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Background: In the SPOTLIGHT trial (Spot Sign Selection of Intracerebral Hemorrhage to Guide Hemostatic Therapy), patients with a computed tomography (CT) angiography spot-sign positive acute intracerebral hemorrhage were randomized to rFVIIa (recombinant activated factor VIIa; 80 μg/kg) or placebo within 6 hours of onset, aiming to limit hematoma expansion. Administration of rFVIIa did not significantly reduce hematoma expansion. In this prespecified analysis, we aimed to investigate the impact of delays from baseline imaging to study drug administration on hematoma expansion. Methods: Hematoma volumes were measured on the baseline CT, early post-dose CT, and 24 hours CT scans. Total hematoma volume (intracerebral hemorrhage+intraventricular hemorrhage) change between the 3 scans was calculated as an estimate of how much hematoma expansion occurred before and after studying drug administration. Results: Of the 50 patients included in the trial, 44 had an early post-dose CT scan. Median time (interquartile range) from onset to baseline CT was 1.4 hours (1.2–2.6). Median time from baseline CT to study drug was 62.5 (55–80) minutes, and from study drug to early post-dose CT was 19 (14.5–30) minutes. Median (interquartile range) total hematoma volume increased from baseline CT to early post-dose CT by 10.0 mL (−0.7 to 18.5) in the rFVIIa arm and 5.4 mL (1.8–8.3) in the placebo arm ( P =0.96). Median volume change between the early post-dose CT and follow-up scan was 0.6 mL (−2.6 to 8.3) in the rFVIIa arm and 0.7 mL (−1.6 to 2.1) in the placebo arm ( P =0.98). Total hematoma volume decreased between the early post-dose CT and 24-hour scan in 44.2% of cases (rFVIIa 38.9% and placebo 48%). The adjusted hematoma growth in volume immediately post dose for FVIIa was 0.998 times that of placebo ([95% CI, 0.71–1.43]; P =0.99). The hourly growth in FFVIIa was 0.998 times that for placebo ([95% CI, 0.994–1.003]; P =0.50; Table 3). Conclusions: In the SPOTLIGHT trial, the adjusted hematoma volume growth was not associated with Factor VIIa treatment. Most hematoma expansion occurred between the baseline CT and the early post-dose CT, limiting any potential treatment effect of hemostatic therapy. Future hemostatic trials must treat intracerebral hemorrhage patients earlier from onset, with minimal delay between baseline CT and drug administration. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01359202.

Intravenous thrombolysis with alteplase bolus followed by infusion is a global standard of care for patients with acute ischaemic stroke. We aimed to determine whether tenecteplase given as a single bolus might increase reperfusion compared with this standard of care.In this multicentre, open-label, parallel-group, registry-linked, randomised, controlled trial (AcT), patients were enrolled from 22 primary and comprehensive stroke centres across Canada. Patients were eligible for inclusion if they were aged 18 years or older, with a diagnosis of ischaemic stroke causing disabling neurological deficit, presenting within 4·5 h of symptom onset, and eligible for thrombolysis per Canadian guidelines. Eligible patients were randomly assigned (1:1), using a previously validated minimal sufficient balance algorithm to balance allocation by site and a secure real-time web-based server, to either intravenous tenecteplase (0·25 mg/kg to a maximum of 25 mg) or alteplase (0·9 mg/kg to a maximum of 90mg; 0·09 mg/kg as a bolus and then a 60 min infusion of the remaining 0·81 mg/kg). The primary outcome was the proportion of patients who had a modified Rankin Scale (mRS) score of 0-1 at 90-120 days after treatment, assessed via blinded review in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment who did not withdraw consent). Non-inferiority was met if the lower 95% CI of the difference in the proportion of patients who met the primary outcome between the tenecteplase and alteplase groups was more than -5%. Safety was assessed in all patients who received any of either thrombolytic agent and who were reported as treated. The trial is registered with ClinicalTrials.gov, NCT03889249, and is closed to accrual.Between Dec 10, 2019, and Jan 25, 2022, 1600 patients were enrolled and randomly assigned to tenecteplase (n=816) or alteplase (n=784), of whom 1577 were included in the ITT population (n=806 tenecteplase; n=771 alteplase). The median age was 74 years (IQR 63-83), 755 (47·9%) of 1577 patients were female and 822 (52·1%) were male. As of data cutoff (Jan 21, 2022), 296 (36·9%) of 802 patients in the tenecteplase group and 266 (34·8%) of 765 in the alteplase group had an mRS score of 0-1 at 90-120 days (unadjusted risk difference 2·1% [95% CI - 2·6 to 6·9], meeting the prespecified non-inferiority threshold). In safety analyses, 27 (3·4%) of 800 patients in the tenecteplase group and 24 (3·2%) of 763 in the alteplase group had 24 h symptomatic intracerebral haemorrhage and 122 (15·3%) of 796 and 117 (15·4%) of 763 died within 90 days of starting treatment INTERPRETATION: Intravenous tenecteplase (0·25 mg/kg) is a reasonable alternative to alteplase for all patients presenting with acute ischaemic stroke who meet standard criteria for thrombolysis.Canadian Institutes of Health Research, Alberta Strategy for Patient Oriented Research Support Unit.

Alteplase is an effective treatment for ischaemic stroke patients, and it is widely available at all primary stroke centres. The effectiveness of alteplase is highly time-dependent. Large tertiary centres have reported significant improvements in their door-to-needle (DTN) times. However, these same improvements have not been reported at community hospitals.Red Deer Regional Hospital Centre (RDRHC) is a community hospital of 370 beds that serves approximately 150,000 people in their acute stroke catchment area. The RDRHC participated in a provincial DTN improvement initiative, and implemented a streamlined algorithm for the treatment of stroke patients. During this intervention period, they implemented the following changes: early alert of an incoming acute stroke patient to the neurologist and care team, meeting the patient immediately upon arrival, parallel work processes, keeping the patient on the Emergency Medical Service stretcher to the CT scanner, and administering alteplase in the imaging area. Door-to-needle data were collected from July 2007 to December 2017.A total of 289 patients were treated from July 2007 to December 2017. In the pre-intervention period, 165 patients received alteplase and the median DTN time was 77 minutes [interquartile range (IQR): 60-103 minutes]; in the post-intervention period, 104 patients received alteplase and the median DTN time was 30 minutes (IQR: 22-42 minutes) (plt; 0.001). The annual number of patients that received alteplase increased from 9 to 29 in the pre-intervention period to annual numbers of 41 to 63 patients in the post-intervention period.Community hospitals staffed with community neurologists can achieve median DTN times of 30 minutes or less.L’altéplase est un traitement efficace dans le cas de patients victimes d’AVC ischémiques et demeure largement disponible dans les centres de soins de niveau primaire dédiés aux AVC. Cela dit, son efficacité dépend fortement des délais en fonction desquels on peut l’administrer. À cet égard, les centres de soins de niveau tertiaire ont fait état d’importantes améliorations en ce qui regarde leurs délais entre l’arrivée de patients et l’injection d’un traitement thrombolytique. Toutefois, il semble que de telles améliorations n’ont pas été signalées dans les hôpitaux communautaires.Le Red Deer Regional Hospital Centre (RDRHC) est un hôpital communautaire de 370 lits qui dessert approximativement 150 000 personnes dans sa zone d’attraction. Cet hôpital a participé à une initiative provinciale de réduction des délais mentionnés ci-dessus. Pour ce faire, il a mis au point un algorithme simplifié en vue du traitement de patients victimes d’AVC. Au cours de cette période d’intervention, les mesures de changement suivantes ont donc été adoptées : des alertes précoces transmises à un neurologue et aux équipes soignantes au moment de l’admission de patients victimes d’AVC aigus ; des rencontres immédiates avec les patients, et ce, dès leur arrivée à l’hôpital ; des processus de travail menés de façon parallèle ; le maintien des patients dans une civière d’ambulance jusqu’à temps qu’on puisse les conduire à un tomodensitomètre ; enfin, le fait d’administrer l’altéplase en fonction de la zone atteinte révélée par imagerie. Soulignons enfin que nos données en matière de réduction des délais ont été collectées de juillet 2007 à décembre 2017.Au total, 289 patients ont été traités durant cette période. Au cours de la période antérieure à l’initiative évoquée précédemment, 165 patients ont bénéficié d’un traitement à l’altéplase ; les délais médians entre l’arrivée des patients et l’injection de ce médicament thrombolytique étaient alors de 77 minutes (EI : 60-103 minutes). Une fois mise en place l’initiative de réduction des délais, 104 patients ont reçu un traitement à l’altéplase ; cette fois, les délais médians du RDRHC étaient de 30 minutes (EI : 22-42 minutes ; p0,001). Fait à noter, le nombre annuel de patients ayant bénéficié de l’altéplase est passé de 9 à 29 durant la période pré-initiative et de 41 à 63 lors de la période post-initiative.Dans le cas des hôpitaux communautaires disposant de neurologues réguliers, il est possible de parvenir à des délais de 30 minutes ou moins entre l’arrivée de patients et l’injection d’un traitement thrombolytique.

Background: The assortment of patients based on the underlying pathophysiology is central to preventing recurrent stroke after a transient ischemic attack and minor stroke (TIA-MS). The causative classification of stroke (CCS) and the A-S-C-O (A for atherosclerosis, S for small vessel disease, C for Cardiac source, O for other cause) classification schemes have recently been developed. These systems have not been specifically applied to the TIA-MS population. We hypothesized that both CCS and A-S-C-O would increase the proportion of patients with a definitive etiologic mechanism for TIA-MS as compared with TOAST. Methods: Patients were analyzed from the CATCH study. A single-stroke physician assigned all patients to an etiologic subtype using published algorithms for TOAST, CCS and ASCO. We compared the proportions in the various categories for each classification scheme and then the association with stroke progression or recurrence was assessed. Results: TOAST, CCS and A-S-C-O classification schemes were applied in 469 TIA-MS patients. When compared to TOAST both CCS (58.0 vs. 65.3%; p < 0.0001) and ASCO grade 1 or 2 (37.5 vs. 65.3%; p < 0.0001) assigned fewer patients as cause undetermined. CCS had increased assignment of cardioembolism (+3.8%, p = 0.0001) as compared with TOAST. ASCO grade 1 or 2 had increased assignment of cardioembolism (+8.5%, p < 0.0001), large artery atherosclerosis (+14.9%, p < 0.0001) and small artery occlusion (+4.3%, p < 0.0001) as compared with TOAST. Compared with CCS, using ASCO resulted in a 20.5% absolute reduction in patients assigned to the ‘cause undetermined' category (p < 0.0001). Patients who had multiple high-risk etiologies either by CCS or ASCO classification or an ASCO undetermined classification had a higher chance of having a recurrent event. Conclusion: Both CCS and ASCO schemes reduce the proportion of TIA and minor stroke patients classified as ‘cause undetermined.' ASCO resulted in the fewest patients classified as cause undetermined. Stroke recurrence after TIA-MS is highest in patients with multiple high-risk etiologies or cryptogenic stroke classified by ASCO.

Background: classification of Transient Ischemic attacks (TIA) and minor stroke is challenging, as there is no classification systems developed specifically for the TIA and minor stroke patient population. Hypothesis: We hypothesize that the newly developed Causative Classification System (CCS) and the Atherosclerosis Small Vessel Disease Cardiac Source Other Source (ASCO) classification would reduce the proportion of patients classified as cause undetermined compared with The Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification in a large prospectively evaluated TIA and Minor stroke population. Methods: Using published algorithms for TOAST, CCS, and ASCO, a single rater classified the etiology in patients presenting with a high-risk TIA (weakness or speech disturbance lasting ≥ 5minutes) or minor ischemic stroke (National Institute of Health Stroke Scale score ≤ 3) who underwent CT/CTA and subsequent MRI as part of the CATCH study. Results: 419 patients with TIA or Minor stroke were classified using TOAST, CCS, and ASCO. The proportion of patients with an undetermined etiology was 51.3% (215/419) with TOAST. This was significantly reduced by both CCS 36% (151/419, p< 0.001) and ASCO 41% (172/419, p< 0.001). CCS was also less likely to have an undetermined etiology as compared to ASCO (36% versus 41%, p = 0.024). When compared with TOAST, there was a 23.9% (95%CI:18.1- 29.7, P< 0.001) and 17.4% (10.1- 24.7, P< 0.001) reduction in the proportion of patients assigned to the undetermined group using CCS and ASCO respectively. The 8.5 % reduction in the undetermined group between CCS and ASCO was also statistically different P=0.031). Compared with ASCO1, CCS increased the assignment of patients to large artery disease (relative increase 7.4% {4.3-10.4}, P< 0.001) and Cardio-embolism/cardio-aortic categories (relative increase 8.1% {4.6-11.5}, P< 0.001). Conclusions: Both CCS and ASCO were superior to TOAST in assigning fewer patients to an undetermined etiology category. CCS was superior to ASCO at reducing the proportion of patients with undetermined etiology. This was largely driven by increased assignment in the large artery and Cardio-aorto embolic categories.