Dual AntiPlatelet Therapies for Prevention of Periinterventional Embolic Events in TAVI

Study Overview
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Brief Summary
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TAVI is increasingly adopted as standard treatment for many subgroups of patients with aortic stenosis. However, due to a lack of data there is yet no TAVI-specific guidance regarding the optimum periinterventional drug regimen. The study evaluates the effect of dual antiplatelet pretreatment on periinterventional embolic cerebral lesions and bleeding complications in patients undergoing transfemoral aortic valve implantation (TF-TAVI).

Detailed Description
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Patients undergoing TAVI bear a high risk of ischaemic stroke, which is an independent predictor of mortality1. Dual antiplatelet therapy (DAPT) is recommended by current guidelines without clear specifications on the time of initiation of treatment due to a lack of data. While some centers initiate DAPT with aspirin and clopidogrel prior to TAVI to reduce the rate of periinterventional embolic events, others start these medications after the procedure.Data on antithrombotic therapy during TAVI are scarce and no randomized evaluation has been performed to demonstrate what the best strategy is during the procedure. Therefore, the objective of this clinical trial is to assess the efficacy of pre- versus postoperative dual antiplatelet loading with Aspirin and Clopidogrel on volume of periinterventional cerebral ischemic lesions as quantified by diffusion weight MRI (DW-MRI) and neurocognitive function in patients undergoing transfemoral aortic valve replacement. The statistical trial design assumes superiority of preloading with DAPT regarding the primary endpoint.

Official Title
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Dual AntiPlatelet Therapies for Prevention of Periinterventional Embolic Events in Transcatheter Aortic Valve Implantation (TAVI)

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

Intervention / Treatment
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* Drug: Preloading before TAVI
* Drug: Postloading after TAVI


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients >18 years and <90 years Patients undergoing TF-TAVI for severe aortic stenosis (combined with aortic regurgitation) Informed consent Exclusion criteria: TIA/Stroke within last 90 days Aortic valve-in-valve procedures TAVI for treatment of isolated aortic regurgitation known significant carotid stenosis (>70%) Prior myocardial infarction or revascularization with PCI or CABG within past 3 months Clopidogrel and/ or Aspirin within past 7 days any other indication for (dual) antiplatelet therapy Contraindication to MRI (MRI conditional pacemakers accepted!) participation in another interventional trial cardiogenic shock (positive shock index OR need for catecholamine support OR systolic bloodpressure < 90 mmHg) or need for pre-hospital intubation cardiac arrest <90 days prior to randomization Pregnant or lactating females

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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1- PREloading BEFORE TAVI<br>Aspirin 100 mg loading orally 6-12 hours before TAVI and Clopidogrel 600mg loading 6-12 before TAVI followed by maintenance dose of 100mg aspirin and 75mg clopidogrel per day | Drug: Preloading before TAVI<br>* Preloading with Aspirin and Clopidogrel before TAVI<br>* Other names: ASS, Plavix;|
| Experimental: Group 2 - POSTLoading AFTER TAVI<br>Aspirin 100 mg loading orally 6-12 hours after TAVI and Clopidogrel 600mg loading 6-12 hours after TAVI followed by maintenance dose of 100mg aspirin and 75mg clopidogrel per day | Drug: Postloading after TAVI<br>* Postloading with Aspirin and Clopidogrel after TAVI<br>* Other names: ASS, Plavix;|

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 after TAVI versus Baseline |  | Total volume of new cerebral lesions on MRI, 24-72h after TAV versus Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| New lesion volume of cerebral embolization in patients treated with ASS and Clopidogrel before versus after TAVI | Total new lesion volume is defined as the sum volume of all new cerebral ischemic lesions on the post-procedural MRI relative to the pre-TAVR cerebral MRI scan (on diffusion weighted and FLAIR MRI images). | 24-72h post TAVI versus baseline | 
| location of new cerebral lesions early AFTER TAVI | To evaluate cerebral embolisation, which is not procedure related, cerebral embolisation on MRI will be before TAVI versus the post-TAVI MRI scan | 24-72h after TAVI | 
| extent of new cerebral lesions early AFTER TAVI | To evaluate cerebral embolisation, which is not procedure related, cerebral embolisation on MRI will be before TAVI versus the post-TAVI MRI scan | 24-72h after TAVI | 
| Assessment of different neurocognitive tests before and after TAVI procedure | To evaluate neurologic function with a battery of neurocognitive tests and to correlate these findings to cerebral MRI scans | 24-72 h after TAVI | 
| Extent of clinically apparent non-cerebral emboli after TAVI | To describe extent and localization of non-cerebral embolisation (e.g. pulmonary embolism, limb ischaemia...) | 24-72 h after TAVI | 
| localization of clinically apparent non-cerebral emboli after TAVI | To describe extent and localization of non-cerebral embolisation (e.g. pulmonary embolism, limb ischaemia...) | 24-72 h after TAVI | 
| Evaluation of possible changes in quality of life after TAVI with EQ-5D questionnaire sum score. |  | 24-72 h after TAVI |