Patients with severe aortic stenosis that require Transcatheter aortic valve replacement are at risk for stroke. This study is to evaluate the occurrence and extent of cerebral embolization (total new lesion volume) in patients before TAVR versus 3 months after TAVR. MedDRA version: 19.0 Level: PT Classification code 10002916 Term: Aortic valve replacement System Organ Class: 10042613 - Surgical and medical procedures
Conditions
Interventions
Sponsors
Charité Universitätsmedizin Berlin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Potential patients must satisfy the following criteria to be enrolled in the study: - Man or woman of 18 years of age or older, who are planned for TAVR - TAVR of a native aortic valve stenosis - By iliofemoral or subclavian access - With any approved/marketed TAVR device - EARTH Written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 23 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 207
Exclusion criteria
Exclusion criteria: Patients are NOT eligible to participate in this study 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) 3. Any contraindication for cerebral MRI, in particular: - non-MRI-conditional pacemakers - MRI conditional pacemakers <4 weeks after implant - any metal fragments in the eye - aneurysm clip in the brain - severe claustrophobia Bleeding risks or systemic conditions 4. 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 5. Any indication for dual-antiplatelet therapy (DAPT) for more than 3 months’ after TAVR (such as coronary, carotid or peripheral stent implantation) 6. 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 7. Routine use of oral non-steroidal anti-inflammatory drugs (NSAID) 8. Concomitant therapy with systemic drugs that are strong inhibitors of both CYP3A4 and P-gp (azole antimycotics such as ketoconazole and itraconazole or HIV protease inhibitors such as ritonavir) 9. Concomitant therapy with drugs that are strong CYP 3A4 inducers (e.g. carbamazepine, phenytoin, rifampin, St. John’s wort) 10. Concomitant therapy with omeprazole or esomeprazole that cannot be switched to an alternate medication. Concomitant conditions 11. Planned coronary or vascular intervention or major surgery 12. Clinically overt stroke within the last 3 months 13. Severe renal impairment (eGFR < 30 mL/min/1.73 m2) or on dialysis before TAVR, or unresolved kidney injury with renal dysfunction stage 2 or higher 14. Moderate and severe hepatic impairment (Child-Pugh Class B or C) or any hepatic disease associated with coagulopathy 15. Active infective endocarditis 16. Active malignancy (diagnosed within 5 years) except for adequately treated Nonmelanoma skin cancer or other non-invasive or in situ neoplasm (e.g.,cervical cancer in situ that has been successfully treated) Other exclusion criteria 17. Dementia or forgetfulness hindering compliance with medication intake or other Study procedures 18. Legally incompetent to provide IC 19. Previous (30 days before enrolment) or concomitant participation in another clinical study with investigational medicinal product(s). 20. Previous assignment to treatment during this study 21. 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 22. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the occurrence and extent of cerebral embolization (total new lesion volume) in patients before TAVR versus 3 months after TAVR by cerebral MRI scans.;Secondary Objective: Objectives analysed in the patient group included in EARTH TAVR and GALILEO: To describe for this patient population and for both treatment groups (from GALILEO) separately: - to compare cerebral embolization in patients on a Rivaroxaban-based strategy with ASS and rivaroxaban 10mg OD versus an antiplatelet –based strategy with ASS/Clopidogrel 3 months after TAVR - extent and location of new cerebral lesions early after TAVR and after 3 months - possible changes in neurocognitive and neurologic function after TAVR - extent and localization of clinically apparent non-cerebral emboli after TAVR - possible changes in quality of life after TAVR Additional secondary objectives can be found in the study protocol.;Primary end point(s): Occurrence and extent of cerebral embolization (total new lesion volume) in patients 3 months after TAVR. Total new lesion volume is defined as the sum volume of all new cerebral ischemic lesions on the 3 months post-procedural MRI relative to the pre-TAVR cerebral MRI scan (on diffusion weighted and FLAIR MRI images). ;Timepoint(s) of evaluation of this end point: Potential TAVR candidates will be included into the EARTH TAVR study and receive a pre- and a post-TAVR MRI examination. Only patients, who are finally included into the GALILEO trial AND receive the 3 months’ follow-up MRI scan will contribute to the main objective. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Occurrence and extent of cerebral embolization (total new lesion volume) in patients 3 months after TAVR. Total new lesion volume is defined as the sum volume of all new cerebral ischemic lesions on the 3 months post-procedural MRI relative to the pre-TAVR cerebral MRI scan (on diffusion weighted and FLAIR MRI images). ;Timepoint(s) of evaluation of this end point: Potential TAVR candidates will be included into the EARTH TAVR study and receive a pre- and a post-TAVR MRI examination. Only patients, who are finally included into the GALILEO trial AND receive the 3 months’ follow-up MRI scan will contribute to the main objective. | — |
Countries
Germany
Contacts
Public ContactClinical Trials Contact
Charité Universitätsmedizin Berlin
Outcome results
None listed