Dual AntiPlatelet Therapies for Prevention of Periinterventional Embolic Events in TAVI (DAPT-TAVI)

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

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).

Study Overview

• Status: Unknown
• Conditions: Aortic Valve Stenosis; Transcatheter Aortic Valve Replacement; Intracranial Embolism
• Intervention / Treatment: Drug: Preloading before TAVI; Drug: Postloading after 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.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1- PREloading BEFORE TAVI; 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; Preloading with Aspirin and Clopidogrel before TAVI; Other Names: ASS, Plavix
Experimental: Group 2 - POSTLoading AFTER TAVI; 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; Postloading with Aspirin and Clopidogrel after TAVI; Other Names: ASS, Plavix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: Prof. Dr. Jochen Fiebach, Center for Stroke Research Berlin (CSB), Charité - Universitaetsmedizin Berlin

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2017
• Primary Completion (Anticipated): March 1, 2018
• Study Completion (Anticipated): April 1, 2018

Study Registration Dates

• First Submitted: December 18, 2016
• First Submitted That Met QC Criteria: December 20, 2016
• First Posted (Estimate): December 23, 2016

Study Record Updates

• Last Update Posted (Estimate): December 28, 2016
• Last Update Submitted That Met QC Criteria: December 27, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Embolism and Thrombosis; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Intracranial Embolism and Thrombosis; Thromboembolism; Embolism; Aortic Valve Stenosis; Intracranial Embolism; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel
• Other Study ID Numbers: DAPT-TAVI 01