Dissection is a frequent and clinically problematic outcome of percutaneous transluminal balloon angioplasty (PTA). There is no current safe and efficacious solution because revascularization of below-the-knee (BTK) arteries is dependent upon PTA, and there are no FDA-approved implants for use BTK. TOBA II BTK, a prospective, multicenter, single-arm global pivotal study, is the first investigational device exemption clinical trial approved to investigate safety and effectiveness of a permanent implant to repair dissections in BTK arteries. The study evaluated the Tack endovascular system (4 F) (Intact Vascular) in 233 patients who had ≥ 1 dissection requiring repair after PTA in the mid/distal popliteal, tibial, and/peroneal arteries. There were 918 Tacks implanted from the mid popliteal to 1 cm above the tibiotalar joint, with 122 placed in the distal third of the vessels.
The Tack system has four preloaded self-expanding nitinol implants on a single catheter. Each implant is 6 mm long and self sizes to vessels ranging from 1.5 to 4.5 mm in diameter, using sufficient radial force to appose dissected tissue against the vessel wall. Primary safety and efficacy endpoints were analyzed at 6 months and compared with performance goals derived from the critical limb ischemia (CLI) literature.
TOBA II BTK met both primary endpoints (P < .0001) of safety (30-day major adverse limb event or perioperative death) and efficacy (6-month major adverse limb event or 30-day perioperative death). All (100%) dissections were resolved following Tack implantation, with 92.0% 6-month Kaplan-Meier freedom from clinically driven target lesion revascularization (CD-TLR), 87.3% 6-month Kaplan-Meier target lesion patency, and 95.7% 6-month Kaplan-Meier amputation-free survival. Wounds were healed or improved in 73.8% and Rutherford category was ≤ 3 at 6 months in 74% of CLI patients.
TOBA II BTK met all endpoints in a 100% dissected vessel population. High rates of dissection resolution, wound improvement, and freedom from CD-TLR support the Tack endovascular system as an ideal adjunct to PTA and potentially as the first permanent vascular implant to improve results of infrapopliteal angioplasty.
5-Year ABSORB BTK Trial Results
Presenter: Ramon L. Varcoe, MBBS, MS, PhD
The ABSORB BTK trial is a prospective, nonrandomized, single-center study designed to evaluate a novel bioresorbable, drug-eluting scaffold used for the treatment of peripheral artery disease below the knee. There were 71 scaffolds utilized in 55 limbs of 48 patients who fulfilled the inclusion criteria (72.7% with critical limb ischemia). Most scaffolds were implanted in arteries of the proximal half of the calf, and the mean lesion length was 20.1 mm (range, 5–50 mm). There was 100% procedural and technical success.
Over the 5-year follow-up period, 38% of patients had died, all from causes unrelated to the procedure or study device; 95% of patients had sustained clinical improvement. Complete wound healing occurred in 90% of those treated for tissue loss, with no major amputations and a limb salvage rate of 100%. Primary patency (defined as freedom from peak systolic velocity ratio > 2.0 or target vessel occlusion) and freedom from clinically driven target lesion revascularization rates were estimated at 89.2%/80.3%/72.9% and 97.2%/90.7%/90.7% at 12, 36, and 60 months, respectively, using the Kaplan-Meier method. No late or very late scaffold thromboses were observed.
This novel bioresorbable, drug-eluting scaffold has several inherent advantages over stents, related to its biological resorption. These results represent best-in-class durability for a stent-like device in this challenging vascular territory.
Results of the LimFlow System in the PROMISE I Trial
Presenter: Daniel Clair, MD
The multicenter PROMISE I trial represents the first human use in the United States of a purpose-built percutaneous deep vein arterialization system for the treatment of no-option chronic limb-threatening ischemia (CLTI) patients. The LimFlow procedure permanently bypasses unreconstructible arteries and leverages healthier veins as a conduit to create new routes to perfuse tissue in the foot. The purpose of the PROMISE I trial is to establish the safety, effectiveness, and feasibility of the LimFlow system (LimFlow SA) for use in the treatment of CLTI.
Thirty-two no-option CLTI patients (mean age, 71 ± 14 years; 66% male) were enrolled in a nonrandomized manner at seven centers across the United States. All enrolled patients had Rutherford class 5 or 6 disease and were deemed by an independent review committee of experts to be ineligible for endovascular or surgical procedures to restore blood flow. Patients underwent percutaneous deep vein arterialization using the LimFlow system.
The primary safety endpoint was above-ankle amputation-free survival (AFS) at 30 days, with a secondary endpoint of AFS at 6 months. Other secondary endpoints included technical success, vessel patency, and wound healing.
The LimFlow procedure technical success rate was 97%, with only one technical failure. The primary safety endpoint of AFS at 30 days was 91%. The secondary endpoint of AFS at 6 months was achieved in 74%.
Initial 12-Month Outcomes From the TANGO Trial (Adventitial Temsirolimus in BTK Lesions)
Presenter: Ehrin Armstrong, MD
The TANGO trial is a phase 2, dose escalation, double-blinded trial comparing the delivery of temsirolimus to saline control in patients with severe claudication or critical limb ischemia. This is the first United States trial to investigate a sirolimus analog to improve the durability of peripheral revascularization procedures. The purpose of the trial is to limit neointimal hyperplastic tissue growth into the artery after endovascular below-the-knee (BTK) revascularization procedures, where paclitaxel-coated balloons have had limited success.
Results are now available comparing Bullfrog micro-infusion device (Mercator MedSystems) delivery of either low-dose temsirolimus treatment (0.1 mg/mL; n = 20) or saline control (n = 20) into the perivascular tissue around lesions subsequent to revascularization. Patients (Rutherford category 3–5) with up to 30-cm–long BTK lesions were enrolled in the study.
The primary safety endpoint was 30-day freedom from major adverse limb event or postoperative death, and no events were observed. The primary efficacy endpoint was improvement in 6-month transverse view vessel area loss (TVAL), an angiographic measure that uses the opacified area of the lesion to approximate the neointimal volume.
At 6 months, excluding subjects with unstented severe dissections in their target lesion, TVAL improved to 19% in treatment subjects compared to 38% in controls. With respect to secondary endpoints, 6-month freedom from target lesion failure was reported in 58% (11/19) of treatment subjects compared to 42% (8/19) of controls, favoring treatment by a relative 38%. In patients with total occlusions at baseline, 78% (7/9) of treatment subjects and 25% (2/8) of control subjects were free from reocclusion at 6 months. In treatment subjects with wounds upon enrollment or who developed wounds on their target limb during the study, 71% (5/7) of treatment subjects had full healing of wounds by 12 months without the need for clinically driven target lesion revascularization, whereas 44% (4/9) of control subjects had wound healing without prior clinically driven target lesion revascularization.
The ULYSSE Registry
Presenter: Costantino Del Giudice, MD
The Ulysse registry is a retrospective, nonrandomized, single-center study evaluating the safety and the efficacy of ultrasoundplasty before angioplasty to treat below-the-knee lesions (BTK) in 22 critical limb ischemia (CLI) patients (35 BTK lesions). All patients were Rutherford category 4 to 6 and had moderate-severe calcification. Ultrasoundplasty was performed using the Kapani catheter (Apani Corporation), which delivers a local, low-frequency, high-intensity ultrasound energy to the lesion.
The objective of the study was to demonstrate that locally delivered ultrasound energy may modify plaque structure using microcavitational effects and change plaque compliance without risk of vessel dissection and rupture. Modifications of plaque structure may potentially improve the outcome of a simple balloon angioplasty.
The primary safety outcomes were the major adverse events at 30 days, recurrence of CLI, and surgical or endovascular revascularization at 6 months. The primary efficacy endpoint was angiographic restenosis and target lesion revascularization at 6 months. Immediate outcomes showed good results, with 100% technical success and no major adverse events. At 6-month angiographic control, primary patency was 97.1%, with 100% ulcer healing and no target lesion revascularization and no CLI recurrence. At 24 months, freedom from restenosis was 91.4% as evaluated by Doppler ultrasound control, with no target lesion revascularization and no CLI recurrence. No major adverse events were reported.
Ultrasoundplasty before angioplasty for BTK lesions may improve clinical outcomes without the need for a drug-eluting device. A larger randomized study is needed to confirm these results.