Citations

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.

Background Relationships between occlusive clot histopathology, baseline characteristics, imaging findings, revascularization rates, and clinical outcomes of stroke patients with large vessel occlusion (LVO) are not well understood. This study will assess the real-world experience on the efficacy and safety of using the EmboTrap device as the first approach in LVO patients and explore the associations between clot histological characteristics, imaging and clinical findings, revascularization rates, and clinical outcomes. Methods Prospective, global, multicenter, single-arm, imaging core laboratory, and clot analysis central laboratory observational registry. Adult patients (>18 years) with LVO, treated with EmboTrap as the first attempted device, will be eligible for study participation. Results Up to 1000 subjects at 50 international sites may be enrolled. Occlusive clots will be collected from at least 500 subjects. Independent central and imaging core laboratories will perform clot analysis and image adjudication. Statistical analysis will assess the association between imaging and clinical findings, clot characteristics, subject comorbidities, revascularization, and clinical outcomes. Study endpoints are functional independence (modified Rankin Scale score ≤2 at 90 days), expanded Thrombolysis In Cerebral Infarction (eTICI) score ≥2b50 rate, first-pass effect, number of passes, embolization into new territory, symptomatic intracranial hemorrhage, and 90-day mortality. Conclusions The EXCELLENT registry will provide reproducible effectiveness and safety data of EmboTrap for its use for mechanical thrombectomy. Additionally, the study will characterize the blood clots retrieved during mechanical thrombectomy with respect to their composition and histopathological analysis and potential correlations with clinical and imaging findings. Trial registration number NCT03685578 .

Limited data exist on clot composition and detailed characteristics of arterial thrombi associated with large vessel occlusion in acute ischemic stroke. Advances in endovascular thrombectomy and related imaging modalities have created a unique opportunity to analyze thrombi removed from cerebral arteries. Insights into thrombus composition, etiology, physical properties and neurovascular interactions may lead to future advancements in acute ischemic stroke treatment and improved clinical outcomes. Advances in imaging techniques may enhance clot characterization and inform therapeutic decision-making prior to treatment and reveal stroke etiology to guide secondary prevention. Current imaging techniques can provide some information about thrombi, but there remains much to evaluate about relationships that may exist among thrombus composition, occlusion characteristics and treatment outcomes. Improved pathophysiological characterization of clot types, their properties and how these properties change over time, together with clinical correlates from ongoing studies, may facilitate revascularization with thrombolysis and thrombectomy. Interdisciplinary approaches covering clinical, engineering and scientific aspects of thrombus research will be key to advancing the understanding of thrombi and improving acute ischemic stroke therapy. This consensus statement integrates recent research on clots and thrombi retrieved from cerebral arteries and provides a rationale for further analyses, including current opportunities and limitations.