The PARADIGM pivotal trial will randomize approximately 1,000 “all-comer” patients with severe calcific aortic stenosis 1:1 to the DurAVR transcatheter heart valve versus currently approved TAVR devices. The primary endpoint is a one-year noninferiority composite of all-cause mortality, all stroke, and cardiovascular hospitalization. Danish sites are slated to open in Q4 2025.
Anteris has secured regulatory clearance from the Danish Medicines Agency to initiate PARADIGM, positioning Denmark as the first activation point in a planned global program spanning the United States, Europe, and Canada. An Investigational Device Exemption is under FDA review, with U.S. site initiation expected after approval and IRB clearances. The company is targeting approvals in both the U.S. (PMA) and EU (CE Mark) with a head-to-head randomized design intended to meet current evidentiary expectations under MDR and FDA’s preference for comparative data in a crowded, mature category.
Strategically, Anteris is entering the most competitive corner of structural heart with a direct comparison against entrenched TAVR platforms. The trial’s all-risk, all-comer positioning signals a bid for a broad initial label, not a niche foot-in-the-door. Opting for a noninferiority primary endpoint is pragmatic against well-characterized incumbents; the differentiation thesis rests on secondary measures and longer-term performance. DurAVR’s biomimetic leaflet geometry and single-piece ADAPT tissue are being framed around physiologic flow and anti-calcification potential—attributes aimed at durability, gradients, and leaflet function where market leaders face ongoing scrutiny, especially as TAVR usage expands into younger, lower-risk cohorts. A pivotal, randomized head-to-head design also serves as a counter to device iteration skepticism, where regulators increasingly want proof that new tissue and delivery innovations translate into clinical gains.
The implications for trial execution are significant. Cath labs will need to balance randomization with established device preferences, which can slow screening and increase consent friction. Training and proctoring for the ComASUR balloon-expandable delivery system, inventory planning for both investigational and control devices, and robust imaging oversight (echo and CT core labs) will add operational weight. CROs and vendors should expect complex multi-region start-up sequencing, with Denmark anchoring early enrollment while U.S. timelines hinge on the IDE decision. For sites, the appeal is participation in a rare, adequately powered head-to-head TAVR trial, but the operational reality includes device crossover policies, standardized antithrombotic regimens, and tight adjudication of conduction disturbances, pacemaker implantation, paravalvular leak, leaflet thickening, and valve thrombosis—signals that will determine whether “noninferior” becomes “clinically preferred.” Regulators and payers will focus beyond the composite endpoint on gradients, effective orifice area, rehospitalization drivers, and the early durability curve, particularly if the program includes adjunct cohorts outside the main randomized population.
The near-term watchlist is straightforward: timing of FDA IDE approval, first-patient-in milestones in Denmark and subsequent EU/Canada sites, and publication of detailed secondary endpoints and monitoring plans. Any interim analyses, adaptive features, or imaging substudies will be important indicators of how the program plans to demonstrate differentiation. On the risk side, enrollment velocity in a market dominated by familiar devices, the stringency of noninferiority margins, and any mid-study device iterations could challenge timelines and interpretability. Execution will also depend on manufacturing scale and consistency of the ADAPT tissue supply chain. If PARADIGM can pair noninferiority on hard events with clear advantages in hemodynamics, conduction safety, and early durability, Anteris will have a credible regulatory and commercial path. If not, the bar for displacing incumbent TAVR choices remains high.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
