Primary Effectiveness Endpoint Research Articles

How safe and effective are flow diverters for the treatment of unruptured small/medium intracranial aneurysms of the internal carotid artery? Meta-analysis for evidence-based performance goals

BackgroundThe objective of this meta-analysis was to establish safety and effectiveness benchmarks for endovascular therapy of unruptured small-to-medium internal carotid artery (ICA) aneurysms using flow diverters.MethodsA systematic literature review and...

Lessons from "real life experience" of rifaximin use in the management of recurrent hepatic encephalopathy.

BACKGROUNDHepatic encephalopathy (HE) is a major complication of cirrhosis with independent prognostic significance. The current management of HE is mainly based on lactulose. Rifaximin has been shown to decrease the risk of HE recurrence in patients with episodic forms. HE can also be persistent. However, there is no drug support recommendation for rifaximin use in this setting.AIMTo assess the effectiveness of rifaximin in the management of recurrent episodes of HE and recurrent acute exacerbations on persistent HE, in “real life conditions”.METHODSIn this retrospective study, using a within-subjects design, we collected data of patients treated with rifaximin for HE in two liver diseases centers, during the six-month period before and during the six-month period after the initiation of rifaximin. The primary effectiveness endpoint was the total number of HE events involving hospitalization.RESULTSRifaximin was introduced for prevention of recurrent HE episodes in 29 out of 62 patients with normal mental status between episodes and for prevention of recurrent acute exacerbations on persistent HE in 33 out of 62 patients. In the “prevention of recurrent HE episodes” group, fewer HE events (0.79 vs 1.78; P = 0.013) were reported during the period of time when rifaximin was used. In the “prevention of recurrent acute exacerbations on persistent HE” group, there was no significant difference in the number of HE-events (1.48 vs 1.77; P = 0.582).CONCLUSIONIn this real-life experience, the effectiveness of rifaximin was confirmed in the prevention of HE episodes recurrence but was not proved in the prevention of acute exacerbations recurrence on persistent HE.

Alpha Stent for Coiling of Unruptured, Wide-Necked, Distal Internal Carotid Artery Aneurysms: Safety and Effectiveness at 6 Months.

ObjectiveThe Alpha stent (CGBio), a new intracranial stent featuring a re-sheathable mesh design with improved wall apposition at the curved segment, was clinically evaluated. We report the 6-month follow-up results from a prospective, single-center study in which the stent was used for coiling of wide-necked distal internal carotid artery (ICA) aneurysms.Materials and MethodsBetween April 2016 and 2018, 50 patients (mean age, 56.5 years, 45 females [90%]) with 54 unruptured distal ICA aneurysms (average diameter: 5.6 ± 1.7 mm) were enrolled. The primary endpoint for effectiveness was successful coil embolization with the Alpha stent, and subsequent complete or near-complete occlusion at the 6-month magnetic resonance angiography assessment. The primary safety endpoint was the absence of serious adverse events (SAEs) up to 6 months from the procedure.ResultsThe primary effectiveness endpoint was observed in 94.4% (51/54) aneurysms. In one patient with technical failure, the stent could not be deployed because of parent artery tortuosity; therefore, a different type of stent was used. Of the 53 aneurysms treated with the Alpha stent, complete occlusion was achieved in 64.1% (34/53) cases, and near-complete occlusion was achieved in 32.0% (17/53) cases by the 6-month follow-up. Two cases (3.7%) required retreatment because of major recurrence. In 4% (2/50) patients, SAEs, i.e., retinal artery thromboembolism and corona radiata lacunar infarction, were reported after the procedure.ConclusionFor endovascular treatment of unruptured, wide-necked, distal ICA aneurysms, coil embolization using the newly developed Alpha stent showed excellent procedural and mid-term clinical follow-up results in terms of effectiveness and safety.

Multicentre, non-interventional study of the efficacy and tolerability of linaclotide in the treatment of irritable bowel syndrome with constipation in primary, secondary and tertiary centres: the Alpine study

ObjectivesWe evaluated the effectiveness and tolerability of linaclotide, a minimally absorbed guanylate cyclase-C agonist, in patients with irritable bowel syndrome with constipation (IBS-C) in routine clinical practice.SettingA multicentre, non-interventional study...

The industrialization of ablation: a highly standardized and reproducible workflow for radiofrequency ablation of atrial fibrillation

Background or PurposeThe purpose of this analysis was to report on efficacy of a standardized workflow for atrial fibrillation (AF) ablation using technology advances such as 3D imaging and contact force sensing in a real-world setting.MethodsConsecutive AF ablations from 2014 to 2015 at a high-volume site in Belgium were included. The workflow consisted of a pre-specified procedure sequence including 3D modeling followed by radiofrequency encircling of the pulmonary veins (25 W posterior wall, 35 W anterior wall) with a THERMOCOOL SMARTTOUCH® Catheter guided by CARTO VISITAG™ Module (2.5 mm/5 s stability, 50% > 7 g) and ablation index (targets: 550 anterior wall, 400 posterior wall). Efficiency endpoints were procedure time, fluoroscopy time, and radiation dose. The primary effectiveness endpoint was freedom from atrial arrhythmia recurrence.ResultsA total of 605 paroxysmal AF (PAF) and 182 persistent AF (PsAF) patients were followed for 436 ± 199 days. Mean procedure times were short (PAF: 96.1 ± 26.2 min; PsAF: 109.2 ± 35.6 min) with most procedures (90.6% PAF; 81.3% PsAF) completed in ≤ 120 min. Minimal fluoroscopy was utilized (PAF: 6.1 ± 3.8 min, 5.9 ± 3.4 Gy*cm2; PsAF: 6.9 ± 4.7 min, 7.4 ± 4.9 Gy*cm2). Freedom from atrial arrhythmia recurrence was higher for PAF than PsAF patients (OR: 2.0, 95% CI: 1.4–2.9, p = 0.0003), but adjusted mean rates were high in both groups (81.0% vs. 67.9%). Rates were adjusted for prior ablation and age (at 65 years).ConclusionAF ablation using a standardized workflow resulted in low procedure times and variability, with minimal fluoroscopy exposure. Long-term freedom from atrial arrhythmia recurrence was high in both PAF and PsAF populations.

Safe, Effective Chin and Jaw Restoration With VYC-25L Hyaluronic Acid Injectable Gel.

VYC-25L, a hyaluronic acid soft-tissue filler with lidocaine, is designed to restore and create facial volume in the chin and jaw. To evaluate the safety and effectiveness of VYC-25L in subjects with chin retrusion. Adults with chin retrusion (145°-165° glabella-subnasale-pogonion facial angle) were randomized (3:1) to receive VYC-25L in the chin/jaw at study onset (treatment group) or 3 months later (control group). Primary effectiveness end point was mean change in facial angle from baseline at Month 3. Safety assessments included injection site responses (ISRs), recorded in a subject diary, and adverse events (AEs). VYC-25L was administered to 119 subjects (treatment group: n = 90; control group: n = 29). Mean change in facial angle from baseline at Month 3 was significantly greater in the treatment versus control group (difference: 2.51°; p < .0001). Effectiveness was also demonstrated by the proportion of subjects with improved/much improved Global Aesthetic Improvement Scale scores and responses on FACE-Q Satisfaction and Psychological Well-Being Scales. Treatment benefit remained evident at Month 12. Common ISRs were firmness (95.8%), tenderness (95.8%), and swelling (91.6%). No serious treatment-related AEs were reported. VYC-25L significantly improved glabella-subnasale-pogonion facial angle and was generally safe and well tolerated.

P4778Effectiveness and safety of rivaroxaban versus warfarin in nonvalvular atrial fibrillation patients with coronary or peripheral artery disease

Abstract Background The efficacy and safety of rivaroxaban use for the prevention of major thrombotic vascular events (MTVEs) has been demonstrated in randomized trials of nonvalvular atrial fibrillation (NVAF), coronary artery disease (CAD) and peripheral artery disease (PAD) patients. Purpose To assess the effectiveness and safety of rivaroxaban versus warfarin in preventing MTVEs in NVAF patients with concomitant CAD and/or PAD in routine practice. Methods Using MarketScan data from 1/2012–12/2017, we identified oral anticoagulant (OAC)-naïve NVAF patients with comorbid CAD and/or PAD and ≥12-months of insurance coverage before OAC initiation. Differences in baseline covariates between cohorts were adjusted using inverse probability-of-treatment weights based on propensity-scores (standardized differences &lt;0.1 achieved for all covariates after adjustment). The primary effectiveness endpoint was the composite of any MTVE including ischemic stroke, myocardial infarction or adverse limb event (revascularization or amputation). The primary safety endpoint was major bleeding defined using the Cunningham algorithm. Patients were followed until a MTVE, discontinuation or switch of index OAC, insurance disenrollment or end-of-data availability. Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing the cohorts were calculated using Cox regression. Results We identified 3,257 rivaroxaban (30.4% received a reduced dose) and 5,046 warfarin users with NVAF and comorbid CAD and/or PAD. Median (25%-75% range) age was 74 (65–81) years, CHA2DS2-VASc score was 3 (2–4). Rivaroxaban was associated with a 32% (95% CI=8–50%) reduction in the composite of any MTVE (Figure). No significant difference in major bleeding was observed (HR=1.13, 95% CI=0.84–1.52). Figure 1. Event Rates and Hazard Ratios Conclusions In patients with NVAF and comorbid CAD and/or PAD treated in routine practice, rivaroxaban use appears to reduce patients' risk of MTVEs compared to warfarin, without increasing their risk of major bleeding. This study lends further support to RCT findings that suggest rivaroxaban is effective in preventing major events in multiple vascular beds. Acknowledgement/Funding Bayer AG, Berlin, Germany

Rationale and design for a randomized, single-center, double-blind, sham-controlled study of non-invasive vagus nerve stimulation for treatment of post-traumatic headache

ObjectiveEvaluate the efficacy and safety of non-invasive vagus nerve stimulation (nVNS) for the treatment of post-traumatic headache (PTH).BackgroundWorldwide, ∼69 million people per year sustain a traumatic brain injury (TBI), many of whom develop PTH. Clinicians often treat PTH with drugs approved for primary headache disorders, and many patients self-treat with over-the-counter agents but have inadequate pain relief. There has been little study of therapies for PTH, and safe, effective treatments are needed.Design/MethodsThis randomized, double-blind, sham-controlled, parallel-group pilot study is enrolling adults who present 1–4 weeks after a head injury, meet International Classification of Headache Disorders 3rd edition (ICHD-3) criteria for acute headache attributed to mild TBI, and have ≥2 headaches/week with a migraine or probable migraine phenotype. After a 2-week run-in period, subjects are randomly assigned (1:1 allocation) to receive daily preventive therapy and as-needed acute treatment with nVNS or a sham device. Preventive therapy consists of two 120-second stimulations 3 times daily. Acute treatment comprises 2 stimulations at headache onset and 2 stimulations 20 minutes after the start of initial treatment. Subjects are not to use acute rescue medication for 120 minutes post-treatment. One North American site will enroll ≤80 subjects. The expected duration is 12 months (enrollment, 9 months; participation, 14 weeks).ResultsThe primary effectiveness end point is decrease in pain (on a 7-point scale) 60 minutes post-treatment for all treated headache attacks. Secondary end points include decrease in the frequency of headache days between the run-in period and the last 2 weeks of the double-blind period and responder rates (ie, percentages of subjects with ≥50% decrease in attack frequency). The primary safety end point is the incidence of treatment-related serious adverse events.ConclusionsThis study will assess the efficacy and safety of nVNS as a novel therapy for PTH.

STABLE II clinical trial on endovascular treatment of acute, complicated type B aortic dissection with a composite device design

ObjectiveTo evaluate the safety and effectiveness of a composite device design (covered stent graft and bare metal stent) for the treatment of patients with acute, complicated type B aortic dissection (TBAD) presenting with aortic rupture and/or branch vessel malperfusion. MethodsIn this prospective, nonrandomized, multicenter study, 73 patients (65.8% male; mean age, 60.7 years) with acute, complicated TBAD were enrolled between August 2012 and January 2015 to receive treatment with the Zenith Dissection Endovascular System (William Cook Europe, Aps, Bjaeverskov, Denmark) at institutions in the United States and Japan. The primary safety end point was the rate of freedom from major adverse events at 30 days, and the primary effectiveness end point was the rate of survival at 30 days. This article reports primary outcomes at 30 days and follow-up results through 1 year, reflecting study data as of March 2018. ResultsOf 73 patients, 20 presented with aortic rupture (27%) and 57 presented with branch vessel obstruction/compromise (78%), including 4 patients presenting with both conditions. The covered stent graft was used in all patients (median, 1; range, 1-3; 1 stent graft used in 64.4%; 47/73), and the bare metal dissection stent was used in 58 of 73 patients (79.5%). Thirty-day mortality occurred in five patients (6.8%): one procedure related, three unrelated to dissection repair, and one indeterminate. Thirty-day major adverse events included myocardial infarction (1.4%), bowel ischemia (1.4%), renal insufficiency/renal failure requiring dialysis (6.8%), stroke (6.8%), paraplegia or paraparesis (5.5%), and prolonged ventilatory support (13.7%). Nine deaths occurred from 31 to 365 days (only one death related to dissection repair); the Kaplan-Meier estimate of freedom from all-cause mortality was 80.3% ± 4.7% at 1 year. Within 365 days, 9 of 73 patients (12.3%) underwent 10 secondary interventions; no patients required conversion to open surgery. At the 12-month follow-up, complete or partial thrombosis of the false lumen was seen in 100% of patients (46/46) within the stent graft region and in 97.4% of patients (38/39) within the dissection stent region. Growth (>5 mm) of the maximum transaortic diameter was observed in 14.9% of patients (7/47) in the stent graft region and in 38.5% of patients (15/39) within the dissection stent region at 12 months. ConclusionsThirty-day and 1-year results from the STABLE II study demonstrated favorable clinical and anatomical outcomes for the treatment of rupture and malperfusion in the setting of acute, complicated TBAD. Five-year follow-up is ongoing.

Prospective study on embolization of intracranial aneurysms with the pipeline device: the PREMIER study 1 year results

BackgroundPreliminary clinical studies on the safety and efficacy of the pipeline embolization device (PED) for the treatment of small/medium aneurysms have demonstrated high occlusion rates with low complications.ObjectiveTo evaluate the...

Derivo Embolization Device for the Treatment of Intracranial Aneurysms.

Background and Purpose- Flow diverter technology improvements are necessary to provide safe and good results and enable the treatment of a larger variety of aneurysms. We report a nationwide experience with the Derivo Embolization Device in the treatment of intracranial aneurysms. Methods- BRAIDED (Brazilian Registry of Aneurysms Assigned to Intervention With the Derivo Embolization Device) is a multicenter, prospective, interventional, single-arm trial of the Derivo Embolization Device for the treatment of intracranial aneurysms. The primary effectiveness end point was total aneurysm occlusion at 6- and 12-month angiographies. The secondary safety end point was the absence of serious adverse events during follow-up. Univariable and multivariable logistic regression was performed to identify predictors of aneurysm persistence, periprocedural complications, and adverse events during follow-up. Results- Between December 2016 and October 2018, 146 patients harboring 183 intracranial aneurysms were treated in 151 interventions at 7 centers. Derivo Embolization Device placement was technically successful in all patients. Most aneurysms (86.9%) were located at the internal carotid artery, and the mean diameter was 6.7 mm. At 6 months, 113 of 140 (80.7%) aneurysms met the study's primary end point, and 74 of 83 (89.2%) met the study's primary end point at 12 months. Saccular morphology of the aneurysm (odds ratio, 5.66; 95% CI, 1.01-31.77) and the presence of a branch arising from the sac (odds ratio, 6.36; 95% CI, 2.11-22.36) predicted persistence. A long duration of follow-up (odds ratio, 0.86; 95% CI, 0.78-0.95) predicted total occlusion. Of the 146 enrolled patients, 138 (94.5%) were treated without serious adverse events during follow-up. In the multivariable analysis, aneurysms located at a sidewall were less likely to experience these events than those located at bifurcations (odds ratio, 0.07; 95% CI, 0.01-0.51). Conclusions- The Derivo Embolization Device is a safe and effective treatment for intracranial aneurysms. Clinical Trial Registration- URL: http://plataformabrasil.saude.gov.br/login.jsf. Unique identifier: CAAE 77089717.7.1001.5125.

Hybrid thoracoscopic surgical and transvenous catheter ablation versus transvenous catheter ablation in persistent and longstanding persistent atrial fibrillation (HARTCAP-AF): study protocol for a randomized trial

BackgroundSuccess rates with conventional transvenous endocardial pulmonary vein isolation in patients with persistent and longstanding persistent atrial fibrillation (AF) are variable due to advanced electrical and structural remodeling of the atria. As a consequence, more extensive endocardial lesions, minimally invasive thoracoscopic surgical techniques, and hybrid ablation (combining thoracoscopic epicardial surgical and endocardial catheter ablation) have been developed.HypothesisThe HARTCAP-AF trial hypothesizes that hybrid AF ablation is more effective than (repeated) transvenous endocardial catheter ablation in (longstanding) persistent AF, without increasing the number of associated major adverse events.MethodsThis randomized controlled trial will include 40 patients with persistent or longstanding persistent AF who will be 1:1 randomized to either hybrid ablation or (repeated) catheter ablation. The procedures and follow-up are conducted according to the guidelines. The primary effectiveness endpoint is freedom from any supraventricular arrhythmia lasting longer than 5 min without the use of Vaughan-Williams class I or III antiarrhythmic drugs through 12 months of follow-up after the last procedure. In the catheter ablation arm, a second procedure planned within 6 months after the index procedure is allowed for obtaining the primary endpoint. Additionally, adverse events, cost-effectiveness, and quality of life data will be recorded.Trial registrationClinicalTrials.gov, NCT02441738. Registered on 12 May 2015.

Sodium tanshinone IIA sulfonate prevents the adverse left ventricular remodelling: Focus on polymorphonuclear neutrophil-derived granule components.

AimsThe aims of this study were to evaluate the effects of sodium tanshinone IIA sulfonate (STS) on left ventricular (LV) remodelling after for ST‐elevated myocardial infarction (STEMI).Methods and resultsIn this prospective, randomized clinical trial, 101 patients with the ST‐elevated MI (STEMI) and a successful reperfusion were immediately randomized to receive STS (80 mg qd for 7 days) or saline control, along with standard therapy. The primary effectiveness endpoint is the % change in LV end diastolic volumes index (%∆ LVEDVi) as measured by echocardiography from baseline to 6 months. Secondary effectiveness endpoints include 6‐month period for major adverse cardiac events (MACE), including the occurrence of recurrent myocardial infarction, death, hospitalization for heart failure and malignant arrhythmia. The 6‐month changes in %∆ LVEDVi were significantly smaller in the STS group than in the control group [−5.05% vs 3.32%; P < 0.001]. With respect to MACE, there was a significant difference between those who received STS (8.16%) and those patients on control (26.00%) (P = 0.019). Meaningfully, results of parallel tests aimed at mechanistic explanation of the reported clinical effects, revealed a significantly reduced levels of neutrophils‐derived granule components in the blood of STS treated patients.ConclusionWe found that short‐term treatment with STS reduced progressive left ventricular remodelling and subsequent better clinical outcome that could be mechanistically linked to the inhibition of the ultimate damage of infarcted myocardium by infiltrating neutrophils.

A Prospective, Single-Arm, Multicenter Trial of Catheter-Directed Mechanical Thrombectomy for Intermediate-Risk Acute Pulmonary Embolism: The FLARE Study

ObjectivesThe aim of this study was to evaluate the safety and effectiveness of percutaneous mechanical thrombectomy using the FlowTriever System (Inari Medical, Irvine, California) in a prospective trial of patients with acute intermediate-risk pulmonary embolism (PE). BackgroundCatheter-directed thrombolysis has been shown to improve right ventricular (RV) function in patients with PE. However, catheter-directed thrombolysis increases bleeding risk and many patients with PE have relative and absolute contraindications to thrombolysis. MethodsPatients with symptomatic, computed tomography–documented PE and RV/left ventricular (LV) ratios ≥0.9 were eligible for enrollment. The primary effectiveness endpoint was core laboratory–assessed change in RV/LV ratio. The primary safety endpoint comprised device-related death, major bleeding, treatment-related clinical deterioration, pulmonary vascular injury, or cardiac injury within 48 h of thrombectomy. ResultsFrom April 2016 to October 2017, 106 patients were treated with the FlowTriever System at 18 U.S. sites. Two patients (1.9%) received adjunctive thrombolytics and were analyzed separately. Mean procedural time was 94 min; mean intensive care unit stay was 1.5 days. Forty-three patients (41.3%) did not require any intensive care unit stay. At 48 h post-procedure, average RV/LV ratio reduction was 0.38 (25.1%; p < 0.0001). Four patients (3.8%) experienced 6 major adverse events, with 1 patient (1.0%) experiencing major bleeding. One patient (1.0%) died, of undiagnosed breast cancer, through 30-day follow-up. ConclusionsPercutaneous mechanical thrombectomy with the FlowTriever System appears safe and effective in patients with acute intermediate-risk PE, with significant improvement in RV/LV ratio and minimal major bleeding. Potential advantages include immediate thrombus removal, absence of thrombolytic complications, and reduced need for post-procedural critical care.

A retrospective study of acupuncture as an adjunctive therapy to topical ibuprofen for chronic knee pain due to osteoarthritis.

This retrospective study investigated the effectiveness and safety of acupuncture as an adjunctive therapy to topical ibuprofen (TIP) for patients with chronic knee pain (CKP) due to osteoarthritis.This retrospective study analyzed medical records of 84 patients with CKP due to osteoarthritis. These patients were divided into a treatment group (n = 42) and a control group (n = 42). The patients in the treatment group were treated with acupuncture plus TIP, while the subjects in the control group received TIP monotherapy. The primary effectiveness endpoint was assessed by Western Ontario and McMaster Universities osteoarthritis index (WOMAC). The secondary effectiveness endpoints were evaluated by the numeric rating scale (NRS), 12-item Short FormHealth Survey (SF-12, mainly including mental component summary [MCS], and physical component summary [PCS]), and adverse events. All patients received an 8-week treatment. All endpoints were measured pre-treatment and posttreatment.The patients who received acupuncture plus TIP showed better effectiveness in both primary endpoint of WOMAC scale (pain, P < .01; function, P < .01; and stiffness, P < .01) and secondary endpoints of NRS (P < .01), and SF-12 (MCS, P < .01; and PCS, P < .01), than patients who received TIP monotherapy. In addition, both groups had similar safety profile.The results of this study showed that the effectiveness of acupuncture plus TIP may be better than TIP monotherapy for patients with CKP due to osteoarthritis.

Real-world effectiveness and safety of glecaprevir/pibrentasvir for the treatment of chronic hepatitis C infection: data from the German Hepatitis C-Registry.

Glecaprevir/pibrentasvir is a pangenotypic direct-acting antiviral regimen approved for treating adults chronically infected with hepatitis C virus (HCV). There are limited real-world data on glecaprevir/pibrentasvir to date. To evaluate the effectiveness and safety of glecaprevir/pibrentasvir under real-world conditions in the German Hepatitis C-Registry (DHC-R). The DHC-R is an ongoing, non-interventional, multicentre, prospective, observational cohort study that monitors patients with chronic HCV infection. Data were collected from patients who initiated glecaprevir/pibrentasvir and completed a screening visit on or after 2 August 2017. The primary effectiveness endpoint was sustained virological response at post-treatment Week 12 (SVR12). Safety and tolerability were also assessed. As of 15 July 2018, 586 patients received glecaprevir/pibrentasvir and had documented SVR12 data, treatment discontinuation, loss to follow-up or HCV reinfection. Five hundred and fifty-two patients (94%) received on-label treatment. At baseline, most on-label patients were infected with HCV genotype 1 (53%) or 3 (33%), HCV treatment-naïve (90%), without cirrhosis (94%), and treated for 8weeks (93%). Five hundred and thirty-four patients (96.7%) achieved SVR12 (intention-to-treat [ITT] analysis). By modified ITT analysis (excluding patients who discontinued and did not achieve SVR12 or patients lost to follow-up), the SVR12 rate was 99.4% (n/N=534/537). There was one documented virological failure (relapse) and two documented HCV reinfections. One hundred and forty-two (26%) adverse events (AEs) and 9 (2%) serious AEs occurred; 2 (<1%) AEs led to treatment discontinuation. All patients treated off-label (N=34) achieved SVR12. Glecaprevir/pibrentasvir was highly effective and well tolerated under real-world conditions. Clinical trial number: DRKS00009717 (German Clinical Trials Register, DRKS).

Drug-Coated Balloon Treatment for Femoropopliteal Artery Disease: The Chronic Total Occlusion Cohort in the IN.PACT Global Study

ObjectivesThis study evaluated the 12-month safety and effectiveness of a paclitaxel drug-coated balloon for treatment of intermittent claudication or rest pain in subjects with femoropopliteal chronic total occlusions (CTO). BackgroundCTOs are difficult to treat, and the optimal intervention remains to be determined. MethodsThe IN.PACT Global Study is an international single-arm study that enrolled 1,535 patients with symptomatic femoropopliteal artery disease. The study contains prospectively defined cohorts with prospectively planned imaging analyses, including a CTO (≥5 cm) cohort in which subjects underwent duplex ultrasonography analyzed by an independent core laboratory. The primary safety endpoint was a composite of freedom from device- and procedure-related mortality through 30 days, and freedom from major target limb amputation and target vessel revascularization through 12 months. An independent Clinical Events Committee adjudicated all adverse events. The primary effectiveness endpoint was primary patency at 12 months, defined as freedom from clinically driven target lesion revascularization and freedom from restenosis. ResultsThe CTO imaging cohort had 126 subjects with 127 lesions (mean lesion length 22.83 ± 9.76 cm). Primary patency by Kaplan-Meier estimate was 85.3% through 12 months. Provisional stenting was performed in 46.8% of lesions. The primary safety composite endpoint was achieved by 88.7% of subjects. There were no device- or procedure-related deaths through 30 days or major target limb amputations through 12 months. ConclusionsThe paclitaxel drug-coated balloon was safe and highly effective at 12 months after treatment of subjects with CTO ≥5 cm in the femoropopliteal arteries. (IN.PACT Global Clinical Study; NCT01609296)

Overview of the 2018 US Food and Drug Administration Circulatory System Devices Panel meeting on the INCRAFT AAA Stent Graft System.

On June 12, 2018, the US Food and Drug Administration (FDA) convened a meeting of the Circulatory System Devices Panel to advise on the safety and effectiveness of the INCRAFT® AAA Stent Graft System for the treatment of abdominal aortic aneurysms (AAA) and to consider a premarket approval application sponsored by Cordis, Inc., for Unique identifier: NCT01664078 based on the results of the pivotal INSPIRATION trial (URL: https://clinicaltrials.gov/ct2/show/NCT01664078). The INCRAFT® AAA Stent Graft System is designed for endovascular repair of infrarenal AAAs with complex aortic anatomies. The stent-graft system utilizes nitinol stent and polyester graft technology in an ultra-low profile delivery system, with the goal of isolating the aneurysmal sac and preventing sac rupture. The multicenter, prospective, non-randomized investigation trial met its primary composite safety and effectiveness endpoints but also showed higher-than-anticipated rates of stent fracture and endoleaks. The committee discussion focused on how these events impact the long-term safety and effectiveness, as well as the benefit/risk profile, of the device. While the panel acknowledged the risk of the device, the panel's final vote supported that the benefits of the INCRAFT AAA Stent Graft System outweigh the risks and that a post-marketing study should be mandated. The FDA approved the device for use in complex access anatomies in December 2018.

Abstract WMP35: A Novel Microporous Covered Stent NCVC-CS1 for the Treatment of Intracranial Aneurysms: Its Functional Features and Preliminary Results of Clinical Trial

Background and Purpose: The treatment for large and giant intracranial aneurysms remains unsatisfactory even after the introduction of flow diverters, especially in those located in posterior circulation. This study was aimed to assess the novel covered stent graft named NCVC-CS1 for the treatment of such complex aneurysms. Materials and Methods: NCVC-CS1 is a balloon-expandable stent covered with a thin, microporous segmented polyurethane membrane. After the confirmation of its function on navigability, aneurysm occlusion, and patency of branching vessels using animal models, an investor-initiated, first-in human clinical trial to evaluate the safety and efficacy of NCVC-CS1 was conducted. The inclusion criteria for the targeted aneurysm were unruptured, wide-necked aneurysms more than 7 mm, located in petrous/cavernous portion of ICA, intradural VA, or BA proximal to the orifice of superior cerebellar artery. The primary effectiveness endpoint was angiographic evaluation that demonstrated complete aneurysm occlusion and patency of target vessel (less than 50% stenosis) at 180 days. The primary safety endpoint was occurrence of any stroke or death related to the procedure. Results: A total of 10 patients were enrolled in the trial. Among them, nine aneurysms were large (more than 10mm) including one giant aneurysm (more than 25mm). Mean aneurysm size was 14.3mm. Five aneurysms (50%) were located in VA. NCVC-CS1 placement was technically successful in all cases. No coils were used. The instant cessation of inflow to the targeted aneurysm at the time of the procedure (so-called eclipse sign) was observed in nine cases (90%). Among the nine cases whose follow-up data at 180 days were obtained, five (55%) met the study’s primary effectiveness endpoint whereas the other four showed near complete occlusion without stenosis of the parent artery. As to the safety endpoint, one patient experienced a non-disabling infarction. No subsequent rupture of the aneurysm was observed during the follow-up period. Conclusion: NCVC-CS1 showed the safety and efficacy on its first-in-human clinical trial. This device can offer another therapeutic choice for wide-necked and large intracranial aneurysms.

Abstract WMP36: Surpass™ IntraCranial Aneurysm EmbolizatioN System Pivotal Trial to Treat Large OR Giant Wide Neck Aneurysms (SCENT Trial): One Year Outcomes

Introduction: Surpass™ Flow Diverter was developed to treat large or giant wide-neck intracranial aneurysms (IA) not amenable to surgical or current standard endovascular treatment due to location, morphology, or known treatment challenges. FDA approved on July 13 2018, Surpass™ fulfills an unmet clinical need. Indications for Use allow for placement in the entire intracranial internal carotid artery (ICA). Surpass™ is available in diameters of 3 to 5 mm and lengths of 15 to 50 mm. Methods: SCENT Trial is an international, multi-center, prospective, non-randomized trial comparing the outcomes of Surpass™ Flow Diverter treatment to historical control. It is designed to evaluate the safety and efficacy of Surpass™ for treatment of wide-neck (≥4mm), large or giant IA ≥10 mm in size. The primary safety endpoint is the percent of subjects experiencing neurologic death or major ipsilateral stroke at 12 months. The primary effectiveness endpoint is the percent of subjects with 100% occlusion (Raymond Class 1) without clinically significant stenosis (≤50% stenosis) of the parent artery, and any retreatment of the target aneurysm at 12-month. Results: From 2012 to 2015, 180 subjects were treated at 26 sites. Mean age was 61.0 years and 91.7% (165/180) were females. Aneurysms were most frequently located in the carotid-ophthalmic segment (33.3%; 60/180), followed by the cavernous segment (28.9%; 52/180), posterior communicating artery (21.1%; 38/180), supraclinoid carotid artery (11.1%; 20/180), superior hypophyseal artery (3.3%; 6/180), and the petrous segment (2.2%; 4/180). Mean aneurysm dimension included dome height 13.4±5.7 mm. Mean neck width was 6.7 mm. Technical success occurred in 97.8% (176/180) of subjects while the mean number of Surpass™ devices used was 1.1 per procedure, with 86.7% (156/180) of aneurysms treated with a single flow diverter. The 12-month primary effectiveness rate was 62.8% [(113/180), 95% CI 55.3, 69.9] and 12-month major ipsilateral stroke or neurological death rate of 10.6% [(19/180), 95% CI 55.3, 69.9] Conclusions: Surpass™ Flow Diverter is safe and effective to treat large and giant aneurysms intracranial internal carotid aneurysms.