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

This study has been completed.
Sponsor:
Collaborator:
Janssen R&D, L.L.C.
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00494871
First received: June 29, 2007
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

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


Condition Intervention Phase
Atrial Fibrillation
Drug: Rivaroxaban (Xarelto, BAY59-7939)
Drug: Warfarin
Drug: Rivaroxaban placebo
Drug: Warfarin placebo
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Event Rate of the Composite Endpoint of Adjudicated Major Bleeding or Adjudicated Non-major Clinically Relevant Bleeding [ Time Frame: Up to 2 days after the last dose ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Event Rate of the Composite Endpoint of Adjudicated Stroke and Non-central Nervous System (CNS) Systemic Embolism [ Time Frame: Up to 2 days after the last dose ] [ Designated as safety issue: No ]
    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.

  • Event Rate of the Composite Endpoint of Adjudicated Stroke, Non-CNS Systemic Embolism, and Vascular Death [ Time Frame: Up to 2 days after the last dose ] [ Designated as safety issue: No ]
    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.

  • Event Rate of the Composite Endpoint of Adjudicated Stroke, Non-CNS Systemic Embolism, Myocardial Infarction, and Vascular Death [ Time Frame: Up to 2 days after the last dose ] [ Designated as safety issue: No ]
    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.

  • Event Rate of Stroke [ Time Frame: Up to 2 days after the last dose ] [ Designated as safety issue: No ]
    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.).

  • Event Rate of Non-CNS Systemic Embolism [ Time Frame: Up to 2 days after the last dose ] [ Designated as safety issue: No ]
    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.

  • Event Rate of Myocardial Infarction [ Time Frame: Up to 2 days after the last dose ] [ Designated as safety issue: No ]
    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.

  • Event Rate of Vascular Death [ Time Frame: Up to 2 days after the last dose ] [ Designated as safety issue: No ]
    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)

  • Event Rate of Stroke With Serious Residual Disability [ Time Frame: Up to 2 days after the last dose ] [ Designated as safety issue: No ]
    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.

  • Event Rate of All-cause Death [ Time Frame: Up to 2 days after the last dose ] [ Designated as safety issue: No ]
    All events were adjudicated and confirmed by a central independent committee blinded to treatment. All-cause death included vascular death and non-vascular death.

  • Event Rate of Adjudicated Major Bleeding [ Time Frame: Up to 2 days after the last dose ] [ Designated as safety issue: Yes ]
    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.

  • Event Rate Adjudicated Non-major Clinically Relevant Bleeding [ Time Frame: Up to 2 days after the last dose ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 1280
Study Start Date: June 2007
Study Completion Date: January 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rivaroxaban (Xarelto, BAY59-7939)
Participants received once daily (OD) a rivaroxaban 15 mg tablet and a warfarin placebo tablet during the double-blind treatment period
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)
Drug: Warfarin placebo
Participants orally administered a warfarin placebo tablet (adjusted based upon sham INR values)
Active Comparator: Warfarin
Participants received OD a warfarin potassium tablet and a rivaroxaban placebo tablet during the double-blind treatment period
Drug: 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)
Drug: Rivaroxaban placebo
Participants orally administered a rivaroxaban placebo tablet

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00494871

  Hide Study Locations
Locations
Japan
Kasugai, Aichi, Japan, 487-0013
Nagoya, Aichi, Japan, 455-8530
Nagoya, Aichi, Japan, 453-8511
Nagoya, Aichi, Japan, 457-8510
Nagoya, Aichi, Japan, 462-0825
Nagoya, Aichi, Japan, 454-8502
Okazaki, Aichi, Japan, 444-8553
Goshogawara, Aomori, Japan, 037-0053
Hirosaki, Aomori, Japan, 036-8082
Hirosaki, Aomori, Japan, 036-8545
Asahi, Chiba, Japan, 289-2511
Funabashi, Chiba, Japan, 274-8503
Imba, Chiba, Japan, 270-1694
Matsudo, Chiba, Japan, 271-0077
Matsudo, Chiba, Japan, 270-2251
Yotsukaido, Chiba, Japan, 284-0032
Imabari, Ehime, Japan, 799-1592
Matsuyama, Ehime, Japan, 791-8026
Matsuyama, Ehime, Japan, 790-0024
Matsuyama, Ehime, Japan, 790-0925
Niihama, Ehime, Japan, 792-8543
Saijo, Ehime, Japan, 793-0030
Toon, Ehime, Japan, 791-0281
Chikushi-gun, Fukuoka, Japan, 811-1244
Chikushino, Fukuoka, Japan, 818-8516
Chikushino, Fukuoka, Japan, 818-8502
Kasuga, Fukuoka, Japan, 816-0864
Kasuga, Fukuoka, Japan, 816-0833
Kitakyushu, Fukuoka, Japan, 800-0057
Kitakyushu, Fukuoka, Japan, 806-8501
Kurume, Fukuoka, Japan, 830-8577
Ogori, Fukuoka, Japan, 838-0141
Yame, Fukuoka, Japan, 834-0006
Yame, Fukuoka, Japan, 834-0004
Koriyama, Fukushima, Japan, 963-8052
Ogaki, Gifu, Japan, 503-8502
Maebashi, Gunma, Japan, 371-8511
Mebashi, Gunma, Japan, 371-0014
Otake, Hiroshima, Japan, 739-0696
Asahikawa, Hokkaido, Japan, 078-8214
Chitose, Hokkaido, Japan, 066-0034
Hakodate, Hokkaido, Japan, 040-8611
Muroran, Hokkaido, Japan, 051-8501
Otaru, Hokkaido, Japan, 047-8510
Sapporo, Hokkaido, Japan, 065-0027
Sapporo, Hokkaido, Japan, 065-8611
Sapporo, Hokkaido, Japan, 060-0061
Sapporo, Hokkaido, Japan, 064-8570
Sapporo, Hokkaido, Japan, 060-8570
Sapporo, Hokkaido, Japan, 004-0052
Sapporo, Hokkaido, Japan, 065-0033
Sapporo, Hokkaido, Japan, 060-0033
Sapporo, Hokkaido, Japan, 064-0807
Sunagawa, Hokkaido, Japan, 073-0196
Tomakomai, Hokkaido, Japan, 053-8506
Kobe, Hyogo, Japan, 651-1145
Kobe, Hyogo, Japan, 651-0073
Kobe, Hyogo, Japan, 652-0803
Higashiibaraki, Ibaraki, Japan, 311-3193
Hitachi, Ibaraki, Japan, 317-0077
Joso, Ibaraki, Japan, 303-0016
Kasama, Ibaraki, Japan, 309-1793
Moriya, Ibaraki, Japan, 302-0112
Namegata, Ibaraki, Japan, 311-3516
Toride, Ibaraki, Japan, 302-0022
Kanazawa, Ishikawa, Japan, 920-8650
Nomi, Ishikawa, Japan, 923-1100
Hanamaki, Iwate, Japan, 025-0075
Morioka, Iwate, Japan, 020-0103
Marugame, Kagawa, Japan, 763-8502
Takamatsu, Kagawa, Japan, 760-0018
Izumi, Kagoshima, Japan, 899-0131
Atsugi, Kanagawa, Japan, 243-8551
Fujisawa, Kanagawa, Japan, 251-8550
Fujisawa, Kanagawa, Japan, 251-0041
Kamakura, Kanagawa, Japan, 247-8533
Kawasaki, Kanagawa, Japan, 216-8511
Yokohama, Kanagawa, Japan, 236-0037
Yokohama, Kanagawa, Japan, 231-8682
Yokohama, Kanagawa, Japan, 236-0051
Yokohama, Kanagawa, Japan, 227-0046
Nangoku, Kochi, Japan, 783-8509
Uji, Kyoto, Japan, 611-0042
Kuwana, Mie, Japan, 511-0068
Sendai, Miyagi, Japan, 983-0821
Sendai, Miyagi, Japan, 983-8520
Sendai, Miyagi, Japan, 983-8512
Sendai, Miyagi, Japan, 980-0803
Sendai, Miyagi, Japan, 981-3107
Komoro, Nagano, Japan, 384-8588
Matsumoto, Nagano, Japan, 390-8510
Suwa, Nagano, Japan, 392-8510
Joetsu, Niigata, Japan, 949-3193
Nagaoka, Niigata, Japan, 940-8621
Beppu, Oita, Japan, 874-0011
Beppu, Oita, Japan, 874-0901
Yufu, Oita, Japan, 879-5593
Kasaoka, Okayama, Japan, 714-0043
Shimajiri, Okinawa, Japan, 901-0493
Daito, Osaka, Japan, 574-0074
Higashiosaka, Osaka, Japan, 578-8588
Hirakata, Osaka, Japan, 573-8511
Hirakata, Osaka, Japan, 573-0153
Kawachinagano, Osaka, Japan, 586-8521
Kishiwada, Osaka, Japan, 596-8522
Takatsuki, Osaka, Japan, 569-1096
Toyonaka, Osaka, Japan, 560-0022
Yao, Osaka, Japan, 581-0011
Hanyu, Saitama, Japan, 348-8505
Kasukage, Saitama, Japan, 344-0035
Kitamoto, Saitama, Japan, 364-8501
Tokorozawa, Saitama, Japan, 359-1141
Tokorozawa, Saitama, Japan, 359-1142
Wako, Saitama, Japan, 351-0102
Kusatsu, Shiga, Japan, 525-8585
Fujinomiya, Shizuoka, Japan, 418-0076
Fukuroi, Shizuoka, Japan, 437-0061
Hamamatsu, Shizuoka, Japan, 433-8558
Hamamatsu, Shizuoka, Japan, 432-8580
Iwata, Shizuoka, Japan, 438-8550
Shimada, Shizuoka, Japan, 427-8502
Naruto, Tokushima, Japan, 772-8503
Edogawa-ku, Tokyo, Japan, 133-0052
Hachioji, Tokyo, Japan, 192-0045
Higashikurume, Tokyo, Japan, 203-0033
Itabashi-ku, Tokyo, Japan, 173-8610
Itabashi-ku, Tokyo, Japan, 175-0082
Meguro-ku, Tokyo, Japan, 153-8515
Ota-ku, Tokyo, Japan, 145-0065
Shibuya-ku, Tokyo, Japan, 150-0013
Shinagawa-ku, Tokyo, Japan, 141-0001
Shinjuku-ku, Tokyo, Japan, 162-8655
Higashikawada, Yamagata, Japan, 999-7782
Shimonoseki, Yamaguchi, Japan, 750-0061
Shunan, Yamaguchi, Japan, 745-8522
Fukui, Japan, 910-0067
Fukuoka, Japan, 813-0044
Fukuoka, Japan, 810-8563
Fukuoka, Japan, 814-0180
Fukuoka, Japan, 811-0213
Gifu, Japan, 500-8225
Kagoshima, Japan, 891-0116
Kumamoto, Japan, 860-0008
Kyoto, Japan, 602-8026
Nagasaki, Japan, 850-8555
Oita, Japan, 870-0192
Oita, Japan, 870-0263
Oita, Japan, 870-0021
Oita, Japan, 870-0917
Okayama, Japan, 700-8607
Okayama, Japan, 700-8558
Okinawa, Japan, 904-8585
Osaka, Japan, 530-0001
Osaka, Japan, 537-0011
Osaka, Japan, 530-8480
Osaka, Japan, 558-8558
Osaka, Japan, 540-0006
Osaka, Japan, 558-0011
Shizuoka, Japan, 422-8527
Shizuoka, Japan, 424-8636
Shizuoka, Japan, 421-0193
Tokushima, Japan, 770-0011
Tottori, Japan, 689-0203
Toyama, Japan, 930-0194
Wakayama, Japan, 640-8505
Sponsors and Collaborators
Bayer
Janssen R&D, L.L.C.
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Publications:

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00494871     History of Changes
Other Study ID Numbers: 12620
Study First Received: June 29, 2007
Results First Received: March 28, 2012
Last Updated: March 17, 2014
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Bayer:
BAY59-7939
Rivaroxaban
Non-Valvular Atrial Fibrillation
Japanese Patients
Phase III
12620

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Cardiovascular Diseases
Heart Diseases
Pathologic Processes
Rivaroxaban
Warfarin
Anticoagulants
Hematologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014