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Xarelto

Phase 3

Atrial Fibrillation | Small molecule | Cardiovascular |Bayer AG|Last Updated: Jul 25, 2016

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindACTIVE_CONTROLLEDDMC
Total Trials6
Total Enrollment3,082

FDA Designations

No designations recorded

Clinical trial landscape

Xarelto · 6 trials · 1 indication

Phase 3 3Phase 2 3
NCT01839357Exploring the Efficacy of Once Daily Oral Rivaroxaban for Treatment of Thrombus in Left Atrial/Left Atrial Appendage in Subjects With Nonvalvular Atrial Fibrillation or Atrial FlutterAtrial Fibrillation
COMPLETED60 Analytics
NCT01674647Explore the Efficacy and Safety of Once-daily Oral Rivaroxaban for the Prevention of Cardiovascular Events in Subjects With Nonvalvular Atrial Fibrillation Scheduled for CardioversionAtrial Fibrillation
COMPLETED1,504 Analytics
NCT00494871Efficacy and Safety of Rivaroxaban for the Prevention of Stroke in Subjects With Non-Valvular Atrial FibrillationAtrial Fibrillation
COMPLETED1,280 Analytics
PHASE3COMPLETED
Exploring the Efficacy of Once Daily Oral Rivaroxaban for Treatment of Thrombus in Left Atrial/Left Atrial Appendage in Subjects With Nonvalvular Atrial Fibrillation or Atrial Flutter
Atrial FibrillationUnlock trial analytics
PHASE3COMPLETED
Explore the Efficacy and Safety of Once-daily Oral Rivaroxaban for the Prevention of Cardiovascular Events in Subjects With Nonvalvular Atrial Fibrillation Scheduled for Cardioversion
Atrial FibrillationUnlock trial analytics
PHASE3COMPLETED
Efficacy and Safety of Rivaroxaban for the Prevention of Stroke in Subjects With Non-Valvular Atrial Fibrillation
Atrial FibrillationUnlock trial analytics

Study Endpoints

Primary Endpoints

The percentage of subjects with complete resolution of left atrial or left atrial appendage thrombus at the end of treatment
After 6 weeks

Complete resolution is characterized as the subject is completely thrombus-free confirmed on transesophageal echocardiography

Number of Participants With Composite of the Following Events, Adjudicated Centrally: Stroke, Transient Ischemic Attack, Non-central Nervous System Systemic Embolism, Myocardial Infarction and Cardiovascular Death
From randomization to the date of last dose of study drug +2 days for subjects who completed planned treatment or the earlier date [last planned dose, follow-up visit at the end of 30-day follow-up period] for subjects who prematurely stopped treatment

Stroke, TIA, Non-CNS Embolism, MI and cardiovascular death were adjudicated and confirmed by Clinical Endpoints Committee (CEC). Stroke included hemorrhagic and ischemic infarction. TIA including information if with or without matching lesion. Non CNS systemic embolism included emboli in peripheral arterial of the upper and lower extremities, ocular and retinal (pulmonary embolism and MI were excluded from the category). MI was assessed based on either cardiac biomarkers, new abnormal Q waves appeared on electrocardiogram for \>= 2 leads, or autopsy confirmation. Cardiovascular death included death in subjects with non-valvular atrial fibrillation (AF). Number of subjects with composite events were reported.

Number of Participants With Major Bleedings as Per Central Adjudication
From randomization up to the date of the last dose of study drug + 2 days

Bleeding events were adjudicated and confirmed by CEC blinded to treatment. The CEC categorized the bleeding events as major or non-major. The bleeding events were defined per the International Society on Thrombosis and Hemostasis (ISTH) criteria. Major bleeding was clinically overt bleeding associated with a fall in hemoglobin of 2 gram per deciliter (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. Number of subjects with confirmed adjudicated bleeding events occurring in greater than (\>)1 total subjects were reported.

Event Rate of the Composite Endpoint of Adjudicated Major Bleeding or Adjudicated Non-major Clinically Relevant Bleeding
Up to 2 days after the last dose

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.

(Safety) Incidence of bleeding
Throughout treatment and followup period
(PK/PD) BAY 59-7939 concentrations / Factor Xa activity, PT, PT-INR, PTT and HEPTEST
Day 14 and Day 28
Pharmacokinetics (PK) CL/f, AUC, Cmax, Pharmacodynamics (PD), Factor Xa activity, PT, PT-INR, aPTT and HEPTEST(R)
Day 14 and 28

Secondary Endpoints

Categories of thrombus outcome in subjects: resolved, reduced, unchanged, enlarged or new
After 6 weeks
The composite number of stroke and non-central nervous system systemic embolism events
Up to 12 weeks
The number of all bleeding events
Up to 12 weeks
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Study Design & Arms

AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
RivaroxabanEXPERIMENTAL -
Rivaroxaban (Xarelto, BAY59-7939)EXPERIMENTALA Direct Cardioversion Strategy can be performed only if sufficient anticoagulation is proven during the last 21 days prior to randomization and/or a transesophageal echocardiogram (TEE) is planned before cardioversion. Rivaroxaban will be given for 1-5 days before planned direct cardioversion. The run-in of 1-5 days is needed due to potential pretreatment with VKA. Treatment with rivaroxaban will be continued for 42 days after the cardioversion. A Delayed Cardioversion Strategy will be chosen if sufficient anticoagulation is not proven during the last 21 days prior to randomization and no TEE is planned. Rivaroxaban will be given for at least 21 (+4) days before the planned cardioversion, to a maximum of 56 (+4) days prior to planned cardioversion.
Vitamin K antagonist (VKA)ACTIVE_COMPARATORA Direct Cardioversion Strategy can be performed only if sufficient anticoagulation is proven during the last 21 days prior to randomization and/or a transesophageal echocardiogram (TEE) is planned before cardioversion. VKA will be given for 1-5 days before planned direct cardioversion. The run-in of 1-5 days is needed due to potential pretreatment with VKA. Treatment with VKA will be continued for 42 days after the cardioversion. A Delayed Cardioversion Strategy will be chosen if sufficient anticoagulation is not proven during the last 21 days prior to randomization and no TEE is planned. VKA will be given for at least 21 (+4) days before the planned cardioversion, to a maximum of 56 (+4) days prior to planned cardioversion.
WarfarinACTIVE_COMPARATORParticipants received OD a warfarin potassium tablet and a rivaroxaban placebo tablet during the double-blind treatment period
Arm 1EXPERIMENTAL -
Arm 2EXPERIMENTAL -
Arm 4ACTIVE_COMPARATOR -
Arm 3EXPERIMENTAL -

Interventions

NameTypeDescription
Rivaroxaban (Xarelto, BAY59-7939)DRUGRivaroxaban 20 mg orally once daily for 6 weeks; subjects with severe to moderate renal impairment (ie, CrCl of 15 to 49 mL/min, inclusive) will receive the adjusted dose of 15 mg orally once daily for 6 weeks in the study.
Vitamin K antagonist (VKA)DRUGVKA orally once daily titrated to a target international normalized ratio (INR) of 2.5 (range 2.0-3.0, inclusive); the VKA type (eg, warfarin, acenocoumarol, phenprocoumon, fluindione, etc) will be assigned by the investigator according to local treatment standards
WarfarinDRUGParticipants 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 placeboDRUGParticipants orally administered a rivaroxaban placebo tablet
Warfarin placeboDRUGParticipants orally administered a warfarin placebo tablet (adjusted based upon sham INR values)
Xarelto (Rivaroxaban, BAY59-7939)DRUG10mg od
Rivaroxaban (BAY59-7939)DRUG10mg BID, Semi-sequential, dose escalation.
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites31

Inclusion Criteria: * Men or women aged \>/= 18 years * Hemodynamically stable nonvalvular AF or atrial flutter * LA/LAA thrombus documented at baseline by transesophageal echocardiography (TEE) up to 72 hours prior to start of study medication * vitamin K antagonist(s) (VKA)/ new oral anticoagulan...

Countries:BulgariaFranceGermanyPolandRussiaTurkey (Türkiye)UkraineUnited StatesBelgiumBrazilCanadaChinaDenmarkFinlandGreeceItalyNetherlandsPortugalSingaporeSouth AfricaSpainUnited KingdomJapan
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Frequently asked questions about Xarelto

What is Rivaroxaban used for?

Rivaroxaban is a small molecule drug being developed for several thromboembolic disorders. Its indications include prevention and control of thromboembolic disorders, pulmonary embolism, superficial vein thrombosis, and pharmacokinetics. It has been studied in clinical trials for the prevention of venous thromboembolism in patients undergoing orthopedic surgery, such as total hip and knee replacement.

Who makes Rivaroxaban?

Rivaroxaban is developed by Bayer AG, a company traded under the ticker BAYRY. The drug has been investigated in multiple clinical trials, including Phase 3 studies for the prevention of venous thromboembolism and for reducing major cardiovascular events in patients with coronary or peripheral artery disease.

What phase is Rivaroxaban in?

Rivaroxaban is currently listed as being in Phase 1 of clinical development. However, it has completed 10 clinical trials, including several Phase 3 studies. These completed trials have investigated its use for the prevention of venous thromboembolism in surgical patients and for the prevention of major cardiovascular events in patients with artery disease.

What clinical trials is Rivaroxaban in?

Rivaroxaban has been studied in several clinical trials, including NCT00332020, which examined its use in preventing venous thromboembolism after total hip replacement, and NCT00361894, which studied its use after total knee replacement. Another trial, NCT01776424, investigated rivaroxaban for preventing major cardiovascular events in patients with coronary or peripheral artery disease.

Is Rivaroxaban the same as BAY 59-7939?

Yes, Rivaroxaban is also known as BAY 59-7939. Clinical trials such as NCT00332020 and NCT00361894 refer to the drug as BAY 59-7939 in their titles. These studies investigated the drug for the prevention of venous thromboembolism in patients undergoing elective total hip or knee replacement surgery.