ILLUMENATE: Paclitaxel-Coated Balloon Outperforms PTA in Superficial Femoral Artery Disease

One-year results of the ILLUMENATE pivotal trial show that the investigational Stellarex™ drug-coated balloon (DCB) yields superior angiographic and clinical results compared with standard balloon angioplasty in a population with complex superficial femoral artery (SFA) disease.

“The ILLUMENATE pivotal trial met its 12-month primary safety and efficacy end points among one of the most complex patient populations studied in DCB investigational device exemption trials to date,” says co-principal investigator Sean Lyden, MD, who presented the findings at the recent Transcatheter Cardiovascular Therapeutics (TCT) conference in Washington, D.C.

“This trial builds on prior reports from the ILLUMENATE first-in-human and pharmacokinetics studies, the earlier ILLUMENTATE EU randomized trial and the ongoing ILLUMENATE global study,” adds Dr. Lyden, Chair of Cleveland Clinic’s Department of Vascular Surgery.

Trial design and points of distinction

The study involved 300 patients with SFA disease at 43 U.S. and European sites. Patients were randomized on a 2:1 basis to the Stellarex DCB with paclitaxel 2 μg/mm2 or to standard balloon percutaneous transluminal angioplasty (PTA).

Inclusion criteria included Rutherford class 2-4 disease, lesion location in the SFA and/or popliteal artery, at least one patent runoff vessel below the knee, and lesion length of 3 to 18 cm.

“Severe calcification, diabetes, chronic kidney disease, small vessels and use in women have been a challenge for current technologies for SFA disease,” Dr. Lyden observes, adding that this study was notable for large numbers of patients with severe calcification (43 percent) and diabetes (50 percent) and a large share of female patients (41 percent). He cites the calcification rates as especially noteworthy. “This trial was different from prior ILLUMENATE studies in that we had a much higher incidence of severe calcium.”

Outcomes were validated via blinded adjudication by independent angiographic and duplex ultrasound core laboratories and a clinical events committee.

Key results

The primary safety end point was a composite of freedom from device- and procedure-related death at 30 days and freedom from target limb major amputation and clinically driven target lesion revascularization at 12 months. This end point was met by 92.1 percent of DCB recipients versus 83.2 percent of PTA recipients (P < .001) (intent-to-treat analysis).

The primary efficacy end point was a composite of primary patency at 12 months, defined as freedom from target lesion restenosis (peak systolic velocity ratio ≤ 2.5 by duplex ultrasound), and freedom from clinically driven target lesion revascularization at 12 months. This end point was met by 76.3 percent of DCB recipients versus 57.6 percent of PTA recipients (P = .003) (intent-to-treat analysis).

Among other notable findings at 12 months:

• Primary patency was achieved in 82.3 percent of DCB recipients versus 70.9 percent of PTA recipients.
• Freedom from clinically driven target lesion revascularization was achieved in 93.6 percent of DCB recipients versus 87.3 percent of PTA recipients.
• Major adverse events occurred in 9.4 percent of DCB recipients versus 17.7 percent of PTA recipients and were driven primarily by target lesion revascularization events.
• All-cause mortality was slightly higher with DCB (2.6 percent) than with PTA (2.1 percent), but the difference was nonsignificant.

“Stellarex is a low-dose DCB that has demonstrated superiority in safety and efficacy over standard balloon angioplasty in one of the most complex patient groups studied in a DCB device trial,” Dr. Lyden notes.

In the wake of these 12-month results, Spectranetics Corporation submitted a regulatory application to the FDA for approval of the Stellarex DCB. Follow-up in the ILLUMENATE pivotal trial will continue through five years.