Patients with severe aortic stenosis that require Transcatheter aortic valve replacement are at risk of thrombus formation. Rivaroxaban (oral-anticoagulant) may reduce this risk, without increasing bleeding risk MedDRA version: 19.0 Level: PT Classification code 10002916 Term: Aortic valve replacement System Organ Class: 10042613 - Surgical and medical procedures
Conditions
Interventions
Sponsors
Bayer AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Potential subjects must satisfy the following criteria to be enrolled in the study: • Man or woman of 18 years of age or older • Have a successful TAVR of a native aortic valve Stenosis (either native or valve-in-valve) • Via iliofemoral or subclavian access • With any approved/marketed TAVR device • Provide written IC Successful TAVR (29) is defined: 1. Correct positioning of a single prosthetic heart valve into the proper anatomical location. 2. Intended performance of the prosthetic heart valve - presence of all 3 conditions post-TAVR: a. mean aortic valve gradient =65 years) yes F.1.3.1 Number of subjects for this age range 1368
Exclusion criteria
Exclusion criteria: Subjects are NOT eligible to participate in this trial if they meet ANY of the following exclusion criteria: GENERAL 1. Any atrial fibrillation (AF), at the time of randomization or previous, with an ongoing indication for oral anticoagulant treatment 2. Any other indication for continued treatment with any oral anticoagulant (OAC) BLEEDING RISKS OR SYSTEMIC CONDITIONS 3. Known bleeding diathesis, such as but not limited to: a. active internal bleeding, clinically significant bleeding, bleeding at a non-compressible site, or bleeding diathesis, b. platelet count = 50,000/mm3 at screening c. Hemoglobin level < 8.5 g/dL d. history of intracranial hemorrhage or subdural hematoma e. major surgery, biopsy of a parenchymal organ, or serious trauma within 30 days before randomization f. active peptic ulcer or known upper GI bleeding within the last 3 months CONCOMITANT AND STUDY MEDICATION 4. Any ongoing absolute indication for dual-antiplatelet therapy (DAPT) at the time of screening that is unrelated to the TAVR procedure 5. Known hypersensitivity or contraindication to acetylsalicylic acid, clopidogrel or rivaroxaban or hypersensitivity to contrast media that could not be solved neither by switching to an alternate contrast media nor with pre-treatment with appropriate medication 6. Routine use of oral non-steroidal anti-inflammatory drugs (NSAID) 7. Concomitant therapy with systemic drugs that are strong inhibitors of both CYP 3A4 and P-gp (azole antimycotics such as ketoconazole and itraconazole or HIV protease inhibitors such as ritonavir) 8. Concomitant therapy with drugs that are strong CYP 3A4 inducers (e.g. carbamazepine, phenytoin, rifampin, St. John’s wort) 9. Concomitant therapy with omeprazole or esomeprazole that cannot be switched to an alternate medication. Concomitant conditions 10. Planned coronary or vascular intervention or major surgery 11. Clinically overt stroke within the last 3 months 12. Severe renal impairment (eGFR < 30 mL/min/1.73 m2) or on dialysis, or post-TAVR unresolved acute kidney injury with renal dysfunction stage 2 or higher 13. Moderate and severe hepatic impairment (Child-Pugh Class B or C) or any hepatic disease associated with coagulopathy 14. Active infective endocarditis 15. Active malignancy (diagnosed within 5 years) except for adequately treated non-melanoma skin cancer or other non-invasive or in situ neoplasm (e.g., cervical cancer in situ that has been successfully treated or non-active prostate cancer) OTHER EXCLUSION CRITERIA 16. Dementia or forgetfulness hindering compliance with medication intake or other study procedures 17. Legally incompetent to provide IC 18. Previous (30 days before enrolment) or concomitant participation in another clinical study with investigational medicinal product(s). 19. Previous assignment to treatment during this study 20. Close affiliation with the investigational site; e.g. a close relative of the investigator, dependent person (e.g. employee or student of the investigational site) or sponsor 21. Female of childbearing potential a. Who are not surgically sterile, or who are sexually active and not willing to use adequate contraceptive measures with a failure rate less than 1% per year (e.g. oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, male partner sterilization) before entry and throughout the study, or b. For whom a negative pre
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess whether a rivaroxaban-based anticoagulation strategy, following successful TAVR, compared to an antiplatelet-based strategy, is superior in reducing death or first thromboembolic events (DTE). To assess the primary bleeding events (PBE) of the Rivaroxaban-based strategy, following TAVR, compared to an antiplatelet-based strategy.;Secondary Objective: The secondary efficacy objectives are to compare the effects of the rivaroxaban-based strategy and antiplatelet-based strategy with respect to the net-clinical-benefit, defined as the composite of death or first thromboembolic events and life-threatening, disabling, or major bleeding events classified according to the VARC definitions following the BARC classification. Whereas the secondary safety objectives are safety criteria with respect to bleeding (thrombolysis in myocardial infarction [TIMI] major or minor bleeds, international society on thrombosis and haemostasis [ISTH] major bleeding, and BARC 2, 3, or 5 bleeds).;Primary end point(s): The primary efficacy endpoint is death or first adjudicated thromboembolic event (DTE), defined as the adjudicated composite of: • All-cause death • Any stroke • Myocardial infarction (MI) • Symptomatic valve thrombosis • Pulmonary embolism (PE) • Deep vein thrombosis (DVT) • Non-central nervous system (CNS) systemic embolism The primary safety endpoint is primary bleeding event (PBE), defined according to VARC definitions following the BARC classification as the adjudicated composite of: • life-threatening bleed • disabling bleed • major bleed The endpoint definitions and the definitions of terms are located in Sections 16.1 and 16.2 of the protocol, respectively.;Timepoint(s) of evaluation of this end point: Subjects are treated and followed from randomization until the study ends, i.e. when the predefined number of primary efficacy endpoints is reached or earlier if the event rate is unexpectedly low and study closure activities are completed. Th | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints include: • The adjudicated composite of cardiovascular death, any stroke, myocardial infarction, symptomatic valve thrombosis, pulmonary embolism, deep vein thrombosis, or non-CNS systemic embolism • The net-clinical-benefit defined as the adjudicated composite of all-cause death, any stroke, myocardial infarction, symptomatic valve thrombosis, pulmonary embolism, deep vein thrombosis, non-CNS systemic embolism (efficacy); life-threatening, disabling andmajor bleeds (safety). The secondary safety endpoints are bleeding complications according to: • The composite of TIMI major or minor bleeds • ISTH major bleeding • The composite of BARC 2, 3, or 5 bleeding;Timepoint(s) of evaluation of this end point: The secondary endpoints will be evaluated throughout the study, since it is an event driven study and follows intention to treat analysis. | — |
Countries
Austria, Belgium, Canada, Czech Republic, Denmark, France, Germany, Italy, Netherlands, Norway, Poland, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactClinical Trials Contact
Bayer AG
Outcome results
None listed