First Round of Late-Breaking Clinical Trial Results Announced at VIVA19


VIVA Physicians, a not-for-profit organization dedicated to advancing the field of vascular medicine and intervention through education and research, announces the first round of 21 highly anticipated late-breaking clinical trial results at VIVA19 hosted at Wynn Las Vegas.

Below are highlights of this morning’s six late-breaking clinical trial presentations.

No Increased Long-Term All-Cause Mortality for the Paclitaxel-Coated Zilver PTX Drug-Eluting Stent Compared to Uncoated Devices
Presenter: Michael D. Dake, MD

Michael Dake, MD
Interventional Radiology
The University of Arizona Tucson, Arizona

The final long-term patient-level data for the Zilver PTX drug-eluting stent (DES) (Cook Medical) were evaluated to determine if there is an increased mortality risk due to paclitaxel. Because risk factors common in patients with peripheral artery disease may collectively contribute to patient prognosis, the contribution of baseline patient risk factors to mortality and freedom from target lesion revascularization (TLR) were also investigated.

Mortality through 5 years was compared for the primary randomization groups, which included 40% DES patients in the control group, as well as for the actual treatment groups. Actual treatment analysis compared patients treated with the DES to patients treated with nonpaclitaxel therapies. Imbalances in patient risk factors were considered. Mortality and freedom from TLR were evaluated for DES and percutaneous transluminal angioplasty (PTA)/bare-metal stent (BMS) risk factor groups.

Final 5-year mortality data were available for 94% of patients. The intent-to-treat mortality analysis comparing the DES primary randomization group to the PTA primary randomization group was not significant (P = .08). Despite randomization, combinations of risk factors were more prevalent in the DES primary randomization group compared to the PTA primary randomization group (P < .01); the numeric difference in mortality rates between groups may be due to the imbalance of risk factors at baseline. When stratified by number of risk factors, patients with fewer risk factors had a decreased mortality rate.

When comparing actual treatment groups, there was no difference in the 5-year mortality rates for the DES group compared to the PTA/BMS group (19.1% vs 17.1%; P = .60). When evaluating potential risk factors for freedom from TLR, the DES showed benefit across the different risk factor groups; a greater relative benefit was observed in groups with fewer risk factors. Analyses of the Zilver PTX DES demonstrated no increase in long-term mortality and support a benefit across different risk factor groups.

A Novel Sustained Limus Release Eluting Balloon: 2-Year Data From the SELUTION SFA Trial
Presenter: Thomas Zeller, MD, PhD

Thomas Zeller, MD, PhD
Freiburg Bad Krozingen, Germany

Historically, paclitaxel has been the drug of choice for use in drug-coated balloons (DCBs). The drawback of limus drugs compared with paclitaxel in DCBs has been the difficulty in transfer—because limus drugs have a relative lack of lipophilicity compared with paclitaxel, they have lower bioavailability when only short-term tissue contact is provided. The SELUTION SLR (MedAlliance) is based on microreservoir balloon coating technology, which provides controlled and sustained sirolimus release with a therapeutic effect for over 60 days. The cell adherent technology is a proprietary amphiphatic lipid technology that binds microreservoirs to the balloon surface, and it contains and protects microreservoirs during insertion and inflation. Also, it facilitates higher drug transfer efficiency, allowing for low drug dose (1 µg/mm2) on the balloon surface, and maximizes the drug bioavailability.

SELUTION SFA is a prospective, controlled, multicenter, open-label, single-arm clinical trial treating superficial femoral artery (SFA) lesions (lesion length, 51.3 ± 40.3 mm; 34% moderate-severe calcification). The trial enrolled 50 patients in four German centers between November 2016 and May 2017. Patients enrolled were symptomatic with de novo or restenotic lesions with ≥ 70% diameter stenosis or occlusion.

The primary endpoint was defined as late lumen loss (LLL) evaluated by angiography at 6 months. Duplex ultrasound and clinical endpoints were evaluated at 6, 12, and 24 months. Main secondary endpoints are primary patency, target lesion revascularization (TLR), change in Rutherford classification, and change in ankle-brachial index (ABI).

The SELUTION SFA trial met its primary endpoint and demonstrated an LLL of 0.19 mm. Excellent freedom from clinically driven TLR was achieved through 24 months in 87.5%, with no primary TLR event observed after month 11.

Clinical improvements were seen in Rutherford classification, ABI, and walking impairment at 6 months and were further improved to 12 months and maintained to 24 months. This initial first-in-human trial demonstrates that SELUTION SLR is a viable option to treat lesions in the SFA. It is the first demonstration of a sirolimus safety and efficacy in peripheral intervention.

RANGER II SFA: Randomized Trial of RANGER DCB Versus PTA in the SFA
Presenter: Ravish Sachar, MD

Ravish Sachar, MD
Interventional Cardiology UNC-REX Raleigh, North Carolina

The global RANGER II SFA randomized (3:1) study compared treatment with the Ranger drug-coated balloon (DCB; paclitaxel dose density, 2 µg/mm2) (Boston Scientific Corporation) with standard percutaneous transluminal angioplasty (PTA) in the femoropopliteal segment. Baseline characteristics were similar between the Ranger DCB (n = 278, 37.8% women, 42.4% with diabetes) and standard PTA control groups (n = 98, 31.6% women, 43.9% with diabetes). Mean lesion length was 82.5 ± 48.9 mm for the Ranger DCB group and 79.9 ± 49.3 mm for the control group. The first 306 patients to complete 12-month follow-up were included in the primary endpoint analysis according to the prespecified interim analysis plan. Follow-up is ongoing for the remaining patients.

Ranger DCB met the study endpoint criterion for superior effectiveness at 12 months with primary patency of 82.0% vs 68.8% for PTA (P = .013) and demonstrated noninferior safety with a major adverse event–free rate of 93.5% vs 82.1% (noninferiority P < .0001). The Kaplan-Meier estimate of primary patency was 89.2% at 12 months for Ranger DCB vs 72.9% for PTA (log rank P = .002). The target lesion revascularization rate was significantly lower in the Ranger DCB group as compared with the PTA group (6.0% vs 17.9%; P = .002). There was no difference in all-cause death between groups (2.3% vs 2.5%; P > .99).

In this primary endpoint analysis of interim data, the low-dose Ranger DCB demonstrated primary patency superior to standard PTA through 1 year, with fewer reinterventions and a good safety profile.

4-Year Outcomes From the IN.PACT Global Study
Presenter: Thomas Zeller, MD, PhD

The IN.PACT Global Study is a prospective, multicenter, single-arm study conducted at 64 international sites. Patients with complex lesions were enrolled, including bilateral disease, multiple lesions, TASC A through D, de novo, in-stent restenosis, long lesions, and chronic total occlusions. The 1,406 intent-to-treat patients (1,773 lesions) were treated with the In.Pact Admiral drug-coated balloon (DCB) (Medtronic) and analyzed as a part of the consecutively enrolled clinical cohort, with safety and revascularization events reviewed by an independent clinical events committee.

Assessments through 48 months were freedom from clinically driven target lesion revascularization (CD-TLR) and the safety endpoint, which was a composite of freedom from device- and procedure-related mortality through 30 days, freedom from major target limb amputation, and clinically driven target vessel revascularization through 48 months after the index procedure.

The mean patient age in the clinical cohort was 68.6 ± 10.1 years, and 67.8% were male. The mean lesion length was 12.09 ± 9.54 cm, including 18% in-stent restenosis, 35.5% total occlusions, and 68.7% calcified lesions. The Kaplan-Meier estimate of freedom from CD-TLR through 48 months was 73.4%. The cumulative incidence of the safety composite endpoint was 71.9%, with a low major target limb amputation rate (1.1%) through 48 months. The Kaplan-Meier estimate of freedom from all-cause death through 48 months was 83.5%. In an additional analysis, the Kaplan-Meier estimate of freedom from CD-TLR was 74.5% for claudicants and 64.8% for critical limb ischemia (CLI) patients.

Results from this real-world study demonstrate long-term, sustained clinical benefit and safety with low amputation and mortality rates in patients treated with the In.Pact Admiral DCB. Furthermore, the results demonstrate long-term effectiveness in claudicants and CLI patients through 4 years and support the use of a DCB for the treatment of femoropopliteal disease.

DCB Versus POBA After B-Laser Atherectomy
Presenter: John H. Rundback, MD

John Rundback, MD
Interventional Radiology
Interventional Institute,
Holy Name Medical Center
Teaneck, New Jersey

The B-Laser (AngioDynamics/Eximo Medical) represents a new atherectomy device utilizing a 355-nm laser with a very short pulse width to selectively ablate mixed-morphology plaque including calcification. Outcomes were compared for patients treated in the European Union CE Mark and United States investigational device exemption studies with B-Laser, followed by either plain old balloon angioplasty (POBA; n = 46) or drug-coated balloon (DCB) angioplasty (n = 51).

Clinical characteristics were similar between the two groups. POBA patients had more popliteal and tibial lesions treated (77.8% and 84.2% vs 11.1% and 15.8% in the DCB group), but other lesion characteristics were similar. There were no major procedural complications, including no embolization and no grade C–E dissections. Core lab–adjudicated duplex patency at 6 months was 89.5% in the POBA group and 85.2% in the DCB group. One-year clinical improvement (ankle-brachial index, Rutherford score) were the same.

These preliminary data indicate no differences in measurable short-term outcomes following B-Laser atherectomy regardless of subsequent mode of angioplasty. The characteristics of plaque modification following B-Laser atherectomy may impact outcomes and mitigate previously noted patency and clinical benefits of DCB angioplasty.

Two-Year Outcomes From the IMPERIAL Randomized Trial of Eluvia and Zilver PTX
Presenter: Osamu Iida, MD, on behalf of the IMPERIAL investigators

Osamu Iida, MD
Interventional Cardiology
Kansai Rosai Hospital Amagasaki, Japan

The global IMPERIAL randomized controlled trial (N = 465) was designed to compare performance of the Eluvia paclitaxel-eluting nitinol stent (Boston Scientific Corporation) with the Zilver PTX paclitaxel-coated stent (Cook Medical) for treatment of femoropopliteal artery lesions.

Multiple challenging lesion and disease characteristics were represented in the study, with mean lesion lengths of 86.5 ± 36.9 mm and 81.8 ± 37.3 mm for Eluvia and Zilver PTX groups, respectively; 42% and 44% had diabetes, and 31% and 30% had occlusions, respectively.

At 24 months, the Kaplan-Meier estimates of primary patency were 83% and 77.1% for patients treated with Eluvia and Zilver PTX, respectively (log-rank P = .10). The clinically driven target lesion revascularization rate was significantly less for patients treated with Eluvia (12.7% vs 20.1%; P = .0495).

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