Dataset Information

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

ACCESS DATA

Publications

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

Similar Datasets

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:BackgroundThe optimal dose of tenecteplase vs. alteplase for acute ischemic stroke (AIS) has yet to be established. Therefore, we included the latest randomized controlled trials (RCT) to assess the efficacy and safety of different doses of tenecteplase vs. alteplase for AIS within 4.5 hours of symptom onset.MethodsLiterature was searched in PubMed, Cochrane Library, Embase, Web of Science, and clinical trial registries until February 12, 2023. Odds ratios (OR) with 95% credible intervals (CrI) were estimated using Bayesian network meta-analysis (NMA). Treatments were ranked based on efficacy and safety using the surface under the cumulative ranking curve (SUCRA).ResultsEleven RCTs with 5,475 patients were included. Tenecteplase 0.25 mg/kg and alteplase 0.9 mg/kg had significantly higher rates of excellent functional outcome (tenecteplase: OR, 1.85; 95% CrI, 1.44-2.37; alteplase: OR, 1.60; 95% CrI, 1.29-1.97) and good functional outcome (tenecteplase: OR, 1.54; 95% CrI, 1.19-1.98; alteplase: OR, 1.40; 95% CrI, 1.14-1.74) than placebo, despite an increased risk of symptomatic intracranial hemorrhage. Furthermore, the NMA (OR, 1.16; 95% CrI, 1.01-1.33) and the pairwise meta-analysis (OR, 1.16; 95% CI, 1.02-1.33; P = 0.03) indicated that tenecteplase 0.25 mg/kg was superior to alteplase 0.9 mg/kg in excellent functional outcome. Alteplase 0.9 mg/kg (OR, 2.54; 95% CrI, 1.45-8.08) significantly increased the risk of any intracranial hemorrhage compared with placebo. SUCRA results demonstrated that tenecteplase 0.25 mg/kg ranked first and tenecteplase 0.4 mg/kg ranked last in efficacy outcomes.ConclusionsThe NMA indicated that tenecteplase 0.25 mg/kg and alteplase 0.9 mg/kg are safe and significantly improve clinical outcomes in patients with AIS within 4.5 h of symptom onset. Furthermore, tenecteplase 0.25 mg/kg provides more benefit and has the potential to replace alteplase 0.9 mg/kg in AIS treatment.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/index.php, identifier: CRD42022343948.

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 purposePrompt thrombolytic therapy with intravenous alteplase reduces disability after acute ischemic stroke. In an exploratory analysis, we examined whether long-term survival varied by baseline characteristics after alteplase.MethodsIn this open-treatment, international, randomized, controlled trial, ischemic stroke patients were randomly allocated <6 hours of onset to intravenous alteplase (0.9 mg/kg) plus standard care (n=1515) or standard care alone (n=1520). We followed patients to death, censoring when last known to be alive. We grouped patients by delay to randomization, and good or poor predicted prognosis (calculated from baseline National Institutes of Health Stroke Scale [NIHSS] score and age). We present absolute mortality differences between treated and control groups at 7 days, 6 months, and 18 months poststroke.ResultsAlteplase was not associated with a significant increase in mortality within 18 months (0.6% [95% confidence interval (CI), -2.9% to +4.2] P=0.72] in all patients with complete vital status (99.9%, 3034/3035). In patients randomized <3 hours of stroke, 18-month mortality was lower in the alteplase-treated group than the control group (40.6% [95% CI, 42.6-52.7] versus 47.8% [95% CI, 35.5-45.3]; P=0.0434]. The difference in 18-month mortality between alteplase-treated and control patients was greater in patients who were randomized early (<3 hours) compared with late (3-6 hours; +9% [95% CI, 1-17]; P=0.0317). Alteplase led to a greater improvement in 18-month survival in patients with a poor prognosis than in patients with a good prognosis (+8% [95% CI, 2-14]; P=0.0091).ConclusionsThese exploratory analyses of the third International Stroke Trial (IST-3) trial support improving acute stroke patients' access to earlier alteplase treatment, treatment of patients with poor prognosis, and further randomized controlled trials in minor stroke to replicate these findings.Clinical trial registration urlhttp://www.controlled-trials.com. Unique identifier: ISRCTN25765518.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets