Endovascular treatment to improve outcomes for medium vessel occlusions: The ESCAPE-MeVO trial.

Rationale: Clinical outcomes in acute ischemic stroke due to medium vessel occlusion (MeVO) are often poor when treated with best medical management. Data from non-randomized studies suggest that endovascular treatment (EVT) may improve outcomes in MeVO stroke, but randomized data on potential benefits and risks are hitherto lacking. Thus, there is insufficient evidence to guide EVT decision-making in MeVO stroke.

Assessing the efficacy and safety of hydroxychloroquine as outpatient treatment of COVID-19: a randomized controlled trial.

Background: Identification of therapies to prevent severe COVID-19 remains a priority. We sought to determine whether hydroxychloroquine treatment for outpatients with SARS-CoV-2 infection could prevent hospitalization, mechanical ventilation or death.

Methods: This randomized controlled trial was conducted in Alberta during the first wave of the COVID-19 pandemic without direct contact with participants.

Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial.

Background: Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in preclinical stroke models of ischaemia-reperfusion. In this trial, we assessed the efficacy and safety of nerinetide in human ischaemia-reperfusion that occurs with rapid endovascular thrombectomy in patients who had an acute ischaemic stroke.

Methods: For this multicentre, double-blind, randomised, placebo-controlled study done in 48 acute care hospitals in eight countries, we enrolled patients with acute ischaemic stroke due to large vessel occlusion within a 12 h treatment window.

Observed Cost and Variations in Short Term Cost-Effectiveness of Therapy for Ischemic Stroke in Interventional Management of Stroke (IMS) III.

Background: Examination of linked data on patient outcomes and cost of care may help identify areas where stroke care can be improved. We report on the association between variations in stroke severity, patient outcomes, cost, and treatment patterns observed over the acute hospital stay and through the 12-month follow-up for subjects receiving endovascular therapy compared to intravenous tissue plasminogen activator alone in the IMS (Interventional Management of Stroke) III Trial.

Methods And Results: Prospective data collected for a prespecified economic analysis of the trial were used.

Improving reperfusion time within the ESCAPE Endovascular Clinical Trial.

Introduction: Endovascular treatment of acute ischemic stroke is more effective when performed quickly. In this report, we describe quality interventions to ensure fast endovascular treatment times in the ESCAPE (Endovascular Treatment for Small Core and Anterior circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times) trial.

Methods: An "audit and feedback" intervention using webinar and letter was used to improve treatment time over the course of the trial.

Prolonged Activation of Invariant Natural Killer T Cells and T2-Skewed Immunity in Stroke Patients.

Background: Infection is highly prevalent and contribute significantly to mortality of stroke patients. In addition to the well described robust systemic lymphocytopenia and skewed T helper 2 (T2)-immunity after stroke, emerging experimental evidence demonstrate that the development of infection poststroke is attributed by the activation of invariant natural killer T (NKT) cells. In this prospective study, we examined the levels of a broad spectrum of inflammatory mediators, the activation status of NKT cell in the blood of patients with various degree of stroke severity, and investigate whether these parameters differ in patients who later develop poststroke infections.

Endovascular Therapy Is Effective and Safe for Patients With Severe Ischemic Stroke: Pooled Analysis of Interventional Management of Stroke III and Multicenter Randomized Clinical Trial of Endovascular Therapy for Acute Ischemic Stroke in the Netherlands Data.

Background And Purpose: We assessed the effect of endovascular treatment in acute ischemic stroke patients with severe neurological deficit (National Institutes of Health Stroke Scale score, ≥20) after a prespecified analysis plan.

Methods: The pooled analysis of the Interventional Management of Stroke III (IMS III) and Multicenter Randomized Clinical Trial of Endovascular Therapy for Acute Ischemic Stroke in the Netherlands (MR CLEAN) trials included participants with an National Institutes of Health Stroke Scale score of ≥20 before intravenous tissue-type plasminogen activator (tPA) treatment (IMS III) or randomization (MR CLEAN) who were treated with intravenous tPA ≤3 hours of stroke onset. Our hypothesis was that participants with severe stroke randomized to endovascular therapy after intravenous tPA would have improved 90-day outcome (distribution of modified Rankin Scale scores), when compared with those who received intravenous tPA alone.

Albumin Administration in Acute Ischemic Stroke: Safety Analysis of the ALIAS Part 2 Multicenter Trial.

Background: Albumin treatment of ischemic stroke was associated with cardiopulmonary adverse events in previous studies and a low incidence of intracranial hemorrhage. We sought to describe the neurological and cardiopulmonary adverse events in the ALIAS Part 2 Multicenter Trial.

Methods: Ischemic stroke patients, aged 18-83 and a baseline NIHSS ≥ 6, were randomized to treatment with ALB or saline control within 5 hours of stroke onset.

Twelve-Month Clinical and Quality-of-Life Outcomes in the Interventional Management of Stroke III Trial.

Background And Purpose: Randomized trials have indicated a benefit for endovascular therapy in appropriately selected stroke patients at 3 months, but data regarding outcomes at 12 months are currently lacking.

Methods: We compared functional and quality-of-life outcomes at 12 months overall and by stroke severity in stroke patients treated with intravenous tissue-type plasminogen activator followed by endovascular treatment as compared with intravenous tissue-type plasminogen activator alone in the Interventional Management of Stroke III Trial. The key outcome measures were a modified Rankin Scale score ≤2 (functional independence) and the Euro-QoL EQ-5D, a health-related quality-of-life measure.

Randomized assessment of rapid endovascular treatment of ischemic stroke.

Background: Among patients with a proximal vessel occlusion in the anterior circulation, 60 to 80% of patients die within 90 days after stroke onset or do not regain functional independence despite alteplase treatment. We evaluated rapid endovascular treatment in addition to standard care in patients with acute ischemic stroke with a small infarct core, a proximal intracranial arterial occlusion, and moderate-to-good collateral circulation.

Methods: We randomly assigned participants to receive standard care (control group) or standard care plus endovascular treatment with the use of available thrombectomy devices (intervention group).

Endovascular treatment for Small Core and Anterior circulation Proximal occlusion with Emphasis on minimizing CT to recanalization times (ESCAPE) trial: methodology.

ESCAPE is a prospective, multicenter, randomized clinical trial that will enroll subjects with the following main inclusion criteria: less than 12 h from symptom onset, age > 18, baseline NIHSS >5, ASPECTS score of >5 and CTA evidence of carotid T/L or M1 segment MCA occlusion, and at least moderate collaterals by CTA. The trial will determine if endovascular treatment will result in higher rates of favorable outcome compared with standard medical therapy alone. Patient populations that are eligible include those receiving IV tPA, tPA ineligible and unwitnessed onset or wake up strokes with 12 h of last seen normal.

Advance care planning in stroke: influence of time on engagement in the process.

Purpose: Individuals who experience stroke have a higher likelihood of subsequent stroke events, making it imperative to plan for future medical care. In the event of a further serious health event, engaging in the process of advanced care planning (ACP) can help family members and health care professionals (HCPs) make medical decisions for individuals who have lost the capacity to do so. Few studies have explored the views and experiences of patients with stroke about discussing their wishes and preferences for future medical events, and the extent to which stroke HCPs engage in conversations around planning for such events.

High-dose albumin treatment for acute ischaemic stroke (ALIAS) Part 2: a randomised, double-blind, phase 3, placebo-controlled trial.

Background: In animal models of ischaemic stroke, 25% albumin reduced brain infarction and improved neurobehavioural outcome. In a pilot clinical trial, albumin doses as high as 2 g/kg were safely tolerated. We aimed to assess whether albumin given within 5 h of the onset of acute ischaemic stroke increased the proportion of patients with a favourable outcome.

Endovascular therapy after intravenous t-PA versus t-PA alone for stroke.

Background: Endovascular therapy is increasingly used after the administration of intravenous tissue plasminogen activator (t-PA) for patients with moderate-to-severe acute ischemic stroke, but whether a combined approach is more effective than intravenous t-PA alone is uncertain.

Methods: We randomly assigned eligible patients who had received intravenous t-PA within 3 hours after symptom onset to receive additional endovascular therapy or intravenous t-PA alone, in a 2:1 ratio. The primary outcome measure was a modified Rankin scale score of 2 or less (indicating functional independence) at 90 days (scores range from 0 to 6, with higher scores indicating greater disability).

The Albumin in Acute Stroke Part 1 Trial: an exploratory efficacy analysis.

Background And Purpose: The Albumin in Acute Stroke (ALIAS) Part 2 Trial is directly testing whether 2 g/kg of 25% human albumin (ALB) administered intravenously within 5 hours of ischemic stroke onset results in improved clinical outcome. Recruitment into Part 1 of the ALIAS Trial was halted for safety reasons. ALIAS Part 2 is a new, reformulated trial with more-stringent exclusion criteria.

The albumin in acute stroke (ALIAS) multicenter clinical trial: safety analysis of part 1 and rationale and design of part 2.

Background And Purpose: enrollment in the Albumin in Acute Stroke (ALIAS) Trial was suspended in late 2007 due to a safety concern. We present the safety data of that Trial ("Part 1") and the rationale for the design of Part 2.

Methods: ALIAS Part 1 was designed to assess whether 25% albumin (ALB) started within 5 hours of stroke onset would confer neuroprotection in subjects with acute ischemic stroke and baseline National Institutes of Health Stroke Scale of ≥ 6.

The beta-hCG+erythropoietin in acute stroke (BETAS) study: a 3-center, single-dose, open-label, noncontrolled, phase IIa safety trial.

Background And Purpose: Animal data suggest the use of beta-human chorionic gonadotropin followed by erythropoietin to promote brain repair after stroke. The current study directly translated these results by evaluating safety of this sequential growth factor therapy through a 3-center, single-dose, open-label, noncontrolled, Phase IIa trial.

Methods: Patients with ischemic stroke 24 to 48 hours old and National Institutes of Health Stroke Scale score of 6 to 24 started a 9-day course of beta-human chorionic gonadotropin (once daily on Days 1, 3, and 5 of study participation) followed by erythropoietin (once daily on Days 7, 8, and 9 of study participation).

Methodology of the Interventional Management of Stroke III Trial.

Rationale: The Interventional Management of Stroke (IMS) I and II pilot trials demonstrated that the combined intravenous (i.v.) and intraarterial (i.

The albumin in acute stroke trial (ALIAS); design and methodology.

Unlabelled: Stroke is a serious global illness. Human albumin has emerged as a putative therapy for ischaemic stroke based on strong evidence from animal models. Following confirmation of the safety and feasibility of high-dose albumin treatment for acute ischaemic stroke in a pilot study, the Albumin in Acute Stroke trial, a phase 3 randomised, double-blinded, placebo-controlled clinical trial was initiated to evaluate the efficacy of high-dose albumin compared to saline control within 5 h of ischaemic stroke onset.

Fast assessment of stroke and transient ischaemic attack to prevent early recurrence (FASTER): a randomised controlled pilot trial.

Background: Patients with transient ischaemic attack (TIA) or minor stroke are at high immediate risk of stroke. The optimum early treatment options for these patients are not known.

Methods: Within 24 h of symptom onset, we randomly assigned, in a factorial design, 392 patients with TIA or minor stroke to clopidogrel (300 mg loading dose then 75 mg daily; 198 patients) or placebo (194 patients), and simvastatin (40 mg daily; 199 patients) or placebo (193 patients).

The ALIAS Pilot Trial: a dose-escalation and safety study of albumin therapy for acute ischemic stroke--I: Physiological responses and safety results.

Background And Purpose: In preclinical stroke models, high-dose human albumin confers robust neuroprotection. We investigated the safety and tolerability of this therapy in patients with acute ischemic stroke.

Methods: The ALIAS (Albumin in Acute Stroke) Pilot Clinical Trial used a multiple-tier, open-label, dose-escalation design.

The ALIAS Pilot Trial: a dose-escalation and safety study of albumin therapy for acute ischemic stroke--II: neurologic outcome and efficacy analysis.

Background And Purpose: High-dose human albumin (ALB) is robustly neuroprotective in rodent stroke models. A phase I dose-escalation study was conducted to assess the safety of ALB therapy in ischemic stroke. We analyzed the data for preliminary evidence of treatment efficacy.

Acute intravenous--intra-arterial revascularization therapy for severe ischemic stroke.

Background: Intravenous alteplase for acute ischemic stroke is least efficacious for patients with proximal large-artery occlusions and clinically severe strokes. Intra-arterial therapy has the theoretical advantage of establishing a neurovascular diagnosis and high symptomatic artery patency rate but the disadvantage of requiring extra time and technical expertise. A combination of these two approaches may provide the best chance of improving outcome in severe acute ischemic stroke.