Evaluation of Cerebral Thrombembolism After TAVR

Study Overview
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Brief Summary
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EARTH-TAVR is a diagnostic multicenter study to evaluate the occurrence and extent of cerebral embolization (total new lesion volume) in patients before TAVR versus 3 months after TAVR.

Detailed Description
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Calcific aortic valve stenosis is the most common cause of aortic stenosis (AS) among adults in Europe and in the United States. The prevalence of moderate or severe AS was found to be age-dependent rising from 0.02% in patients aged 18-44 years to 2.8% in patients aged ≥ 75 years. Among patients at prohibitive surgical risk, TAVR has become the treatment of choice.The safety and efficacy of TAVR compared with medical management and SAVR has been demonstrated in clinical trials.The composite of the rate of all-cause death or stroke was 27% and 37% in TAVR patients after 1 and 2 years, respectively.Even though parts of the strokes occur during the peri-procedural period, the patients remain at risk of stroke throughout the first months after the procedure. EARTH-TAVR is a diagnostic multicenter study performing in association with the GALILEO trial (NCT02556203), which is investigating cerebral embolization with MRI and neurocognitive testing in patients undergoing TAVR, who are treated with anticoagulation (Rivaroxaban/ASS) or DAPT (Clopidogrel/ASS). GALILEO is a global multicenter, open-label, randomized, event-driven, active-controlled study comparing a rivaroxaban-based antithrombotic strategy to an antiplatelet-based strategy after transcatheter aortic valve replacement (TAVR) to optimize clinical outcomes. Investigators aim to investigate peri-interventional and delayed cerebral embolization in the early period (3 months) after TAVR and to analyze associations between neurocognitive parameters and cerebral embolization patterns in patients on different antithrombotic treatment regimes.

Official Title
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Evaluation of Cerebral Thrombembolism After TAVR

Conditions
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Aortic Valve Stenosis, Transcatheter Aortic Valve Replacement, Intracranial Embolism

Intervention / Treatment
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* Other: MRI, neurocognitive Testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Man or woman of 18 years of age or older Via iliofemoral or subclavian access Provide written IC Exclusion Criteria: Atrial fibrillation (AF), current or previous, with an ongoing indication for oral anticoagulant Treatment Any other indication for continued treatment with any oral anticoagulant (OAC) Known bleeding diathesis (such as but not limited to active internal bleeding, clinically significant bleeding, platelet count ≤ 50,000/mm3 at screening, hemoglobin level < 8.5 g/dL, active peptic ulcer or known gastrointestinal (GI) bleeding, history of intracranial hemorrhage or subdural hematoma) Any indication for dual-antiplatelet therapy (DAPT) for more than 3 months after randomization (such as coronary, carotid or peripheral stent implantation) Clinically overt stroke within the last 3 months Planned coronary or vascular intervention or major surgery 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 Moderate and severe hepatic impairment (Child-Pugh Class B or C) or any hepatic disease associated with coagulopathy 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: MRI, neurocognitive Testing|A cerebral MRI and neurocognitive testing will be performed before TAVR, before hospital discharge and after 3 months|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total volume of new cerebral lesions on MRI, 3 months after TAVR versus Baseline | Occurrence and extent of cerebral embolization in patients after TAVR measured by total volume of new ischemic cerebral lesions on DWI and FLAIR MRI. 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) | 3 months after TAVR versus baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| New lesion volume of cerebral embolization in patients treated with ASS and rivaroxaban 10mg OD versus an antiplatelet -based strategy with ASS and clopidogrel. | 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). | 3 months post TAVR versus baseline | 
| extent and location of new cerebral lesions early AFTER TAVR and after 3 months | To evaluate cerebral embolisation, which is not procedure related, cerebral embolisation on MRI will be compared 3 months post TAVR versus the post-TAVR MRI scan | MRI after TAVR (0-7 days after TAVR) compared to 3 months after TAVR | 
| Assessment of different neurocognitive tests (NIHSS-score, MOCA-score, MOT-score, PAL-score, RTI-score, SWM-score, AST-score, CAM-Score); change of sum scores before, after and 3 months after TAVR procedure. | To evaluate neurologic function with a battery of neurocognitive tests and to correlate these findings to cerebral MRI scans | Before TAVR, post TAVR and after 3 months | 
| Extent and localization of clinically apparent non-cerebral emboli after TAVR | To describe extent and localization of non-cerebral embolisation (e.g. pulmonary embolism, limb ischaemia...) | baseline, post TAVR and after 3 months | 
| Evaluation of possible changes in quality of life after TAVI with EQ-5D questionnaire sum score. |  | Baseline versus 3 months following TAVR | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TAVR, TAVI, Transcatheter Aortic Valve Replacement, Intracranial Embolism