Evaluation of Cerebral Thrombembolism After TAVR

Aortic Valve Stenosis Clinical Trial

— EARTH - TAVR  

Official title:

Evaluation of Cerebral Thrombembolism After TAVR

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02758964
• Other study ID #: EARTH - TAVR 01
• Status: Completed
• Start date: September 2016
• Est. completion date: January 2019

Study information

• Verified date: March 2019
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: January 2019
• Est. primary completion date: January 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aortic Valve Stenosis
• Embolism
• Intracranial Embolism
• Transcatheter Aortic Valve Replacement

Intervention

Other:
• MRI, neurocognitive Testing
A cerebral MRI and neurocognitive testing will be performed before TAVR, before hospital discharge and after 3 months

Locations

Country	Name	City	State
Germany	Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin	Berlin
Germany	Charité - Universitätsmedizin Berlin, Campus Mitte	Berlin

Sponsors (2)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	Bayer

Country where clinical trial is conducted

Germany, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Evaluation of possible changes in quality of life after TAVI with EQ-5D questionnaire sum score.		Baseline versus 3 months following TAVR

External Links

•   GALILEO main study
•   GALILEO study