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Safety of intravenous alteplase within 4.5 hours for patients awakening with stroke symptoms.

ABSTRACT: BACKGROUND:Up to 25% of acute stroke patients first note symptoms upon awakening. We hypothesized that patients awaking with stroke symptoms may be safely treated with intravenous alteplase (IV tPA) using non-contrast head CT (NCHCT), if they meet all other standard criteria. METHODS:The SAfety of Intravenous thromboLytics in stroke ON awakening (SAIL ON) was a prospective, open-label, single treatment arm, pilot safety trial of standard dose IV tPA in patients who presented with stroke symptoms within 0-4.5 hours of awakening. From January 30, 2013, to September 1, 2015, twenty consecutive wakeup stroke patients selected by NCHCT were enrolled. The primary outcome was symptomatic intracerebral hemorrhage (sICH) in the first 36 hours. Secondary outcomes included NIH stroke scale (NIHSS) at 24 hours; and modified Rankin Score (mRS), NIHSS, and Barthel index at 90 days. RESULTS:The average age was 65 years (range 47-83); 40% were women; 50% were African American. The average NIHSS was 6 (range 4-11). The average time from wake-up to IV tPA was 205 minutes (range 114-270). The average time from last known well to IV tPA was 580 minutes (range 353-876). The median mRS at 90 days was 1 (range 0-5). No patients had sICH; two of 20 (10%) had asymptomatic ICH on routine post IV tPA brain imaging. CONCLUSIONS:Administration of IV tPA was feasible and may be safe in wakeup stroke patients presenting within 4.5 hours from awakening, screened with NCHCT. An adequately powered randomized clinical trial is needed. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov NCT01643902.

SUBMITTER: Urrutia VC

PROVIDER: S-EPMC5963768 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Safety of intravenous alteplase within 4.5 hours for patients awakening with stroke symptoms.

Urrutia Victor C VC Faigle Roland R Zeiler Steven R SR Marsh Elisabeth B EB Bahouth Mona M Cerdan Trevino Mario M Dearborn Jennifer J Leigh Richard R Rice Susan S Lane Karen K Saheed Mustapha M Hill Peter P Llinas Rafael H RH

PloS one 20180522 5

<h4>Background</h4>Up to 25% of acute stroke patients first note symptoms upon awakening. We hypothesized that patients awaking with stroke symptoms may be safely treated with intravenous alteplase (IV tPA) using non-contrast head CT (NCHCT), if they meet all other standard criteria.<h4>Methods</h4>The SAfety of Intravenous thromboLytics in stroke ON awakening (SAIL ON) was a prospective, open-label, single treatment arm, pilot safety trial of standard dose IV tPA in patients who presented with ...[more]

PMID: 29787575

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Project description:OBJECTIVES:Alteplase is commonly recommended for acute ischaemic stroke within 4.5?hours after stroke onset. The Third European Cooperative Acute Stroke Study (ECASS III) is the only trial reporting statistically significant efficacy for clinical outcomes for alteplase use 3-4.5?hours after stroke onset. However, baseline imbalances in history of prior stroke and stroke severity score may confound this apparent finding of efficacy. We reanalysed the ECASS III trial data adjusting for baseline imbalances to determine the robustness or sensitivity of the efficacy estimates. DESIGN:Reanalysis of randomised placebo-controlled trial. We obtained access to the ECASS III trial data and replicated the previously reported analyses to confirm our understanding of the data. We adjusted for baseline imbalances using multivariable analyses and stratified analyses and performed sensitivity analysis for missing data. SETTING:Emergency care. PARTICIPANTS:821 adults with acute ischaemic stroke who could be treated 3-4.5?hours after symptom onset. INTERVENTIONS:Intravenous alteplase (0.9?mg/kg of body weight) or placebo. MAIN OUTCOME MEASURES:The original primary efficacy outcome was modified Rankin Scale (mRS) score 0 or 1 (ie, being alive without any disability) and the original secondary efficacy outcome was a global outcome based on a composite of functional end points, both at 90 days. Adjusted analyses were only reported for the primary efficacy outcome and the original study protocol did not specify methods for adjusted analyses. Our adjusted reanalysis included these outcomes, symptom-free status (mRS 0), dependence-free status (mRS 0-2), mortality (mRS 6) and change across the mRS 0-6 spectrum at 90 days; and mortality and symptomatic intracranial haemorrhage at 7 days. RESULTS:We replicated previously reported unadjusted analyses but discovered they were based on a modified interpretation of the National Institutes of Health Stroke Scale (NIHSS) score. The secondary efficacy outcome was no longer significant using the original NIHSS score. Previously reported adjusted analyses could only be replicated with significant effects for the primary efficacy outcome by using statistical approaches not reported in the trial protocol or statistical analysis plan. In analyses adjusting for baseline imbalances, all efficacy outcomes were not significant, but increases in symptomatic intracranial haemorrhage remained significant. CONCLUSIONS:Reanalysis of the ECASS III trial data with multiple approaches adjusting for baseline imbalances does not support any significant benefits and continues to support harms for the use of alteplase 3-4.5?hours after stroke onset. Clinicians, patients and policymakers should reconsider interpretations and decisions regarding management of acute ischaemic stroke that were based on ECASS III results. TRIAL REGISTRATION NUMBER:NCT00153036.

Project description:Background and Purpose- American Heart Association guidelines recommend obtaining baseline troponin in all patients with acute ischemic stroke. Yet, there is a paucity of data on the prevalence of baseline troponin elevation and specifically its diagnostic yield for acute myocardial infarction (AMI) in patients presenting within the time window for thrombolysis. Methods- We retrospectively analyzed 1072 consecutive patients admitted for acute ischemic stroke or transient ischemic attack, who presented within 4.5 hours of last known well (LKW). Patients who had baseline cardiac troponin I (bcTnI) obtained within 72 hours from LKW (n=525) were included in the study. Multivariable logistic regression was conducted to determine factors independently related to an elevated bcTnI (>0.04 ng/mL). We calculated the area under receiver operator curves, sensitivity, and specificity, to determine the diagnostic accuracy of (i) the bcTnI for AMI stratified by the time to assessment and (ii) the best time cutoff for obtaining bcTnI. Results- Among included subjects, the median time from LKW to the bcTnI was 3.8 hours and 113 (21.5%) subjects had an elevated bcTnI. Assessment of bcTnI within 4.5 hours from LKW was significantly more often associated with normal values as compared to assessment between 4.5 and 72 hours (61.7% versus 38.3%; P=0.001). Fifteen (2.9%) patients were diagnosed with AMI. After adjustment for pertinent confounders, time to bcTnI assessment was independently associated with AMI (odds ratio, 1.04 [95% CI, 1.02-1.07] P=0.001). When stratified by time, bcTnI assessed within 4.5 hours had a sensitivity of 25% and specificity of 83.7% for AMI, whereas bcTnI assessment between 4.5 and 72 hours was associated with a sensitivity of 90.9% and specificity of 74.8%. Conclusions- Assessment of bcTnI after 4.5 hours from LKW was associated with greater diagnostic accuracy than testing within 4.5 hours. This information may inform routine clinical practice.

Project description:Background and purposeWith increasing use of endovascular therapy, physicians' attitudes toward intravenous alteplase in endovascular therapy-eligible patients may be changing. We explored current intravenous alteplase treatment practices of physicians in endovascular therapy- and alteplase-eligible patients with acute stroke using prespecified case scenarios and compared how their current local treatment practices differ compared with an assumed ideal environment.Materials and methodsIn an international multidisciplinary survey, 607 physicians involved in acute stroke care were randomly assigned 10 of 22 case scenarios, among them 14 with guideline-based alteplase recommendations (9 with level 1A and 5 with level 2B recommendation) and were asked how they would treat the patient: A) under their current local resources, and B) under assumed ideal conditions. Answer options were the following: 1) anticoagulation/antiplatelet therapy, 2) endovascular therapy, 3) endovascular therapy plus intravenous alteplase, and 4) intravenous alteplase. Decision rates were calculated, and multivariable regression analysis was performed to determine variables associated with the decision to abandon intravenous alteplase.ResultsIn cases with guideline recommendations for alteplase, physicians favored alteplase in 82.0% under current local resources and in 79.3% under assumed ideal conditions (P < .001). Under assumed ideal conditions, interventional neuroradiologists would refrain from intravenous alteplase most often (6.28%, OR = 2.40; 95% CI, 1.01-5.71). When physicians' current and ideal decisions differed, most would like to add endovascular therapy to intravenous alteplase in an ideal setting (196/3861 responses, 5.1%).ConclusionsIn patients eligible for endovascular therapy and intravenous alteplase, we observed a slightly lower decision rate in favor of intravenous alteplase under assumed ideal conditions compared with the decision rate under current local resources.

Project description:Background and purposeIn spite of the advent of thrombolytic therapy, CT-perfusion imaging is currently not fully used for clinical decision-making and not included in published clinical guidelines for management of ischemic stroke. We investigated whether lesion volumes on cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) maps predict final infarct volume and whether all these parameters are needed for triage to intravenous recombinant tissue plasminogen activator (rtPA). We also investigated the effect of intravenous rtPA on affected brain by measuring salvaged tissue volume in patients receiving intravenous rtPA and in controls.Materials and methodsForty-four patients receiving intravenous rtPA and 19 controls underwent CT perfusion (CTP) studies in the emergency department within 3 hours of stroke onset. Lesion volumes were measured on MTT, CBV, and CBF maps by region-of-interest analysis and were compared with follow-up CT volumes by correlation and regression analysis. The volume of salvaged tissue was determined as the difference between the initial MTT and follow-up CT lesion volumes and was compared between intravenous rtPA-treated patients and controls.ResultsNo significant difference between the groups was observed in lesion volume assessed from the CTP maps (P > .08). Coefficients of determination for MTT, CBF, and CBV versus follow-up CT lesion volumes were 0.3, 0.3, 0.47, with intravenous rtPA; and 0.53, 0.55, and 0.81 without intravenous rtPA. Regression of MTT on CBF lesion volumes showed codependence (R(2) = 0.98, P < .0001). Mean salvaged tissue volumes with intravenous rtPA were 21.8 +/- 17.1 and 13.2 +/- 13.5 mL in controls; these were significantly different by using nonparametric (P < .03) and Fisher exact tests (P < .04).ConclusionsWithin 3 hours of stroke onset, CBV lesion volume does not necessarily represent dead tissue. MTT lesion volume alone can be used to identify the upper limit of the size of abnormally perfused brain. More brain is salvaged in patients with intravenous rtPA than in controls.

Project description:Background:Stroke is a leading cause of disability and the fifth leading cause of death in the USA. Intravenous alteplase is a highly effective clot-dissolving stroke treatment that must be given in a hospital setting within a time-sensitive window. To increase the use of intravenous alteplase in stroke patients, many US counties enacted policies mandating emergency medical service (EMS) paramedics to bypass local emergency departments and instead directly transport patients to specially equipped stroke centers. The objective of this mixed-methods study is to evaluate the effectiveness of policy enactment as an implementation strategy, how differences in policy structures and processes impact effectiveness, and to explore how the county, hospital, and policy factors explain variation in implementation and clinical outcomes. This paper provides a detailed description of an Agency for Healthcare Quality and Research (AHRQ)-funded protocol, including the use of the Consolidated Framework for Implementation Research (CFIR) in the qualitative design. Methods/design:We will construct the largest-ever national stroke database of Medicare enrollees (~ 1.5 million stroke patients) representing 896 policy counties paired with 1792 non-policy counties, then integrate patient-, hospital-, county-, and state-level covariates from eight different data sources. We will use a difference-in-differences analysis to estimate the overall effect of the policy enactment on intravenous alteplase use (implementation outcome) as well as key patient outcomes. We will also quantitatively examine if variation in the context (urban/rural status) and variation in policy features affect outcomes. Finally, a CFIR-informed multiple case study design will be used to interview informants in 72 stakeholders in 24 counties to identify and validate factors that enable policy effects. Discussion:Policies can be potent implementation strategies. However, the effects of EMS bypass policies to increase intravenous alteplase use have not been rigorously evaluated. By learning how context and policy structures impact alteplase implementation, as well as the barriers and facilitators experienced by stakeholders responsible for policy enactment, the results of this study will inform decisions regarding if and how EMS bypass policies should spread to non-policy counties, and if indicated, creation of a "best practices" toolkit.

Dataset Information

Safety of intravenous alteplase within 4.5 hours for patients awakening with stroke symptoms.

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Safety of intravenous alteplase within 4.5 hours for patients awakening with stroke symptoms.

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