Positive results from the ALIGN AR pivotal trial, investigating the use of the Trilogy (JenaValve) transcatheter aortic valve implantation (TAVI) system in high-risk patients with symptomatic, severe aortic regurgitation, were presented during a late-breaking clinical trial session at TCT 2023 (23–26 October, San Francisco, USA).
Vinod Thourani (Piedmont Heart Institute, Atlanta, USA), who presented the results of the study, said that the device is “well positioned to become the preferred therapy” for patients with moderate to severe or severe aortic regurgitation who may be at high risk for surgery.
Untreated, severe, symptomatic aortic regurgitation is associated with high mortality, Thourani explained in his presentation, adding that while surgery remains only recommended in patients with native severe aortic regurgitation, there are a multitude of high risk patients who are not offered therapy.
The self-expanding Trilogy valve is the first TAVI system designed to address this patient population, for whom treatment options are currently limited. The Trilogy valve features locators that clip onto native leaflets and enable secure anchoring in the absence of calcium, as well as large-open cells that are designed to facilitate future coronary access.
ALIGN AR, which enrolled a total of 180 patients at 20 sites, is a landmark prospective, single-arm investigation device exemption (IDE) study designed to assess the safety and efficacy of the Trilogy system within high-risk patients with symptomatic aortic regurgitation and is intended to support a premarket approval submission to the US Food and Drug Administration (FDA). Clinical evaluation, echocardiography, functional and quality of life assessments are scheduled at 30 days, six months, one year and annually up to five years.
On safety—assessed against a composite of 30-day all-cause mortality, stroke, life-threatening or major bleeding, major vascular complications, acute kidney injury (AKI), valve intervention, new permanent pacemaker or moderate or greater paravlavular regurgitation (PVR)—Thourani reported that the valve met the non-inferiority criteria needed to achieve its primary endpoint, with a rate of 26.7% recorded against a prespecified non-inferiority margin of 40.5%.
Simarly, the efficacy of the device—which was measured by the rate of all-cause mortality at one-year—also came in favourably, with a rate of 7.8% reported by investigators, compared against a 25% prespecified non-inferiority margin.
Thourani also reported the rate of new pacemaker implantations seen throughout the trial, divided into the first, second and third group of 60 patients enrolled, which stood at 30%, 28% and 14% respectively. He attributed this improvement toward the later stage of the trial as likely being due to the insertion technique, placing locators above the nadir of the native valve cusp, a reduction in oversizing, and also evolution in the management of periprocedural conduction abnormalities.
Alongside these findings, Thourani noted that there were further positive indicators of the valve’s performance, with large effective orifice area (EOA) and low transvalvular gradients, as well as low paravalvular regurgitation at one year. In addition, echocardiography demonstrated improvements in left ventricular remodelling, and patients reported sustained improvement in quality of life and heart failure functional status through to one year.
“In a population of symptomatic patients with moderate to severe, or severe aortic regurgitation at higher surgical risk, TAVI using the Trilogy THV [transcatheter heart valve] achieved safety outcomes that met the 30-day performance goal, achieved an efficacy outcome of all-cause mortality that met the 12-month performance goal and among safety endpoints the rate of new pacemaker implantation was 24% and declined during the course of the trial due to changes in implant technique and oversize strategy,” Thourani said in his concluding remarks. “The Trilogy THV performance was excellent, with a large EOA and low transvalvular gradients. There was 0 moderate or greater than moderate PVR at one year and echocardiography demonstrated significant improvement in LV remodelling.”
