Abstract WP68: Tissue Type Plasminogen Activator (t-PA) and Edaravone Combination Therapy Study (YAMATO Study)

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Junya Aoki ◽  
Kazumi Kimura ◽  
Norifumi Metoki ◽  
Yohei Tateishi ◽  
Kenichi Todo ◽  
...  

Introduction&Hypothesis: The aim of the present study was to investigate whether administration of edaravone, a free radical scavenger, before or during t-PA administration can increase the rate of early recanalization and improve the clinical outcome in stroke patients with major arterial occlusion. Methods: YAMATO study is an investigator initiated, multicenter (17 hospitals in Japan), prospective, randomized, open labeled study. Acute stroke patients with horizontal (M1) or vertical (M2) portion of the middle cerebral artery occlusion within 4.5 h of onset were studied. The subjects were randomly allocated to the early edaravone (early-E) group (intravenous edaravone [30 mg] was started before or during t-PA administration) and the late edaravone (late-E) group (edaravone was started after t-PA administration). Primary outcome, defined as any early recanalization 1h after t-PA therapy. Secondary outcomes included the rate of the significant recanalization, defined as ≥50% of the territory of the occluded artery on magnetic resonance angiography, or the thrombolysis in cerebral infarction score ≥2b on digital subtraction angiography as well as the incidence of symptomatic intracerebral hemorrhage (sICH), and the favorable clinical outcome (modified Rankin scale [mRS] of 0-2) at 3 months after onset. Results: One-hundred and sixty-six patients (96 men; median age [interquartile range], 78 [69-85] years) were randomized 1:1 to either the early-E group or the late-E group. Twenty-three (13.9%) had proximal M1 occlusion; 60 (36.1%), distal M1 occlusion; 83 (50%), M2 occlusion. Early recanalization was similarly observed in the early-E group and in the late-E group (53.1% vs. 53.0%, P=1.000). The rate of significant recanalization was also similar between the 2 groups (27.2% vs. 33.7%, p=0.399). sICH was occurred in 4 (4.8%) patients in the early-E group and in 2 (2.4%) in the late-E group (p=0.682). Among the 144 patients who were pre-morbid mRS of 0-2 and eligible for 3 months assessment, favorable outcome was seen in 53.9% in the early-E group and 57.4% in the late-E group (p=0.738) Conclusions: The timing of the edaravone infusion should not affect the rate of early recanalization, sICH, or favorable outcome after t-PA therapy.

2018 ◽  
Vol 79 (5-6) ◽  
pp. 335-341
Author(s):  
Junya Aoki ◽  
Kentaro Suzuki ◽  
Satoshi Suda ◽  
Seiji Okubo ◽  
Masahiro Mishina ◽  
...  

Background: It is unknown whether the effect of onset-­­to-door (OTD) time on clinical outcomes differs between ­patients with and without large artery occlusion (LAO) who undergo hyperacute recanalization therapy. Methods: Hyperacute recanalization therapy includes intravenous thrombolysis tissue-plasminogen activator (tPA), and endovascular therapy (EVT). Favorable clinical outcome was defined as modified Rankin Scale of ≤2 at discharge. Results: Among 164 patients, 117 (71%) patients received tPA, 86 (52%) received EVT, and 39 (24%) received tPA and EVT. One hundred and fifteen patients (70%) were classified into the LAO group and 49 (30%) into the non-LAO group. In the total cohort, multivariate regression analysis showed OTD time (OR 0.809 [95% CI 0.693–0.944], p = 0.007) was an independent factor related to the favorable outcome. Similarly, among patients with LAO, OTD was an independent negative factor for the favorable outcome (0.779 [0.646–0.940], p = 0.009). On the contrary, OTD was not associated with the favorable outcome (1.5 [0.7–2.5] vs. 1.7 [1.1–3.2], p = 0.155) in patients without LAO. This was confirmed with multivariate regression analysis, which did not show OTD to be an independent factor for the favorable outcome (0.900 [0.656–1.236], p = 0.516). Conclusion: The effect of early hospital arrival on clinical outcome differed between patients with and without LAO.


Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Ruediger Von Kummer ◽  
Andrew M Demchuk ◽  
Lydia D Foster ◽  
Bernard Yan ◽  
Wouter J Schonewille ◽  
...  

Background: Data on arterial recanalization after IV t-PA treatment are rare. IMS-3 allows the study of variables affecting arterial recanalization after IV t-PA in acute ischemic stroke patients with CTA-proved major artery occlusions. Methods: Of 656 acute ischemic stroke patients in IMS-3, 306 were examined with baseline CTA and randomized either to IV t-PA (N=95) or to IV t-PA followed by digital subtraction angiography (DSA) and endovascular therapy (EVT) (N=211). Comparison of baseline CTA to DSA within 5 hours of stroke onset assessed early arterial recanalization after IV t-PA. A central core lab categorized DSA vessel occlusion as “no, partial, or complete”. We studied the association between arterial occlusion sites on baseline CTA with early recanalization for the endovascular group and analyzed its impact on clinical outcome at 90 days. Results: In the EVT group, 22 patients (10.4%) had no CTA intracranial occlusions, but 1 extracranial occlusion; 42 patients (19.9%) had occlusions of intracranial internal carotid artery (ic-ICA); 10 patients (4.7%) had tandem occlusions of the cervical ICA and middle cerebral artery (MCA); 95 patients (45.0%) had MCA-trunk (M1) occlusions, 33 patients (15.6%) had M2 occlusions, 3 patients (1.4%) had M3/4 occlusions, and 6 patients (2.8%) occlusions within posterior circulation. Partial or complete recanalization occurred in 28.6% of patients before DSA and was marginally associated with occlusion site (p=0.0525) (8 patients (19.0%) with ic-ICA occlusion, 0 patients with tandem ICA/MCA occlusions, 34 patients (35.8%) with M1 occlusions, 11 patients (33.3%) with M2 occlusions, 0 patients with M3/4 occlusions, and 1 patient (16.7%) with occlusion within posterior circulation). Three CTA negative patients had intracranial occlusions on DSA. Thirty-two patients (59.3%) with early recanalization achieved mRS of 0-2 at 90 days compared to 51 patients (38.4%) without early recanalization (p=0.0099). There was no relationship between early recanalization and time to IV t-PA or mean t-PA dose. Conclusion: Before EVT, IV rt-PA may facilitate arterial recanalization and better clinical outcome in about one third of patients.


2016 ◽  
Vol 5 (3-4) ◽  
pp. 118-122 ◽  
Author(s):  
Marie L. Schmitz ◽  
Sharon D. Yeatts ◽  
Thomas A. Tomsick ◽  
David S. Liebeskind ◽  
Achala Vagal ◽  
...  

Background: Prompt revascularization is the main goal of acute ischemic stroke treatment. We examined which revascularization scale - reperfusion (modified Treatment in Cerebral Infarctions, mTICI) or recanalization (Arterial Occlusive Lesion, AOL) - better predicted the clinical outcome in ischemic stroke participants treated with endovascular therapy (EVT). Additionally, we determined the optimal thresholds for the predictive accuracy of each scale. Methods: We included participants from the Interventional Management of Stroke (IMS) III trial with complete occlusion in the internal carotid artery terminus or proximal middle cerebral artery (M1 or M2) who completed EVT within 7 h of symptom onset. The abilities of the AOL and mTICI scales to predict a favorable outcome (defined as a modified Rankin Scale score of 0-2 at 3 months) were compared by receiver operating characteristic analyses. The maximal sensitivity and specificity for each revascularization scale were established. Results: Among 240 participants who met the study inclusion criteria, 79 (33%) achieved a favorable outcome. Higher scores of mTICI and AOL increased the likelihood of a favorable outcome (2.7% with mTICI 0 vs. 83.3% with mTICI 3, and 3.0% with AOL 0 vs. 43% with AOL 3). The accuracy of mTICI reperfusion and AOL recanalization for a favorable outcome prediction was similar, with optimal thresholds of mTICI 2b/3 and AOL 3, respectively. Conclusion: Reperfusion (mTICI) and recanalization (AOL) predicted a favorable clinical outcome with comparable accuracy in ischemic stroke participants treated with EVT. Optimal revascularization goals to maximize clinical outcome (modified Rankin Scale score of 0-2) consisted of complete recanalization (AOL 3) and reperfusion of at least 50% of the arterial tree of the symptomatic artery (mTICI 2b/3) in the IMS III trial setting.


Stroke ◽  
2018 ◽  
Vol 49 (Suppl_1) ◽  
Author(s):  
Takashi Johno ◽  
Hiroyuki Kawano ◽  
Masataka Torii ◽  
Hiroshi Kamiyama ◽  
Tatsuo Amano ◽  
...  

2012 ◽  
Vol 313 (1-2) ◽  
pp. 132-136 ◽  
Author(s):  
Kazumi Kimura ◽  
Juya Aoki ◽  
Yuki Sakamoto ◽  
Kazuto Kobayashi ◽  
Kenichi Sakai ◽  
...  

Stroke ◽  
2019 ◽  
Vol 50 (4) ◽  
pp. 880-888 ◽  
Author(s):  
Johannes Kaesmacher ◽  
Panagiotis Chaloulos-Iakovidis ◽  
Leonidas Panos ◽  
Pasquale Mordasini ◽  
Patrik Michel ◽  
...  

Background and Purpose— If anterior circulation large vessel occlusion acute ischemic stroke patients presenting with ASPECTS 0–5 (Alberta Stroke Program Early CT Score) should be treated with mechanical thrombectomy remains unclear. Purpose of this study was to report on the outcome of patients with ASPECTS 0–5 treated with mechanical thrombectomy and to provide data regarding the effect of successful reperfusion on clinical outcomes and safety measures in these patients. Methods— Multicenter, pooled analysis of 7 institutional prospective registries: Bernese-European Registry for Ischemic Stroke Patients Treated Outside Current Guidelines With Neurothrombectomy Devices Using the SOLITAIRE FR With the Intention for Thrombectomy (Clinical Trial Registration—URL: https://www.clinicaltrials.gov . Unique identifier: NCT03496064). Primary outcome was defined as modified Rankin Scale 0–3 at day 90 (favorable outcome). Secondary outcomes included rates of day 90 modified Rankin Scale 0–2 (functional independence), day 90 mortality and occurrence of symptomatic intracerebral hemorrhage. Multivariable logistic regression analyses were performed to assess the association of successful reperfusion with clinical outcomes. Outputs are displayed as adjusted Odds Ratios (aOR) and 95% CI. Results— Two hundred thirty-seven of 2046 patients included in this registry presented with anterior circulation large vessel occlusion and ASPECTS 0–5. In this subgroup, the overall rates of favorable outcome and mortality at day 90 were 40.1% and 40.9%. Achieving successful reperfusion was independently associated with favorable outcome (aOR, 5.534; 95% CI, 2.363–12.961), functional independence (aOR, 5.583; 95% CI, 1.964–15.873), reduced mortality (aOR, 0.180; 95% CI, 0.083–0.390), and lower rates of symptomatic intracerebral hemorrhage (aOR, 0.235; 95% CI, 0.062–0.887). The mortality-reducing effect remained in patients with ASPECTS 0–4 (aOR, 0.167; 95% CI, 0.056–0.499). Sensitivity analyses did not change the primary results. Conclusions— In patients presenting with ASPECTS 0–5, who were treated with mechanical thrombectomy, successful reperfusion was beneficial without increasing the risk of symptomatic intracerebral hemorrhage. Although the results do not allow for general treatment recommendations, formal testing of mechanical thrombectomy versus best medical treatment in these patients in a randomized controlled trial is warranted.


2015 ◽  
Vol 8 (11) ◽  
pp. 1119-1122 ◽  
Author(s):  
Paul-Emile Labeyrie ◽  
Hocine Redjem ◽  
Raphaël Blanc ◽  
Marc-Antoine Labeyrie ◽  
Bruno Bartolini ◽  
...  

Background and purposeThe angiography based Capillary Index Score (CIS) has recently emerged as a potential surrogate marker of cerebral perfusion before intra-arterial thrombolysis. We assessed the prevalence of a favorable CIS (f-CIS) and its relationship with clinical outcome in patients treated by mechanical thrombectomy (MT).MethodsData from consecutive patients treated by MT from acute middle cerebral artery (MCA) occlusion were retrospectively analyzed. CIS was calculated from a pre-intervention cerebral angiogram. Association with favorable clinical outcome (modified Rankin Scale score ≤2) at 3 months was assessed in multivariate analysis.Results146 patients were included in the study. f-CIS was observed in 106/146 (72%) patients with an acceptable inter-rater agreement (κ=0.73, p<0.001). It was associated with a lower pretreatment National Institutes of Health Stroke Scale (NIHSS) score (p=0.014), an isolated M1/M2 occlusion without internal carotid occlusion (p=0.042), and an Alberta Stroke Program Early CT Score (ASPECTS) >4 (p=0.004). In binary regression, a favorable outcome was independently associated with f-CIS (OR (−95% CI, +95% CI)=3.8 (1.3 to 10.9), p=0.013), as well as NIHSS (p=0.007), ASPECTS (p=0.005), isolated M1/M2 occlusion (p=0.013), and age (p=0.032). The positive predictive value of f-CIS for a favorable outcome was 67%.Conclusionsf-CIS was strongly associated with a favorable outcome after MT of acute MCA occlusion. As an easy surrogate marker of cerebral perfusion, it may be a useful—albeit not sufficient—diagnostic test to select patients just before an MT or to manage them after recanalization.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Marie Luby ◽  
Zurab Nadareishvili ◽  
Kaylie Cullison ◽  
Richard T Benson ◽  
Amie W Hsia ◽  
...  

Purpose and Hypothesis: The ability to measure the immediate tissue effects in patients treated with thrombolysis ultra-early relative to their known onset has increased. We hypothesized that shorter onset to treatment times (OTT) would lead to more penumbra saved, calculated using multimodal MRI. Methods: Patients were included in this study if they met the following criteria: (1) were admitted between January 2010 and June 1, 2014 at one of two regional stroke centers, (2) had known last seen normal, acute MRI and IV tPA start times, (3) received an admit diagnosis of ischemic stroke, and (4) were treated with standard IV tPA. Penumbral volumes were calculated using the baseline MRI-defined mismatch regions minus the infarcted regions defined by the co-registered DWI at 24 hours. Patients were categorized to the “early” IV tPA cohort if their OTT was ≤ 120 minutes. Infarct growth was quantitatively defined as lesion volume increase > 5 mL from baseline DWI to 5-day FLAIR. Favorable clinical outcome was defined as discharge or later mRS < 2. Results: Sixty-three patients, 23 early- and 40 late-treated, were included in the study with mean age 75 (±15) years, 48% female, median [IQR]: admit NIHSS 10 [5-19], OTT 139 [109-185] minutes, baseline DWI volume 11.2mL [3.5-39.6], baseline MTT volume 120.9mL [37.8-220.7], and baseline mismatch volume 119.3mL [34.6-200.7]. Aside from time-based variables, only the amount of penumbra infarcted at 24 hours (p=0.015) was significantly different between the early- (9mL [1.7-19.7] and late-treated (2.4mL [0.7-7]) cohorts. The patients with favorable outcome were younger (p=0.012) with less severe admit NIHSS (p=0.026), smaller baseline DWI volume (p=0.017), smaller 24 hour DWI volume (p=0.041), and greater percentage of penumbra saved at 24 hours (p=0.010) but no difference in OTT (p=0.267). Using binomial logistic regression, percentage of penumbra saved at 24 hours (95%CI:0.000-0.011, p=0.010) was the only independent predictor of no infarct growth. Conclusions: This study establishes that significantly larger penumbral tissue saved at 24 hours, not early OTT, is predictive of both favorable clinical outcome and no infarct growth.


Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012858
Author(s):  
Hong fei Sang ◽  
Jun jie Yuan ◽  
Zhongming Qiu ◽  
Min Zhang ◽  
Xiao gang Hu ◽  
...  

Objective:To characterize the association of onset to puncture time (OPT) with clinical outcomes among patients with acute basilar artery occlusion receiving endovascular therapy (EVT) in clinical practice.Methods:Using the EVT for Acute Basilar Artery Occlusion (BASILAR) study, we identified consecutive patients with acute basilar artery occlusion receiving EVT in 47 comprehensive stroke centers in China from January 2014 to May 2019. The primary outcome was favorable functional outcome (defined as modified Rankin Scale score [mRS] 0–3) at 90 days. Secondary outcomes included function independence (mRS 0–2), mortality, and symptomatic intracerebral hemorrhage. The associations of OPT with clinical outcomes were analyzed using multivariable logistic regression (OPT as a categorical variable) and restricted cubic spline regression (OPT as a continuous variable).Results:Among 639 eligible patients, the median age was 65 years, and median OPT was 328 min (interquartile range, 220–490). Treatment within 4–8 hours and 8–12 hours were associated with lower rates of favorable outcome (adjusted OR, 0.63 [95% CI, 0.40–0.98] and 0.47 [95% CI, 0.23–0.93], respectively) compared with treatment within 4 hours. Restricted cubic spline regression analysis showed that the OPT had L-shaped associations with favorable outcome (Pnon-linearity=0.028) and functional independence (Pnon-linearity=0.025), with significant benefit loss throughout the first 9 hours but then appeared relatively flat. The odds of mortality increased relatively for OPT up to 9 hours, but then levelled off (Pnon-linearity=0.042). The association between symptomatic intracerebral hemorrhage and OPT was not significant.Conclusion:Among patients with acute basilar artery occlusion in routine practice, earlier treatment with EVT was associated with better outcomes throughout the first 9 hours after onset, but benefit may sustain unchanged afterwards.Classification of Evidence:This study provides Class II evidence that for patients with acute ischemic stroke due to basilar artery occlusion, earlier endovascular treatment is associated with better outcomes.


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