Clinical trial NCT02758964: Evaluation of Cerebral Thrombembolism After TAVR
Official title: Evaluation of Cerebral Thrombembolism After TAVR
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Aortic Valve Stenosis
Transcatheter Aortic Valve Replacement
Intracranial Embolism
Keywords: TAVR
TAVI
Transcatheter Aortic Valve Replacement
Intracranial Embolism
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2016-05-03
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients 18 years or older wirth aortic valve stenosis receiving TAVR-Intervention.

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Total volume of new cerebral lesions on MRI, 3 months after TAVR versus Baseline
timeFrame: 3 months after TAVR versus baseline
Secondary outcomes:
measure: New lesion volume of cerebral embolization in patients treated with ASS and rivaroxaban 10mg OD versus an antiplatelet -based strategy with ASS and clopidogrel.
timeFrame: 3 months post TAVR versus baseline
measure: extent and location of new cerebral lesions early AFTER TAVR and after 3 months
timeFrame: MRI after TAVR (0-7 days after TAVR) compared to 3 months after TAVR
measure: 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.
timeFrame: Before TAVR, post TAVR and after 3 months
measure: Extent and localization of clinically apparent non-cerebral emboli after TAVR
timeFrame: baseline, post TAVR and after 3 months
measure: Evaluation of possible changes in quality of life after TAVI with EQ-5D questionnaire sum score.
timeFrame: Baseline versus 3 months following TAVR
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin, Campus Mitte
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin
Study officials:
affiliation: Charité - Universitätsmedizin Berlin, Department of Cardiology
name: Ulf Landmesser, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Charité - Universitätsmedizin Berlin, Department of Neurology
name: Matthias Endres, Prof. Dr.
role: STUDY_CHAIR
affiliation: Charité - Universitätsmedizin Berlin, Department of Cardiology
name: Georg M Fröhlich, PD
role: STUDY_CHAIR
affiliation: German Heart Institute
name: Volkmar Falk, Professor
role: STUDY_CHAIR
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.