One-year follow-up after active aortic aneurysm sac treatment with shape memory polymer devices during endovascular aneurysm repair.

OBJECTIVE: To determine the safety and efficacy of treating abdominal aortic aneurysm (AAA) sacs with polyurethane shape memory polymer (SMP) devices during endovascular aneurysm repair (EVAR), using a technique to fully treat the target lumen after endograft placement (aortic flow volume minus the endograft volume). SMP devices self-expand in the sac to form a porous scaffold that supports thrombosis throughout its structure. METHODS: Two identical prospective, multicenter, single-arm studies were conducted in New Zealand and the Netherlands. The study population was adult candidates for elective EVAR of an infrarenal AAA (diameter of ≥55 mm in men and ≥50 mm in women). Key exclusion criteria were an inability to adequately seal a common iliac artery aneurysm, patent sac feeding vessels of >4 mm, and a target lumen volume of <20 mL or >135 mL. Target lumen volumes were estimated by subtracting endograft volumes from preprocedural imaging-based flow lumen volumes. SMP devices were delivered immediately after endograft deployment via a 6F sheath jailed in a bowed position in the sac. The primary efficacy end point was technical success, defined as filling the actual target lumen volume with fully expanded SMP at the completion of the procedure. Secondary efficacy outcome measures during follow-up were the change in sac volume and diameter, rate of type II endoleak and type I or III endoleaks, and the rate of open repair and related reinterventions, with data collection at 30 days, 6 months, and 1 year (to date). Baseline sac volumes and diameters for change in sac size analyses were determined from 30-day imaging studies. Baseline and follow-up volumes were normalized by subtraction of the endograft volume. RESULTS: Of 34 patients treated with SMP devices and followed per protocol, 33 patients were evaluable at 1 year. Preprocedural aneurysm volume was 181.4 mL (95% confidence interval [CI], 150.7-212.1 mL) and preprocedural aneurysm diameter was 60.8 mm (95% CI, 57.8-63.9 mm). The target lumen volume was 56.3 mL (95% CI, 46.9-65.8 mL). Technical success was 100% and the ratio of SMP fully expanded volume to estimated target lumen volume was 1.4 ± 0.3. Baseline normalized sac volume and diameter were 140.7 mL (95% CI, 126.6-154.9 mL) and 61.0 mm (95% CI, 59.7-62.3 mm). The adjusted mean percentage change in normalized volume at 1 year was -28.8% (95% CI, -35.3 to -22.3%; P < .001). The adjusted mean change in sac diameter at 1 year was -5.9 mm (95% CI, -7.5 to -4.4 mm; P < .001). At 1 year, 81.8% of patients (95% CI, 64.5%-93.0%) achieved a ≥10% decrease in normalized volume and 57.6% of patients (95% CI, 39.2%-74.5%) achieved a ≥5 mm decrease in diameter. No device- or study procedure-related major adverse events occurred through 1 year after the procedure. CONCLUSIONS: Treatment of AAA sacs with SMP devices during EVAR resulted in significant sac volume and diameter regression at 1 year with an acceptable safety profile in this prospective study.

A Cost-Consequence Analysis Comparing Balloon-Expandable Covered Stents for the Management of Aortoiliac Occlusive Disease.

PURPOSE: To compare procedural and long-term costs associated with the use of Balloon-Expandable Covered Stents (BECS) in the management of Aortoiliac Occlusive Disease (AIOD). MATERIALS AND METHODS: A cost-consequence model was developed to simulate the intra- and post-operative management of patients with AIOD from the perspective of private health-payers. The study assessed the costs of the LifeStream (BD, Franklin Lakes, New Jersey), iCAST/Advanta V12 (Getinge, Goteborg, Sweden), BeGraft Peripheral (Bentley, Hechingen, Germany), and Viabahn Balloon Expandable (VBX) (W.L. Gore, Flagstaff, Arizona) BECS devices. Device costs were identified from the Australian Prosthesis List, whereas clinical outcomes of BECS were estimated from a systematic review of the literature. Costs were calculated over 24 and 36 month time horizons and reported in US dollars. RESULTS: Long-term, per-patient cost of each device at 24 and 36 months was $6253/$6634 for the LifeStream; $6359/$6869 for the iCAST/Advanta V12; $4806 (data available to 24 months) for the BeGraft Peripheral; and $4839/$5046 for the Viabahn VBX, respectively. Most of the cost difference was attributed to the number of stents required per treated limb and frequency of clinically-driven target lesion revascularization events. CONCLUSIONS: Best-available clinical evidence and economic modeling demonstrates that the BeGraft Peripheral and Viabahn VBX were of similar cost and the least costly options at 24 months, whereas at 36 months, the lowest cost BECS option for the treatment of AIOD was the Viabahn VBX. CLINICAL IMPACT: This analysis supports economically informed decision-making for health-payers managing systems that care for patients with AIOD. Stent length and avoiding reintervention were identified as key areas of cost-saving for future BECS development.

Imageable Radioembolization Microspheres for Treatment of Unresectable Hepatocellular Carcinoma: Interim Results from a First-in-Human Trial.

PURPOSE: To determine 6-month interim safety, effectiveness, and multimodal imageability of imageable glass microsphere yttrium-90 (90Y) radioembolization for unresectable hepatocellular carcinoma (HCC) in a first-in-human trial. MATERIALS AND METHODS: Imageable microspheres (Eye90 Microspheres; ABK Biomedical, Halifax, Nova Scotia, Canada), a U.S. Food and Drug Administration (FDA) Breakthrough-Designated Device consisting of glass radiopaque 90Y microspheres visible on computed tomography (CT) and single photon emission CT (SPECT), were used to treat 6 subjects with unresectable HCC. Patients underwent selective (≤2 segments) treatment in a prospective open-label pilot trial. Key inclusion criteria included liver-only HCC, performance status ≤1, total lesion diameter ≤9 cm, and Child-Pugh A status. Prospective partition dosimetry was utilized. Safety (measured by Common Terminology Criteria for Adverse Events [CTCAE] v5), multimodal imageability on CT and SPECT, and 3- and 6-month imaging response by modified Response Evaluation Criteria in Solid Tumors on magnetic resonance (MR) imaging were evaluated. RESULTS: Seven tumors in 6 subjects were treated and followed to 180 days. Administration success was 100%. Microsphere distribution measured by radiopacity on CT correlated with SPECT. Ninety-day target lesion complete response (CR) was observed in 3 of 6 subjects (50%) and partial response (PR) in 2 (33.3%). At 180 days, target lesion CR was maintained in 3 subjects (50%) and PR in 1 (16.7%). Two subjects could not be reassessed, having undergone intervening chemoembolization. All subjects reported adverse events (AEs), and 5 reported AEs related to treatment. There were no treatment-related Grade ≥3 AEs. CONCLUSIONS: Radioembolization using imageable microspheres was safe and effective in 6 subjects with unresectable HCC at 6-month interim analysis. Microsphere distribution by radiopacity on CT correlated with radioactivity distribution by SPECT, providing previously unavailable CT-based tumor targeting information.

Stellarex Drug-Coated Balloon for the Treatment of Peripheral Artery Disease: Five-Year Results from the ILLUMENATE Pivotal Randomized Controlled Trial.

This study aimed to report the 5-year outcomes from the ILLUMENATE Pivotal randomized controlled trial of the lower dose (2 µg/mm2) Stellarex drug-coated balloon (DCB) (Philips, formerly Spectranetics Corp, Colorado Springs, Colorado) compared with percutaneous transluminal angioplasty (PTA) for the treatment of symptomatic peripheral arterial disease. Long-term safety and effectiveness data for DCBs remains limited. The ILLUMENATE Pivotal was a prospective, randomized, multi-center, single-blinded study. Patients (Rutherford Clinical Category 2 to 4) were randomized 2:1 to Stellarex DCB or PTA. Follow-up was through 60 months. In total, 300 patients were enrolled. The mean age was 68.8 ± 10.2 years. At 60 months, freedom from a primary safety event was 69.2% in the Stellarex DCB arm and 68.2% in the PTA arm (log-rank, p = 0.623). The cumulative rate of major adverse events was 41.0% compared with 44.6% (p = 0.597), respectively. Freedom from clinically-driven target lesion revascularization (CD-TLR) was 70.3% in the Stellarex DCB arm compared with 68.2% in the PTA arm (p = 0.505). Time to first CD-TLR was 768.3 ± 478.9 days compared with 613.5 ± 453.4 days, respectively (p = 0.161). Kaplan-Meier estimates of freedom from all-cause mortality were 80.1% in the Stellarex DCB arm and 80.2% in the PTA arm (log-rank, p = 0.980). In conclusion, the 5-year results of the ILLUMENATE Pivotal randomized controlled trial add to the consistent safety data from the broader ILLUMENATE clinical program. These are the first data to report the 5-year safety and efficacy of a lower dose (2 µg/mm2) DCB for the treatment of symptomatic peripheral arterial disease. Clinicaltrials.gov Registration:NCT01858428.

Five-Year Independent Patient-Level Mortality Analysis of the Pooled ILLUMENATE Pivotal and EU Randomized Controlled Trials.

Background: There is a need to evaluate the latest information regarding a potential late safety signal in patients treated with paclitaxel-coated devices for peripheral artery disease. We evaluated the 5-year all-cause mortality rate of the Stellarex drug-coated balloon (DCB) compared with percutaneous transluminal angioplasty (PTA). Methods: An independent third-party performed a patient-level meta-analysis of the pooled ILLUMENATE Pivotal and EU randomized controlled trials. The primary outcome was time to death. Kaplan-Meier estimates of all-cause mortality were compared with the log-rank test. Predictors of mortality were assessed with Cox proportional hazard modeling. A blinded clinical events committee adjudicated all serious adverse events (including death). The follow-up was 60 months. Results: A total of 589 patients were followed for a median of 4.9 years (IQR, 4.8, 5.1 years); 419 were randomized to Stellarex DCB and 170 to PTA. Vital status was obtained for 93.8%. The 5-year Kaplan-Meier estimates of freedom from all-cause death were 80.4% (95% CI, 76.7%-84.3%) in the Stellarex DCB arm versus 80.4% (95% CI, 74.3%-86.5%) in the PTA arm (log-rank, P = .7754). There was no difference in all-cause mortality when stratified by paclitaxel dose terciles. Predictors of mortality included renal insufficiency, reference vessel diameter, age, and lesion length, but not paclitaxel dose nor paclitaxel exposure. Conclusions: There was no difference in all-cause mortality between the Stellarex DCB and PTA through the final 5-year follow-up window of 2 ILLUMENATE randomized controlled trials. These long-term data build on the previously reported safety of the Stellarex DCB for treating symptomatic femoropopliteal peripheral artery disease.

Evaluation of an Infrapopliteal Drug-Eluting Resorbable Scaffold: Design Methodology for the LIFE-BTK Randomized Controlled Trial.

Background: Critical limb-threatening ischemia (CLTI) is a severe condition characterized by rest pain and ischemic tissue loss that affects 5% to 10% of people with peripheral artery disease. In the United States, there are few Food and Drug Administration-approved devices for the primary treatment of arteries below-the-knee (BTK). Unfortunately, all suffer from high restenosis rates due to intimal hyperplasia, elastic recoil, and untreated dissection because of a lack of scaffolding. The Esprit BTK system is a resorbable, drug-eluting scaffold device with the potential to address an unmet need in people suffering from CLTI because of infrapopliteal atherosclerosis. The LIFE-BTK (pivotaL Investigation of saFety and Efficacy of drug-eluting resorbable scaffold treatment-Below The Knee) randomized controlled trial (RCT) is a prospectively designed premarket evaluation of the Esprit BTK drug-eluting resorbable scaffold used in the treatment of those patients. Methods: The LIFE-BTK trial enrolled 261 subjects with CLTI for the RCT and a further 7 subjects for a pharmacokinetic substudy. The objective of the RCT was to evaluate the safety and efficacy of the Esprit BTK scaffold compared to percutaneous transluminal angioplasty. The primary efficacy end point was a composite of limb salvage and primary patency at 12 months. The primary safety end point is freedom from major adverse limb events and peri-operative death at 6 months and 30 days, respectively. Clinical follow-up care is planned for 5 years. Conclusions: Novel devices must be tested in RCTs to evaluate their safety and efficacy compared to the standard of care if we are to improve outcomes for this challenging group of patients.

Intravascular Lithotripsy for Peripheral Artery Calcification: Mid-term Outcomes From the Randomized Disrupt PAD III Trial.

Background: Endovascular treatment of calcified peripheral artery lesions may be associated with suboptimal vessel expansion, increased complication risk, and reduced long-term patency. The primary endpoint from the Disrupt PAD III randomized controlled trial (RCT) demonstrated superior procedural success in patients treated with intravascular lithotripsy (IVL) vs percutaneous transluminal angioplasty (PTA). The present study evaluates primary patency after 1 and 2 years in this randomized population. Methods: The Disrupt PAD III RCT enrolled 306 patients with moderately-to-severely calcified femoropopliteal arteries treated with IVL (n = 153) or PTA (n = 153) prior to DCB treatment or stenting. The powered secondary effectiveness endpoint was primary patency at 1 year, defined as freedom from clinically driven target lesion revascularization plus freedom from restenosis determined by duplex ultrasound. Acute PTA failure requiring stent placement during the index procedure was prespecified as a loss of primary patency. Results: Primary patency at 1 year was significantly greater in the IVL arm (80.5% vs 68.0%, P = .017). The requirement for provisional stenting was significantly lower in the IVL group (4.6% vs 18.3%, P < .0001). Freedom from clinically driven target lesion revascularization (IVL: 95.7% vs PTA: 98.3%, P = .94) and restenosis rates (IVL: 90.0% vs PTA: 88.8%, P = .48) were similar between the 2 groups at 1 year. At 2 years, primary patency remained significantly greater in the IVL arm (70.3% vs 51.3%, P = .003). Conclusions: The Disrupt PAD III RCT secondary endpoint of superior 1-year primary patency was achieved, confirming the consistent safety and effectiveness of IVL followed by DCB treatment to facilitate a durable approach for patients with heavily calcified femoropopliteal arteries largely without stent requirement.