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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.

Introduction: First-pass effect (FPE), i.e., achieving reperfusion with a single thrombectomy device pass, is associated with better clinical outcomes in patients with acute stroke. FPE is therefore increasingly being used as a marker of device and procedural efficacy. We evaluated the ability of thrombus-based radiomics models to predict FPE in patients undergoing endovascular thrombectomy (EVT) and compare performance to experts and non-radiomics thrombus characteristics. Methods: Patients with thin-slice non-contrast CT and CT angiography from The Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke (ESCAPE-NA1) trial were included. Thrombi were manually segmented on all images. Data was randomly split into a derivation set that included a training and a validation subset and an independent test set. Radiomics features were extracted from the derivation data set. Three expert stroke physicians reviewed baseline imaging and clinical data for the test set. The machine learning (ML) models were compared to the three experts in predicting the primary outcome (FPE) in the test set using area under the receiver operating characteristic curves (AUC-ROC). Results: A total of 554 patients with available thin-slice images comprised of a derivation set (training subset [n=388, 70%]), validation subset [n=55, 10%]), and a test set (n=111, 20%). FPE was seen in 31.8% in the derivation set and 31.5 % in the test set. AUC of the best radiomics model was 0.74 (95% CI: 0.64, 0.84), which was higher than the mean AUC of the three experts 0.60 (95% CI: 0.50, 0.71) ( P =0.009). Specificity of radiomics was better than the mean specificity of the three experts, 46 of 76 (60%) vs. 35 of 76 (46.4%), P =0.004, whereas sensitivity was not significantly different between radiomics (28 of 35 [79%]) and experts (27 of 35 [77%]). Moreover, radiomics features performed better than non-radiomics features such as thrombus volume and permeability measurements in predicting FPE ( P Conclusion: A radiomics-based ML model of thrombus characteristics on non-contrast CT and CT angiography performs better than experts and non-radiomics image characteristics in predicting FPE in patients with acute stroke treated with EVT.

Background: Until recently, clinical benefits of endovascular stroke treatment remained unproven. Care trials can be used to simultaneously offer yet-to-be validated interventions and verify treatment outcomes. Our aim was to implement care trial methodology for patients with severe acute ischemic stroke. Methods: The study was offered to all patients considered for endovascular management of acute ischemic stroke in one Canadian hospital. Inclusion criteria were broad: onset of symptoms ≤ 5h or at any time in the presence of clinical-imaging mismatch; suspected anterior or posterior circulation large vessel occlusion; patients eligible or ineligible for intravenous thrombolysis. Exclusion criteria were few: established infarction or hemorrhagic transformation of the target symptomatic territory; poor 3-month prognosis from comorbidities. The primary outcome was mRS ≤ 2 at three months. Patients were randomly allocated to standard care (control) or standard care plus endovascular treatment (intervention group). Analyses were by intention-to-treat. (Identifier NCT02157532) Findings: Seventy-seven patients were recruited in 19 months (March 2013 - October 2014) at a single center. Randomized allocation was interrupted when other trials showed the benefits of endovascular therapy. At three months, 20 of 40 patients (50·0 %; 95% C.I.: 35%-65%) in the intervention group had reached the primary outcome, compared to 14 of 37 patients (37·8%; 95% C.I.: 24%-54%) in the control group arm (P=0·36). Eleven patients in the intervention arm died within 3 months compared to 9 patients in the standard care arm. Interpretation: EASI met all the characteristics of a care trial: inclusion of all eligible patients, no extra risk, no extra test, no extra cost, simple case report forms filled by care personnel, normal follow-up, involvement of all regular practitioners, and flexible care. The trial was prematurely interrupted, but this approach offers a promising means to manage clinical dilemmas and guide uncertain practices in the care of patients. Funding: There was no funding source for this study.