Christian Spaulding presented the background and study design of the NEVO RES-I trial at EuroPCR. The Nevo sirolimus-eluting coronary stent (Cordis) is the first drug-eluting stent utilising RES Technology, a reservoir technology that incorporates hundreds of small reservoirs, each acting as a depot into which drug-polymer compositions are loaded.
The design allows drug delivery from a stent with a surface that is 75% bare metal upon insertion and becomes a simple bare metal in approximately three months following drug delivery and polymer bioresorption.
NEVO RES-I is a randomised comparison of Nevo to the Taxus-Liberté stent (Boston Scientific) in de novo native coronary artery lesions. The primary endpoint is angiographic in-stent late lumen loss at six months. Key secondary endpoints included target lesion failure, target vessel failure, major adverse cardiac events (MACE), stent thrombosis, target lesion revascularisation (TLR), target vessel revascularisation (TVR), and angiographic in-stent and in-segment binary restenosis at six months. A subset of patients was evaluated via intravascular ultrasound at six months.
“In this trial, Nevo was superior to Taxus Liberté in a number of key safety and efficacy measures, including the primary endpoint of late lumen loss,” said Spaulding, Professor of Cardiology, Assistance Publique-Paris Decartes University Hospitals, Paris, France and one of the primary investigators of the trial. “We also saw an emerging safety profile with Nevo that adds to our enthusiasm about the potential of this drug-eluting stent for patients with coronary artery disease.”
The study enrolled 394 patients at 40 sites throughout Europe, South America, Australia and New Zealand. Clinical follow-up was planned at 30 days and six months, and will be completed annually through five years.
Nevo had significantly lower in-stent late lumen loss. Specifically, late lumen loss was reduced by 64% in the Nevo arm as compared with the Taxus-Liberté arm (0.13mm compared with 0.36mm, p<0.001).
In addition, Nevo also showed superior angiographic results to Taxus-Liberté in reducing restenosis at six months. Angiographic restenosis was reduced 86% (1.1% in the Nevo arm compared with 8.0% in the Taxus-Liberté arm, p<0.002).
Nevo also reduced the incidence of MACE by more than 40% compared with Taxus (4.1% vs. 7.0%, respectively, p=0.226). MACE events occurring between hospital discharge and six months were reduced 67% from 4.8% with Taxus to 1.6% with Nevo (p=0.08).
NEVO RES I was not designed to show differences in clinical outcomes, however, patients treated with Nevo had numerically lower rates of events with respect to TLR (1.6% for Nevo vs. 3.2% for Taxus-Liberté, p=0.33) and the composite of death or heart attack (2.6% vs. 4. 3%, respectively, p=0.26) compared with patients receiving Taxus.
Based on the Academic Research Consortium’s definitions of stent thrombosis, there were no reports of stent thrombosis in the 202 patients receiving Nevo while there were two reports in the 192 patients receiving the Taxus-Liberté stent, both of whom were on dual antiplatelet therapy at the time.
Results in diabetic patients
In the NEVO RES-I study, a similar magnitude of benefit of the Nevo stent over the Taxus Liberte stent was seen in patients with diabetes as in patients without diabetes.
In a pre-specified subset analysis of the 65 patients with diabetes completing six-month follow-up, there was a 60% reduction in in-stent late lumen loss with Nevo versus Taxus Liberte (0.17mm compared to 0.42mm, p<0.03). The magnitude of the differences seen in favour of Nevo was similar to the 65% reduction seen in 277 non-diabetic patients (0.12mm, compared to 0.34mm in the Taxus Liberte arm, p<0.001).
Nevo is made of cobalt chromium, which makes the stent flexible and conformable with thin struts to maximise vessel coverage. The biodegradable polymer used to contain and release sirolimus facilitates rapid endothelialisation and results of pre-clinical studies indicated no greater inflammation than seen with bare metal stents.
Nevo also contains the same drug, sirolimus, as the Cypher stent, which has now been used in more than three million people worldwide. Data supporting the safety and efficacy of sirolimus in coronary applications is now available out to six years, and this body of clinical evidence is completely unmatched by any other anti-restenotic stent.
Upcoming studies
Cordis announced additional upcoming clinical trials for Nevo at EuroPCR:
NEVO II will be a randomised, non-inferiority trial comparing Nevo to Xience V. The study plans to enrol several thousand patients with coronary artery disease and will include expanded enrolment in multiple patient subgroups. The primary endpoint is target lesion failure at 12 months. Results will provide long-term data in support of a pre-market approval application with the FDA.
NEVO III will be a non-randomised, single-arm trial evaluating clinical outcomes in approximately 1,200 patients throughout the US and Canada. The primary endpoint will be target lesion failure at 12 months. The study will be led by Dan Simon, Case Western Reserve University School of Medicine, Cleveland, and David Kandzari, Scripps Clinic, San Diego.
The Cypher Stent/DAPT (dual antiplatelet therapy) trial will compare Nevo with a Cypher stent control arm. The study will enrol 2,000 patients and compare clinical outcomes in a broad range of patients receiving DAPT for 12 months vs. 30 months after receiving a Cypher stent. This trial will contribute to the company’s involvement in a broader DAPT clinical programme, required by the FDA, which involves all FDA-approved drug-eluting stents.
