Rationale and design of the ADAPT-TAVR trial: a randomised comparison of edoxaban and dual antiplatelet therapy for prevention of leaflet thrombosis and cerebral embolisation after transcatheter aortic valve replacement

Abstract

IntroductionOptimal antithrombotic strategy following transcatheter aortic valve replacement (TAVR) is still unknown. We hypothesised that the direct factor Xa inhibitor edoxaban can potentially prevent subclinical leaflet thrombosis and cerebral embolisation compared with conventional dual antiplatelet therapy (DAPT) in patients undergoing TAVR.Methods and analysisThe ADAPT-TAVR trial is an international, multicentre, randomised, open-label, superiority trial comparing edoxaban-based strategy and DAPT strategy in patients without an indication for oral anticoagulation who underwent successful TAVR. A total of 220 patients are randomised (1:1 ratio), 1–7 days after successful TAVR, to receive either edoxaban (60 mg daily or 30 mg daily if patients had dose-reduction criteria) or DAPT using aspirin (100 mg daily) plus clopidogrel (75 mg daily) for 6 months. The primary endpoint was an incidence of leaflet thrombosis on four-dimensional, volume-rendered cardiac CT imaging at 6 months post-TAVR. The key secondary endpoints were the number of new lesions and new lesion volume on brain diffusion-weighted MRI and the changes in neurological and neurocognitive function assessment between immediate post-TAVR and 6 months of study drug administration. Detailed clinical information on thromboembolic and bleeding events were also assessed.Ethics and disseminationEthic approval has been obtained from the Ethics Committee/Institutional Review Board of Asan Medical Center (approval number: 2017–1317) and this trial is also approved by National Institute of Food and Drug Safety Evaluation of Republic of Korea (approval number: 31511). Results of this study will be disseminated in scientific publication in reputed journals.Trial registration numberNCT03284827.

Edoxaban Versus Dual Antiplatelet Therapy for Leaflet Thrombosis and Cerebral Thromboembolism After TAVR: The ADAPT-TAVR Randomized Clinical Trial

“…The sample size was estimated to simultaneously meet the primary end point of the incidence of leaflet thrombosis on cardiac CT and to meet the key secondary end point of the total new lesion number on brain MRI. 23 From the results from the RESOLVE registry (Assessment of Transcatheter and Surgical Aortic Bioprosthetic Valve Thrombosis and Its Treatment with Anticoagulation) and SAVORY registry (Subclinical Aortic Valve Bioprosthesis Thrombosis Assessed With 4D CT), 9 we assumed an incidence of subclinical leaflet thrombosis of 15% in the DAPT group and 3% in the NOAC (edoxaban) group. It was estimated that 192 patients (96 patients in each arm) would need to be enrolled to provide a statistical power of 80% to detect this difference with a 2-sided significance level of 0.05.…”

“…ADAPT-TAVR was a multinational, multicenter, prospective, randomized, open-label, adjudicator-masked trial. 23 The trial was conducted in compliance with the International Council for Harmonization and the Declaration of Helsinki. The trial protocol was approved by the ethics committees and corresponding health authorities for all participating sites.…”

“…31 The brain MRIs were analyzed for the occurrence, number, and volume of new lesions on the 6-month diffusion-weighted imaging, fluidattenuated inversion recovery, and gradient echo images compared with baseline MRI, respectively. 23 The trial-specific standardized 4-dimensional cardiac CT acquisition protocol and brain MRI protocol are provided in Tables S4 and S5, respectively. All participating sites were qualified for their CT and MRI machines and capability to perform the standardized acquisition protocol by the imaging core laboratory.…”

“…32 Imaging measurements were performed at a central imaging core laboratory (Asan Image Metrics) in a blinded manner by independent cardiac radiologists and neuroradiologists who were not aware of the patients' identities and the random treatment assignments. 23 All study subjects were simultaneously scheduled for detailed neurological and neurocognitive function assessments at baseline (1-7 days after TAVR and before discharge) and at the 6-month follow-up. Neurological assessments included standard clinical scales of the National Institutes of Health Stroke Scale and the modified Rankin Scale, and neurocognitive function was assessed with the Montreal Cognitive Assessment, which was a recommended screening measure of global cognition and cognitive impairment.…”

Antithrombotic therapy in patients undergoing transcatheter aortic valve replacement (TAVR): from current evidence to perspective

“…In a 4D-CT analysis of the ATLANTIS study presented at American College of Cardiology 2021, HALT and RLM were lower with apixaban compared to with antiplatelets in patients without indication for OAC, but this was not associated with better clinical outcomes [43] . Low-dose rivaroxaban achieved similar results in the GALILEO 4D substudy [44] .…”