Woodward, Keith

BACKGROUND: The EXCELLENT registry aimed to evaluate the effectiveness of the EMBOTRAP Revascularization Device in an all-comer population in a real-world setting, with a focus on the composition of retrieved clots. METHODS: EXCELLENT is a prospective, global registry of patients with acute ischemic stroke treated with EMBOTRAP as the first-line mechanical thrombectomy device conducted at 34 sites (25 sites contributing clot) from September 2018 to March 2021, utilizing core imaging and central histology laboratories blinded to clinical data, independent 90-day modified Rankin Scale assessment and Clinical Events Committee. RESULTS: After screening 3799 patients, a total of 997 subjects (mean age, 70.0±14.2 years; 51.8% women; 19.7% non-White) were included. The first-pass modified Treatment in Cerebral Infarction (mTICI) ≥2b rate was 64.5% (623/966), first-pass mTICI ≥2c was 39.1% (378/966), and final mTICI ≥2b was 94.5% (931/985). A total of 427/912 (46.8%) patients achieved a 90-day modified Rankin Scale of 0 to 2 or ≤baseline. Embolization to a new territory occurred in 0.2% (2/984), and symptomatic intracranial hemorrhage at 24 hours in 1.6% (16/997). The 90-day mortality was 19.1% (175/918). Device- and/or procedure-related serious adverse events occurred in 5.9% (54/912) through 90 days. The mean RBC percentage of retrieved clots was 45.62±21.372. Among patients who achieved mTICI ≥2b with the first pass, 15.7% (52/331) and 9.7% (32/331), respectively, had RBC-poor (<25%) and RBC-rich (>75%) clots. Patients with no clot retrieved in any procedural pass had a lower percentage of hyperdense or susceptibility vessel sign on baseline imaging (58.9% versus 74.7%; P <0.001), pointing to a potential preprocedure indicator of challenging clot. CONCLUSIONS: The EXCELLENT registry informs real-world practices in mechanical thrombectomy and sheds light on the range of clots effectively retrieved by current technology. This is the first report of detailed patient characteristics where mechanical thrombectomy maneuvers failed to remove any clot material. Although the composition of nonretrievable clots cannot be assessed histologically, the results support the notion that no retrieval may be correlated with imaging findings suggesting clots lower in RBC. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03685578.

Introduction EXCELLENT (NCT03685578; Cerenovus) is a large, prospective, international, real‐world registry of endovascular clot removal in acute ischemic stroke (AIS) with EmboTrap as the first line mechanical thrombectomy (MT) device, which included collection and analysis of the retrieved thrombus material. Methods Between September 2018 and March 2021, 1000 “all‐comer” patients were enrolled at 34 global sites (27 US, 5 EU, 1 UK, 1 Israel) and treated according to standard of care at each center (with Embrotrap as first line). The study employed blind endpoint evaluation, including a core imaging lab and an independent 90‐day mRS assessment. Retrieved clot was collected per each MT maneuver from 538 subjects across 26 sites and clot analysis was performed by independent central labs blinded to clinical data. Results mITT population included 998 subjects. Mean age was 69.9±14.18 years (range 18–102), 51.8% (517/998) subjects were female and 9.9% (97/997) had a pre‐stroke mRS 3–5. Baseline NIHSS was 15.6±6.87 (range 0–36); 10.1% (82/815) subjects had a large core (ASPECTS 0–5); 5.8% (57/990) had posterior stroke; 56.3% (523/929) underwent MT ≤ 6hrs of onset and 38.1% (380/998) received IV‐tPA prior to MT. First pass eTICI 2c‐3 was achieved in 38.3% (377/984) and final 2b‐3 in 94.5 % (930/984; median number of passes = 1) of subjects. 90‐day mRS≤2 or ≤pre‐stroke was 46.9% (429/915) and 90‐day all‐cause mortality was 19.0% (175/921). The univariate analysis of clot components showed high red blood cell and low platelet content were significant predictors of good mRS outcome (p < 0.001 and 0.009) and negative predictors of 90‐day mortality (p < 0.001 and 0.017, respectively). Conclusions This large multi‐center, all‐comer cohort reflects the population undergoing thrombectomy today in a real world‐setting. Final angiographic, clinical and thrombus composition results, along with multivariate analysis of predictors of clinical outcomes, will be presented at the time of the conference.

Despite the proven benefit of stent retrievers, challenges to rapid revascularization of large vessel occlusions (LVO) persist. Current stent retrievers have limited effectiveness for removing organized thrombi. The NeVa device is a novel stent retriever designed with openings in the basket cell structure (“drop zones”) intended to capture organized thrombi within the central scaffold during retrieval. Prospective, multicenter, open label, single arm, FDA-regulated IDE study to evaluate the performance of the NeVa device for recanalizing occluded intracranial vessels including ICA, M1/M2 MCA, and vertebrobasilar arteries, within 8 hours of onset. Primary endpoint was rate of eTICI 2b-3 within 3 NeVa passes, tested for non-inferiority against a performance goal of 72% with a margin of -10%. Additional efficacy endpoints included first pass effect to eTICI 2b-3 (FPE) and 90-day mRS 0-2. Primary safety endpoint was 90-day mortality. (ClinicalTrials.gov NCT04514562) (Site-adjudicated revascularization results are reported here. Final core lab results will be presented at the conference.) From April 1, 2021 to April 28, 2022, 139 subjects were enrolled at 25 centers in the US and Europe. Mean age was 67 ± 13 years; 47% were female. Median NIHSS score was 16 (IQR: 12-20). Occlusions were 14 (10%) ICA, 85 (61%) M1, 38 (27%) M2, 1 (1%) Basilar and 1 (1%) PCA. Mean time to first pass was 19 ± 12 minutes. eTICI 2b-3 within 3 NeVa passes occurred in 87.8% (122/139; CI 81.1%,92.7%; non-inferiority p<0.0001; post hoc superiority p=0.002, tested against performance goal of 72%). FPE (to eTICI 2b-3) was observed in 67.6% (94/139), with first pass to eTICI 2b67-3 in 61.2% (85/139) and to eTICI 2c-3 in 43.9% (61/139). Median number of passes was 1 (IQR 1-2). Final eTICI 2b-3 rate was 94.2% (131/139); final eTICI 2c-3 rate was 65.5% (91/139). Good outcome (90-day mRS 0-2) was seen in 62.6% (87/139) and was 74.4% in patients with FPE (70/94 vs. 17/45 (37.8%) without FPE; p<0.0001). Mortality was 9.4% (13/139) with sICH in 8 (5.8%) subjects. The NeVa device is effective and safe for revascularization of LVO strokes and demonstrates high first pass success in this international multicenter study. First pass reperfusion (eTICI 2b-3) was strongly associated with functional independence.

Introduction: EXCELLENT (NCT03685578) is a global prospective, multicenter, real-world registry of mechanical thrombectomy for stroke with the EmboTrap device as first line treatment which includes clot collection and analysis. Aim of the study: To report the rates of clinical outcomes and clot characteristics associated with first pass reperfusion in EXCELLENT. Methods: Per pass angiographic outcomes assessed by an independent core lab were available in 984 subjects Analysis of clot from 538 cases was performed by independent central labs blinded to clinical data. 90-day mRS assessment was blinded to subject data. Results: First pass reperfusion of mTICI 2b-3 (63.2%) and 2c-3 (38.3%) was significantly predictive of mRS 0-2 or ≤pre-stroke (p=0.011 and p=0.016) but not all-cause mortality at 90 days (p=0.080 and p=0.123, respectively). Further, mTICI 2c-3 in one pass was associated with a higher rate of mRS 0-2 or ≤pre-stroke vs. mTICI 2c-3 reperfusion in >1 pass, (55.5% and 45.1%, respectively, p=0.013) and a rate of all-cause mortality at 90 days of 14.6% vs. 19.8% (p=0.097). Full patient characteristics and clinical outcomes are shown in Table 1. Notable clot composition findings included: RBC (%, mean±SD): mTICI 2c-3, 1 pass 47.69±22.25, mTICI 2c-3, >1 pass 43.86±19.05, (p=0.088); fibrin: mTICI 2c-3, 1 pass 23.20±13.80, mTICI 2c-3 >1 pass 25.40 ± 13.52 (p=0.131); von Willebrand factor (VWF): mTICI2c-3, 1 pass 16.09±14.62, mTICI 2c-3, >1 pass 19.42±17.15 (p=0.038). Conclusions: First pass reperfusion in the EXCELLENT registry was associated with better clinical outcomes at 90 days. Clots retrieved with first pass reperfusion had higher RBC and lower fibrin and VWF content compared to those who achieved reperfusion at greater than one pass.