Transcatheter aortic valve implantation with the Trilogy valve for symptomatic native aortic regurgitation (ALIGN-AR): a pivotal, multicentre, single-arm, investigational device exemption study.
Document Type
Article
Publication Title
Lancet
Abstract
BACKGROUND: Transcatheter devices designed for calcific aortic stenosis are not optimised for use in native aortic regurgitation, and data on aortic regurgitation-dedicated platforms are limited. The extended ALIGN-AR pivotal experience with a prospectively enrolled continued-access cohort and longer follow-up aimed to characterise the safety, valve function, and clinical outcomes of transcatheter aortic valve intervention (TAVI) with a dedicated device in aortic regurgitation.
METHODS: ALIGN-AR is a prospective, multicentre, single-arm study enrolling patients at high surgical risk to undergo TAVI with a dedicated valve (Trilogy valve) for symptomatic moderate-to-severe or severe aortic regurgitation at 30 centres in the USA. Coprimary endpoints were a safety composite of major adverse events within 30 days post procedure (all-cause death, stroke, life-threatening or major bleeding, acute kidney injury, major vascular complications, need for additional surgical or percutaneous interventions, new pacemaker implantation, and moderate or greater aortic regurgitation), tested for non-inferiority against a margin of 1·35 applied to literature-based incidence of safety endpoint of 30% translating to performance goal of 40·5%, and 1-year all-cause mortality, tested for superiority against a performance goal of 25·0%. Analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov (NCT04415047), and is ongoing.
FINDINGS: Between June 8, 2018, and July 29, 2025, we screened 1352 patients and enrolled 700 patients (pivotal cohort n=180; continued access cohort n=520). Median age was 79·0 years (IQR 72·0-84·0), 321 (46%) were female, 379 (54%) were male, and 532 (76%) were White, 68 (10%) were Black or African American, and 36 (5%) were Asian. Technical success was achieved in 664 (95%) patients. The median duration of follow-up was 472 days (IQR 352-891). The 30-day primary safety composite endpoint occurred in 168 patients (24·0% [upper 97·5% CI 27·3%]; p
INTERPRETATION: In patients with symptomatic moderate-to-severe or severe aortic regurgitation considered to be of high surgical risk, TAVI with a dedicated platform met prespecified safety and effectiveness performance goals. We observed substantial reductions in aortic regurgitation, favourable valve haemodynamics and myocardial remodelling, with associated improvements in functional status and quality-of-life gains up to 2 years. These data support TAVI with a purpose-built device as a feasible and effective treatment option for selected patients with native aortic regurgitation who are at high risk for death or complications after surgery.
FUNDING: JenaValve Technology.
First Page
2757
Last Page
2771
DOI
10.1016/S0140-6736(25)02215-9
Publication Date
12-13-2025
Recommended Citation
Makkar RR, Thourani VH, Vahl TP, Yadav PK, McCabe JM, George I, Satler L, Chetcuti S, Daniels DV, Waggoner T, Whisenant B, Russo M, Summers M, Garcia S, Frisoli T, Ramana RK, Stinis C, Golwala H, Zahr F, Greenbaum A, Rovin J, Sanchez C, Szerlip M, Deeb GM, Amoroso N, Patel D, Fahy M, Ranard LS, Gupta A, Chakravarty T, Skaf S, Chuang M, Kodali SK, Figulla HR, Treede H, Baldus S, Pinto DS, Leon MB; ALIGN-AR Investigators. Transcatheter aortic valve implantation with the Trilogy valve for symptomatic native aortic regurgitation (ALIGN-AR): a pivotal, multicentre, single-arm, investigational device exemption study. Lancet. 2025 Dec 13;406(10521):2757-2771. doi: 10.1016/S0140-6736(25)02215-9. Epub 2025 Nov 16. PMID: 41260228.