adjudicated Major Bleeding	All events were adjudicated and confirmed by a central independent committee blinded to treatment. Major bleeding was clinically overt bleeding associated with a fall in hemoglobin of 2 g/dL or higher, 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.	Up to 2 days after the last dose	Yes
Secondary	Event Rate Adjudicated Non-major Clinically Relevant Bleeding	All events were adjudicated and confirmed by a central independent committee blinded to treatment. Non-major clinically relevant bleeding was clinically overt bleeding that does not meet the definition of major bleeding, but requires medical intervention or unscheduled contact with the physician, (temporary) discontinuation of the study treatment, discomfort to the subject such as pain, or impairment of activities of daily life.	Up to 2 days after the last dose	Yes

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