SCOPE I: Acurate Neo Comes Up Short for Severe Aortic Stenosis
Noninferiority with Sapien 3 at 30 days was not met, likely due to higher rates of PV leak and acute kidney injury for Acurate Neo.
SAN FRANCISCO, CA - In one of the first head-to-head comparisons of different TAVR devices, the investigational Acurate Neo (Boston Scientific) failed to meet a composite noninferiority endpoint in comparison with Sapien 3 (Edwards Lifesciences).
Jonas Lanz, MD (Bern University Hospital, Switzerland), reported the results here today at TCT 2019, with simultaneous publication in the Lancet.
Known as SCOPE I, this was the first randomized trial to compare the safety and efficacy of Acurate Neo to the US Food and Drug Administration-approved Sapien 3, Lanz observed during a morning press conference, noting that the device “is associated with favorable outcomes in nonrandomized studies.”
In their Lancet paper, Lanz and colleagues make the case for why head-to-head trials are needed even as TAVR has matured.
“As TAVR emerges as a valid treatment option for patients with severe, symptomatic aortic stenosis across all risk categories, high-quality studies comparing different TAVR devices are needed to provide sound evidence of the strengths and limitations of these devices, with the aim of optimizing device selection for individual patients,” they write. “The SCOPE I trial is one of the first studies to fill this important gap by reporting an early composite safety and efficacy endpoint to differentiate between devices.
From February 2017 to February 2019, a total of 739 patients at 20 European locations with severe, symptomatic aortic stenosis were randomized 1:1 to transfemoral TAVR with Acurate Neo (n = 372) or Sapien 3 (n = 367).
The primary endpoint was a combination of VARC-2 safety and clinical efficacy criteria at 30 days. These included all-cause death, any stroke, life-threatening or disabling bleeding, major vascular complications, coronary artery obstruction requiring intervention, acute kidney injury stage 2 or higher, valve-related dysfunction requiring repeat procedure, rehospitalization for valve-related symptoms or congestive heart failure, moderate or severe prosthetic valve regurgitation, or prosthetic valve stenosis at 30 days.
The composite primary endpoint occurred in 23.7% of patients treated with the Acurate Neo and in 16.5% of Sapien 3-treated patients, a more than 7% difference that meant the trial did not meet the prespecified criteria for noninferiority. In additional analyses addressing superiority, Sapien 3 emerged as superior to the investigational device.
While not powered for individual clinical endpoints, as Lanz noted during the formal presentation of results during a TCT late-breaking clinical trial session, specific endpoint analyses help illuminate why Acurate Neo may have fallen short. For example, there were more episodes of life-threatening bleeding for the Acurate Neo (n = 14) than for Sapien 3 (n = 9), as well as more cases of acute kidney injury (11 for Acurate Neo, 3 for Sapien 3).
Hard for Trials to Keep Pace
One ongoing challenge for these types of devices will be that TAVR technologies evolve faster than the pace of clinical trials, so that by the time results are reported the devices under review may be obsolete. Indeed, a new version of the Acurate Neo is already in clinical use in Europe. Still, the results are concerning for those who hoped that another TAVR device might be headed to the US market.
“It would be hard to make the clinical case, forget the regulatory case, for stating let’s use [Acurate Neo] if it performed like this relative to another choice,” Ajay Kirtane, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York), observed at the press conference.
Also speaking with the media, Mayra E. Guerrero, MD (Mayo Clinic, Rochester, MN), asked if a steep learning curve for using Acurate Neo may help to explain these disappointing findings, given that physicians do not have years of experience with the devices. Lanz responded that this was likely not a factor, since the mostly European clinicians involved in SCOPE I have had several years of access to this valve.
Acurate Neo has a self-expanding design, prompting questions during the press conference as to why the trial didn’t compare this new technology with a Medtronic self-expanding valve. In response, Lanz noted that such a trial, known as SCOPE II, is already underway in Europe, where the newer iteration of Acurate Neo is already on the market, with design changes aimed at reducing the risk of paravalvular leak. SCOPE I, in contrast, was specifically designed to compare the merits of balloon-expandable and self-expanding devices.
During the press conference Raj Makkar, MD (Cedars-Sinai Medical Center, Los Angeles, CA) noted that a US clinical trial of the device will use the next-generation Acurate Neo as well.
In the panel discussion following the formal presentation of results, panelists expressed confidence that the current shortcomings of Acurate Neo will be addressed in time. “To me it looks a bit like déjà vu, because we’ve seen this with the earlier valves and the development over time took care of these shortcomings,” observed Jeroen Bax, MD, PhD (Leiden University Medical Center, Leiden, the Netherlands). “I think if we understand a little bit better the potential anatomical features that are related to [the SCOPE I findings], then you can work with technological developments and move forward,” Bax concluded.
Session moderator Martin B. Leon, MD (NewYork-Presbyterian Hospital, New York, NY), concurred, stating, “The issues appear to be soluble.” Leon predicted that data from future clinical trials will prove more favorable to the Acurate Neo.
Lanz J, Kim W-K, Walther T, et al. Safety and efficacy of a self-expanding versus a balloon-expanding bioprosthesis for transcatheter aortic valve replacement in patients with symptomatic severe aortic stenosis: a randomized non-inferiority trial. Lancet. 2019;Epub ahead of print.
- Lanz reports no conflicts of interest.
- Boston Scientific funded the SCOPE I trial.