Clinical trial NCT03001960: Dual AntiPlatelet Therapies for Prevention of Periinterventional Embolic Events in TAVI
Official title: Dual AntiPlatelet Therapies for Prevention of Periinterventional Embolic Events in Transcatheter Aortic Valve Implantation (TAVI)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Aortic Valve Stenosis
Transcatheter Aortic Valve Replacement
Intracranial Embolism
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Prof. Dr. Jochen Fiebach, Center for Stroke Research Berlin (CSB), Charité - Universitaetsmedizin Berlin
First posted: 2016-12-23
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Total volume of new cerebral lesions on MRI after TAVI versus Baseline
timeFrame: Total volume of new cerebral lesions on MRI, 24-72h after TAV versus Baseline
Secondary outcomes:
measure: New lesion volume of cerebral embolization in patients treated with ASS and Clopidogrel before versus after TAVI
timeFrame: 24-72h post TAVI versus baseline
measure: location of new cerebral lesions early AFTER TAVI
timeFrame: 24-72h after TAVI
measure: extent of new cerebral lesions early AFTER TAVI
timeFrame: 24-72h after TAVI
measure: Assessment of different neurocognitive tests before and after TAVI procedure
timeFrame: 24-72 h after TAVI
measure: Extent of clinically apparent non-cerebral emboli after TAVI
timeFrame: 24-72 h after TAVI
measure: localization of clinically apparent non-cerebral emboli after TAVI
timeFrame: 24-72 h after TAVI
measure: Evaluation of possible changes in quality of life after TAVI with EQ-5D questionnaire sum score.
timeFrame: 24-72 h after TAVI
Other outcomes:
Locations:
Study officials:
References:
citation: Holmes DR Jr, Brennan JM, Rumsfeld JS, Dai D, O'Brien SM, Vemulapalli S, Edwards FH, Carroll J, Shahian D, Grover F, Tuzcu EM, Peterson ED, Brindis RG, Mack MJ; STS/ACC TVT Registry. Clinical outcomes at 1 year following transcatheter aortic valve replacement. JAMA. 2015 Mar 10;313(10):1019-28. doi: 10.1001/jama.2015.1474.
citation: Osnabrugge RL, Mylotte D, Head SJ, Van Mieghem NM, Nkomo VT, LeReun CM, Bogers AJ, Piazza N, Kappetein AP. Aortic stenosis in the elderly: disease prevalence and number of candidates for transcatheter aortic valve replacement: a meta-analysis and modeling study. J Am Coll Cardiol. 2013 Sep 10;62(11):1002-12. doi: 10.1016/j.jacc.2013.05.015. Epub 2013 May 30.