Study protocol for ACTIVE study:safety and feasibility evaluation of external ventricular drainage with ACTIVE fluid exchange in intraventricular hemorrhage-a phase 2, multi-center, randomized controlled trial

Background: Primary intraventricular hemorrhage (IVH) or IVH secondary to intracerebral (ICH) and subarachnoid hemorrhage (SAH) are known to have a very poor prognosis, with an expected mortality between 50 and 80% (Hinson et al. Current Neurology and Neuroscience Reports 10:73–82, 2010). Clearance of IVH might improve patient outcome. Methods: The study is designed as an investigator-initiated, comparative, prospective, multi-center, 1:1 randomized phase 2 trial evaluating the efficacy and safety of active irrigation in external ventricular drainage (intervention arm—IRRAflow) compared to passive external ventricular drainage (control arm—EVD). The trial will enroll 58 patients with primary or secondary IVH. Major eligibility criteria include age ≥18 years of age, IVH documented on head CT or MRI scan (Graeb score ≥3), need of cerebrospinal fluid drainage, deterioration of consciousness or medical sedation at the time of enrollment, and indication for active treatment evaluated by the treating physicians. Exclusion criteria included patients with fixed and dilated pupils and pregnant or nursing women. The primary endpoint of the study is catheter occlusion evaluated by time to first observed occlusion from VC placement. Secondary endpoints include clearance of ventricular blood as measured by head CT scan, rates of catheter-related infection and shunt dependency, length of intensive care unit stay, functional status—Extended Glascow Outcome Scale (eGOS) and modified Rankin scale (mRS) at discharge to rehabilitation and 90 days—and mortality rates at 30 days and 90 days. Discussion: With no standardized treatment for IVH and a poor prognosis, new treatments are needed. IVH patients often need CSF drainage to treat hydrocephalus and to decrease ICP. Standard treatment with passive external ventricular drainage is related to an increased risk of infections which is found in up to 22% of treated cases. The passive VC is known to have a risk of occlusion and is seen in 19–47% of the cases. We hypothesize that the use of active fluid change using the IRRAflow system will be safe and feasible and will reduce the occlusion and infection rates in patients with IVH. Trial registration: ClicalTrials.gov NCT05204849. Registered 15 December 2021.</p

Post-hoc analysis of outcome of intravenous thrombolysis in infarcts of infratentorial localization in the WAKE-UP trial

Introduction: In WAKE-UP (Efficacy and Safety of MRI-based Thrombolysis in Wake-Up Stroke), patients with an acute stroke of unknown onset time were randomized to treatment with intravenous alteplase or placebo, guided by MRI. Methods: In this exploratory post-hoc secondary analysis we compared clinical and imaging data, as well as treatment effects and safety of intravenous thrombolysis between patients with infra- vs supratentorial stroke. Results: Forty-eight out of 503 randomized patients (9.5%) presented with a stroke involving the cerebellum or brainstem. Patients with infratentorial stroke were younger compared to patients with supratentorial stroke (mean age 60 vs 66 years), more frequently male (85% vs 62%), and less severely affected (median NIHSS 4.5 vs 6.0). There was no heterogeneity for treatment effect between supratentorial (OR 1.67 95% CI 1.11 – 2.51) and infratentorial (OR 1.31 95% CI 0.41 – 4.22) sub-groups (test for interaction p=0.70). In patients with infratentorial stroke, favorable outcome (a score of 0-1 on the modified Rankin scale (mRS) at 90 days) was observed in 12/22 patients (54.5%) in the alteplase group and in 13/25 patients (52.0%) in the placebo group (p=0.59). The primary safety endpoint (death or mRS 4-6 at day 90) occurred in 3 patients of the alteplase group (13.6%) and 3 patients in the placebo group (12.0%); p=0.74. Discussion: WAKE-UP was underpowered for demonstrating treatment effect in subgroup analyses however, based on our current results, there is no evidence to recommend withholding MRI-guided thrombolysis in patients with unknown onset stroke of infratentorial localization

Prevalence and impact of SARS-CoV-2 infection among patients with acute ischaemic stroke: a nationwide register-based cohort study in Denmark

OBJECTIVES: An increased risk of stroke has been reported among patients with COVID-19 caused by SARS-CoV-2. We aimed to investigate the nationwide prevalence of SARS-CoV-2 among patients with acute ischaemic stroke and to study the impact on stroke severity, quality of care and mortality on an individual patient level.DESIGN: This was a nationwide register-based cohort study.SETTING: We used data from several Danish registers which were linked at an individual patient level using the unique civil registration number assigned to all Danish citizens. Patients were identified from the Danish Stroke Registry and information on SARS-CoV-2 infection status was collected from the Danish National COVID-19 Registry. Concurrent SARS-CoV-2 infection was defined as a positive PCR test within 31 days prior to, and 1 day after, stroke admission. Information on comorbidity was collected from the Danish National Patient Registry and information on vital status was collected from the Danish Civil Registration System.PARTICIPANTS: A total of 11 502 patients admitted with acute ischaemic stroke from 10 March 2020 to 31 May 2021 were included in the study.RESULTS: Among the included patients, the majority (84.6%) were tested for SARS-CoV-2, but only 68 had a positive test. These patients were more prone to have atrial fibrillation and were more often treated with reperfusion therapy. They had a significantly increased risk of severe stroke (adjusted relative risk (aRR) 1.93, 95% CI: 1.22 to 3.04) and a significantly increased 30-day mortality risk (aRR 2.29, 95% CI: 1.19 to 4.39). There was no difference in the proportion of patients fulfilling relevant performance measures on quality of care.CONCLUSION: In this nationwide study, only 0.6% of patients with acute ischaemic stroke were tested positive for a concurrent SARS-CoV-2 infection. The patients with SARS-CoV-2 presented with more severe strokes.</p

Abstract TP30: Effect of General Anesthesia versus Conscious Sedation on Achievement of Substantial Reperfusion for Different Target Occlusions - Analysis of the Goliath Randomized Trial

Background: Achievement of successful reperfusion during endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) may affected by patient motion, especially in more difficult to access, technically challenging targets, such as tandem and distal occlusions. General anesthesia (GA) may be particularly beneficial as compared to conscious sedation (CS) in such patients. Methods: We evaluated target occlusion subtypes in the GOLIATH randomized trial comparing GA and CS. Patients were divided in 2 groups based on target arterial occlusion: 1) single, proximal occlusion (ICA T/M1), and 2) tandem or distal (M2) occlusion. Technical success was defined as substantial reperfusion (TICI 2B/3). Clinical outcome measures at 90 days included disability level (mRS ordinal), functional independence (mRS 0-2), and mortality. Multivariable analysis adjusted for age, baseline NIHSS, baseline ischemic core volume, and IV TPA was conducted in each group to assess the impact on technical and clinical outcome. Interaction test for heterogeneity was conducted to assess the difference in outcomes across the subrgoups. Results: Among 128 analyzed patients, 80 (62.5%) had single, proximal occlusions and 48 (37.5%) had tandem (22.7%) or distal (14.8%). The absolute difference in substantial reperfusion was higher for both tandem occlusion (83.3% vs 36.4%) and distal occlusion (75% vs 57.1%) than for single, proximal occlusion (74.3% vs 66.7%). The combined distal and tandem occlusion group showed magnified reperfusion success with GA vs CS (80.0% vs 44.4%) compared with the single, proximal occlusion group, (p=0.048, interaction test for heterogeneity). The single and proximal occlusion group showed improved 3m functional independence with GA vs PS (p=0.030), although the heterogeneity between groups was not significant (proximal and single: 71.4% vs 44.4%; tandem or distal: 63.3% vs 72.2%, heterogeneity p=0.12). There was no heterogeneity in the effect of method of sedation on mortality across analyzed groups. Conclusions: Achievement of substantial reperfusion during endovascular thrombectomy may differentially be aided by general anesthesia in patients with technically more challenging distal and tandem occlusion

Effect of Remote Ischemic Conditioning in Ischemic Stroke Subtypes: A Post Hoc Subgroup Analysis From the RESIST Trial

BACKGROUND: Remote ischemic conditioning (RIC) is a simple and noninvasive procedure that has proved to be safe and feasible in numerous smaller clinical trials. Mixed results have been found in recent large randomized controlled trials. This is a post hoc subgroup analysis of the RESIST trial (Remote Ischemic Conditioning in Patients With Acute Stroke), investigating the effect of RIC in different acute ischemic stroke etiologies, and whether an effect was modified by treatment adherence.METHODS: Eligible patients were adults (aged ≥18 years), independent in activities of daily living, who had prehospital stroke symptoms with a duration of less than 4 hours. They were randomized to RIC or sham. The RIC treatment protocol consisted of 5 cycles with 5 minutes of cuff inflation alternating with 5 minutes with a deflated cuff. Acceptable treatment adherence was defined as when at least 80% of planned RIC cycles were received. The analysis was performed using the entire range (shift analysis) of the modified Rankin Scale (ordinal logistic regression).RESULTS: A total of 698 had acute ischemic stroke, 253 (36%) were women, and the median (interquartile range) age was 73 (63-80) years. Median (interquartile range) overall adherence to RIC/sham was 91% (68%-100%). In patients with a stroke due to cerebral small vessel disease, who were adherent to treatment, RIC was associated with improved functional outcome, and the odds ratio for a shift to a lower score on the modified Rankin Scale was 2.54 (1.03-6.25); P=0.042. The association remained significant after adjusting for potential confounders. No significant associations were found with other stroke etiologies, and the overall test for interaction was not statistically significant (χ2, 4.33, P=0.23).CONCLUSIONS: In patients with acute ischemic stroke due to cerebral small vessel disease, who maintained good treatment adherence, RIC was associated with improved functional outcomes at 90 days. These results should only serve as a hypothesis-generating for future trials.REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03481777.</p