Developing a multivariable prediction model for functional outcome after reperfusion therapy for acute ischaemic stroke: study protocol for the Targeting Optimal Thrombolysis Outcomes (TOTO) multicentre cohort study

IntroductionIntravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) is the only approved pharmacological reperfusion therapy for acute ischaemic stroke. Despite population benefit, IVT is not equally effective in all patients, nor is it without significant risk. Uncertain treatment outcome prediction complicates patient treatment selection. This study will develop and validate predictive algorithms for IVT response, using clinical, radiological and blood-based biomarker measures. A secondary objective is to develop predictive algorithms for endovascular thrombectomy (EVT), which has been proven as an effective reperfusion therapy since study inception.Methods and analysisThe Targeting Optimal Thrombolysis Outcomes Study is a multicenter prospective cohort study of ischaemic stroke patients treated at participating Australian Stroke Centres with IVT and/or EVT. Patients undergo neuroimaging using multimodal CT or MRI at baseline with repeat neuroimaging 24 hours post-treatment. Baseline and follow-up blood samples are provided for research use. The primary outcome is good functional outcome at 90 days poststroke, defined as a modified Rankin Scale (mRS) Score of 0–2. Secondary outcomes are reperfusion, recanalisation, infarct core growth, change in stroke severity, poor functional outcome, excellent functional outcome and ordinal mRS at 90 days. Primary predictive models will be developed and validated in patients treated only with rt-PA. Models will be built using regression methods and include clinical variables, radiological measures from multimodal neuroimaging and blood-based biomarkers measured by mass spectrometry. Predictive accuracy will be quantified using c-statistics and R2. In secondary analyses, models will be developed in patients treated using EVT, with or without prior IVT, reflecting practice changes since original study design.Ethics and disseminationPatients, or relatives when patients could not consent, provide written informed consent to participate. This study received approval from the Hunter New England Local Health District Human Research Ethics Committee (reference 14/10/15/4.02). Findings will be disseminated via peer-reviewed publications and conference presentations.

Download Full-text

Faculty Opinions recommendation of Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718525168.793499033 ◽

2014 ◽

Author(s):

Eivind Berge

Keyword(s):

Ischaemic Stroke ◽

Acute Ischaemic Stroke ◽

Individual Patient Data ◽

Meta Analysis ◽

Intravenous Thrombolysis ◽

Treatment Delay ◽

Patient Data ◽

Stroke Severity ◽

Randomised Trials ◽

Effect Of Treatment

Download Full-text

Efficacy and safety of butylphthalide for patients who had acute ischaemic stroke receiving intravenous thrombolysis or endovascular treatment (BAST trial): study protocol for a randomised placebo-controlled trial

BMJ Open ◽

10.1136/bmjopen-2020-045559 ◽

2021 ◽

Vol 11 (5) ◽

pp. e045559

Author(s):

Xuelei Zhang ◽

Anxin Wang ◽

Jing Yu Zhang ◽

Baixue Jia ◽

Xiaochuan Huo ◽

...

Keyword(s):

Ischaemic Stroke ◽

Endovascular Treatment ◽

Functional Outcome ◽

Acute Ischaemic Stroke ◽

Controlled Trial ◽

Intravenous Thrombolysis ◽

Serious Adverse Events ◽

Double Blind ◽

Ischaemic Injury ◽

Study Results

IntroductionAs a neuroprotective medication, butylphthalide (NBP) may help protect against cerebral ischaemic injury. However, evidence on whether NBP influences the outcomes of patients who had acute ischaemic stroke who are receiving revascularisation treatment is limited. This study aims to evaluate whether additional NBP therapy can improve the functional outcome of patients who receive intravenous recombinant tissue plasminogen activator and/or endovascular treatment (EVT).Methods and analysisThe study will be a randomised, double-blind, placebo-controlled, multiple-centre, parallel group trial. The sample size is estimated at 1200 patients. Eligible patients will be randomised at a 1:1 ratio to receive either NBP or placebo daily for 90 days, which will include 14 days of injections and 76 days of capsules. The first use of NBP/placebo will be started within 6 hours of onset of ischaemic stroke. The primary outcome is the functional outcome as assessed by the 90-day modified Rankin Scale, adjusted for baseline scores on the National Institutes of Health Stroke Scale. The primary safety outcome is the percentage of serious adverse events during the 90 days of treatment. This trial will determine whether NBP medication benefits patients who had acute ischaemic stroke who receive intravenous thrombolysis or EVT.Ethics and disseminationThe protocol was written according to the general ethical guidelines of the Declaration of Helsinki and approved by the Institutional Review Board/Ethics Committee of Beijing Tiantan Hospital, Capital Medical University with approval number KY 2018-003-02. Ethics committees of all participating sites have approved the study . Results of the study will be published in peer-reviewed scientific journals and shared in scientific presentations.Trial registration numberNCT03539445.

Download Full-text

Endovascular treatment of acute ischaemic stroke in octogenarians and nonagenarians compared with younger patients

The Neuroradiology Journal ◽

10.1177/1971400919840847 ◽

2019 ◽

Vol 32 (4) ◽

pp. 303-308 ◽

Cited By ~ 2

Author(s):

Yasuhiro Kawabata ◽

Norio Nakajima ◽

Hidenori Miyake ◽

Shunichi Fukuda ◽

Tetsuya Tsukahara

Keyword(s):

Ischaemic Stroke ◽

Functional Outcome ◽

Scale Score ◽

Endovascular Therapy ◽

Acute Ischaemic Stroke ◽

Intravenous Thrombolysis ◽

Favourable Outcome ◽

Modified Rankin Scale ◽

Very Elderly ◽

Younger Patients

Purpose: Endovascular therapy for emergent large vessel occlusion has been established as the standard approach for acute ischaemic stroke. However, the effectiveness and safety of endovascular therapy in the very elderly population has not been proved. Objective: To determine the safety and effectiveness of endovascular therapy in octogenarians and nonagenarians. Methods: We retrospectively reviewed all patients who underwent endovascular therapy at two stroke centres between April 2012 and July 2018. Functional outcome was assessed using the modified Rankin scale at 90 days after stroke or at discharge. A favourable outcome was defined as a modified Rankin scale score of 0–2 or not worsening of the modified Rankin scale score before stroke. Outcome was compared between younger patients (aged 46–79 years, n = 40) and octogenarians and nonagenarians (aged 80–97 years, n = 19). Results: Octogenarian and nonagenarian patients had pre-stroke functional deficit (modified Rankin scale score >1) more frequently than younger patients (57.9% vs. 20.0%, respectively, P = 0.0059). No difference was observed between very elderly and younger patients in the rate of successful reperfusion (89.5% vs. 67.5%, respectively, P = 0.11), favourable functional outcome (47.4% vs. 45.0%, respectively, P = 1.00) and mortality (21.1% vs. 27.5%, respectively, P = 1.00). On multiple regression analysis, successful reperfusion, concomitant use of intravenous thrombolysis, and out-of-hospital onset were independent predictors of favourable outcome ( P = 0.0003, 0.015 and 0.028, respectively). Conclusions: Successful reperfusion, concomitant use of intravenous thrombolysis, and out-of-hospital onset were clinical predictors of favourable outcome. However, we did not observe an age-dependent effect of clinical outcome after endovascular therapy.

Download Full-text

Effect of Treatment Delay, Age, and Stroke Severity on the Effects of Intravenous Thrombolysis with Alteplase for Acute Ischaemic Stroke: A Meta-analysis of Individual Patient Data from Randomized Trials

Journal of Emergency Medicine ◽

10.1016/j.jemermed.2015.03.037 ◽

2015 ◽

Vol 48 (5) ◽

pp. 650

Author(s):

Graham Ingalsbe

Keyword(s):

Ischaemic Stroke ◽

Acute Ischaemic Stroke ◽

Randomized Trials ◽

Individual Patient Data ◽

Meta Analysis ◽

Intravenous Thrombolysis ◽

Treatment Delay ◽

Patient Data ◽

Stroke Severity ◽

Effect Of Treatment

Download Full-text

Sedation versus general anaesthesia in endovascular therapy for anterior circulation acute ischaemic stroke: the multicentre randomised controlled AMETIS trial study protocol

BMJ Open ◽

10.1136/bmjopen-2018-027561 ◽

2019 ◽

Vol 9 (9) ◽

pp. e027561 ◽

Cited By ~ 3

Author(s):

Russell Chabanne ◽

Charlotte Fernandez-Canal ◽

Vincent Degos ◽

Anne-Claire Lukaszewicz ◽

Lionel Velly ◽

...

Keyword(s):

Ischaemic Stroke ◽

Functional Outcome ◽

General Anaesthesia ◽

Endovascular Therapy ◽

Acute Ischaemic Stroke ◽

Intravenous Thrombolysis ◽

Functional Independence ◽

Acute Pulmonary Oedema ◽

Anterior Circulation ◽

Randomised Controlled

IntroductionEndovascular thrombectomy is the standard of care for anterior circulation acute ischaemic stroke (AIS) secondary to emergent large vessel occlusion in patients who qualify. General anaesthesia (GA) or conscious sedation (CS) is usually required to ensure patient comfort and avoid agitation and movement during thrombectomy. However, the question of whether the use of GA or CS might influence functional outcome remains debated. Indeed, conflicting results exist between observational studies with better outcomes associated with CS and small monocentric randomised controlled trials favouring GA. Therefore, we aim to evaluate the effect of CS versus GA on functional outcome and periprocedural complications in endovascular mechanical thrombectomy for anterior circulation AIS.Methods and analysisAnesthesia Management in Endovascular Therapy for Ischemic Stroke (AMETIS) trial is an investigator initiated, multicentre, prospective, randomised controlled, two-arm trial. AMETIS trial will randomise 270 patients with anterior circulation AIS in a 1:1 ratio, stratified by centre, National Institutes of Health Stroke Scale (≤15 or >15) and association of intravenous thrombolysis or not to receive either CS or GA. The primary outcome is a composite of functional independence at 3 months and absence of perioperative complication occurring by day 7 after endovascular therapy for anterior circulation AIS. Functional independence is defined as a modified Rankin Scale score of 0–2 by day 90. Perioperative complications are defined as intervention-associated arterial perforation or dissection, pneumonia or myocardial infarction or cardiogenic acute pulmonary oedema or malignant stroke evolution occurring by day 7.Ethics and disseminationThe AMETIS trial was approved by an independent ethics committee. Study began in august 2017. Results will be published in an international peer-reviewed medical journal.Trial registration numberNCT03229148.

Download Full-text

Impact of interhospital transfer on patients undergoing endovascular thrombectomy for acute ischaemic stroke in an Australian setting

BMJ Neurology Open ◽

10.1136/bmjno-2019-000030 ◽

2020 ◽

Vol 2 (1) ◽

pp. e000030 ◽

Cited By ~ 1

Author(s):

Leon Stephen Edwards ◽

Christopher Blair ◽

Dennis Cordato ◽

Alan McDougall ◽

Nathan Manning ◽

...

Keyword(s):

Ischaemic Stroke ◽

Functional Outcome ◽

Outcome Measures ◽

Acute Ischaemic Stroke ◽

Intravenous Thrombolysis ◽

Stroke Onset ◽

Endovascular Thrombectomy ◽

Interhospital Transfer ◽

Significant Difference ◽

The Impact

ObjectiveTo assess the impact of interhospital transfer on the interplay between functional outcome, mortality, reperfusion rates and workflow time metrics in patients undergoing endovascular thrombectomy (EVT) for acute ischaemic stroke due to large vessel occlusion (LVO) in the anterior cerebral circulation.Design, setting and participantsThis is an analysis of a prospective database of consecutive patients undergoing EVT for LVO presenting between January 2017 and December 2018 at a single Australian comprehensive stroke centre (CSC). Patients presented directly or were transferred to the CSC from 21 sites across New South Wales and the Australian Capital Territory.Main outcome measuresThe main outcome measures were rate of good 90-day functional outcome (modified Rankin Scale 0–2), successful reperfusion (Thrombolysis in Cerebral Infarction scale grade 2b or 3), symptomatic intracerebral haemorrhage (sICH) and 90-day mortality. Key workflow time metric milestones were examined.Results154 of 213 (72%) patients were interhospital transfers. There was no significant difference in baseline characteristics including age, National Institutes of Health Stroke Scale score, intravenous thrombolysis administration or procedure time between transferred and direct presenters (all p>0.05). Transferred patients had worse 90-day functional outcome (39.6% vs 61.0%, OR 0.42, 95% CI 0.23 to 0.78), higher mortality (25.3% vs 6.8%, OR 4.66, CI 1.59 to 13.70) and longer stroke onset to treatment (groin puncture) time (298 min vs 205 min, p<0.01). Successful reperfusion rates and sICH were similar between the cohorts (96.8% vs 98.3%, and 7.8% vs 3.4%).ConclusionInterhospital transfer is associated with longer stroke onset to treatment, worse 90-day functional outcome and higher mortality compared with patients presenting directly to the CSC.

Download Full-text

Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials

The Lancet ◽

10.1016/s0140-6736(14)60584-5 ◽

2014 ◽

Vol 384 (9958) ◽

pp. 1929-1935 ◽

Cited By ~ 1020

Author(s):

Jonathan Emberson ◽

Kennedy R Lees ◽

Patrick Lyden ◽

Lisa Blackwell ◽

Gregory Albers ◽

...

Keyword(s):

Ischaemic Stroke ◽

Acute Ischaemic Stroke ◽

Individual Patient Data ◽

Meta Analysis ◽

Intravenous Thrombolysis ◽

Treatment Delay ◽

Patient Data ◽

Stroke Severity ◽

Randomised Trials ◽

Effect Of Treatment

Download Full-text

Prevalence of Atrial Fibrillation in Patients with Acute Ischaemic Stroke: A Multicentric Cohort Study

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2021/49603.15439 ◽

2021 ◽

Author(s):

Indu Bhana ◽

Archana Ojha ◽

Rajendra Kumar Pandey ◽

Durgvijay Singh ◽

Mahendra Chourasiya

Keyword(s):

Atrial Fibrillation ◽

Cohort Study ◽

Ischaemic Stroke ◽

Acute Ischaemic Stroke ◽

Urban Areas ◽

Tertiary Care ◽

Stroke Severity ◽

Stroke Patients ◽

Elderly Age ◽

Female Population

Introduction: India reports high prevalence of stroke, both in rural and urban areas. Secondary prevention is very important in patients with stroke to reduce the morbidity and mortality associated with it. Atrial Fibrillation (AF) is an important risk factor for stroke which can lead to cerebrovascular insult. Aim: To study the prevalence of AF in patients with acute ischaemic stroke and to obtain the association between the parameters such as age, gender, stroke territory and stroke severity by National Institute of Health Stroke Scale (NIHSS). Materials and Methods: In this multicentric cohort study, 150 patients with acute ischaemic stroke (new onset or recurrent) were studied at tertiary care centres located in Indore (Madhya Pradesh), Prayagraj, Moradabad and Lucknow (Uttar Pradesh) from January 2020 to January 2021. Age, gender, stroke territory and stroke severity by NIHSS was recorded and compared between those with and without AF. The Chi-square test was used to assess the association and obtaining significance. Results: Prevalence of AF in patients with stroke was 8% (n=12), which was significantly high in female population (8 out of 12; p=0.025), those with age more than 60 years (10 out of 12; p=0.011), with atrial dilatation (9 out of 12; p=0.124), patients with severe stroke as per NIHSS (7 out of 12; p=0.001) and those with poor outcome (8 out of 12; p=0.012). Conclusion: In the present study, 8% of the stroke patients had AF with stroke. Elderly age, female sex, and large atrial size on Echocardiogram (ECHO) should be intensively investigated for AF in stroke patients.

Download Full-text

Risk Factors for Pneumonia in Patients with Acute Ischaemic Stroke- A Retrospective Study

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2021/47188.14404 ◽

2021 ◽

Author(s):

Roy Thomas

Keyword(s):

Risk Factors ◽

Ischaemic Stroke ◽

Acute Ischaemic Stroke ◽

Test Score ◽

Neurological Complication ◽

Tertiary Care ◽

Significant Risk ◽

Chronic Obstructive ◽

Stroke Severity ◽

Increased Risk

Introduction: The most common non-neurological complication of stroke is infection. Stroke, associated with pneumonia is one among them. A few studies have identified prognostic predictors of pneumonia in stroke. Aim: To identify the risk factors of pneumonia in acute ischaemic stroke patients. Materials and Methods: This retrospective cohort study included medical records of 470 adult patients with acute ischaemic stroke between June 2015 to June 2020 (five years) in a Tertiary Care Medical College and Hospital. Among them, 173 had stroke associated with pneumonia. The clinical parameters-age, gender, lesion location, stroke severity (Glasgow Coma Scale (GCS)) , National Institute of Health Stroke Scale (NIHSS), Modified Barthel Activities of Daily Living (ADL) index, water swallow test, vascular risk factors and co-existing conditions (pre-existent Chronic Obstructive Pulmonary Disease (COPD), atrial fibrillation, renal electrolyte dysfunction, hypoproteinaemia) were compared. Chi-square test and logistic regression analysis were used for statistical analysis. Results: In this study, the following factors were associated with increased risk of developing pneumonia-age >70 years, bed ridden status, GCS ≤13, NIHSS ≥5, water swallow test score ≤2. Among them, multivariate analysis identified bed ridden status and water swallow test as independent predictors. Conclusion: Bed ridden status and water swallow test score were significant risk factors of ischaemic stroke associated with pneumonia. Hence, an early identification of these factors and a better knowledge of them may help in better care and prevention of pneumonia in acute ischaemic stroke.

Download Full-text