scholarly journals Thrombolysis with alteplase 3–4.5 hours after acute ischaemic stroke: trial reanalysis adjusted for baseline imbalances

2020 ◽  
Vol 25 (5) ◽  
pp. 168-171 ◽  
Author(s):  
Brian Scott Alper ◽  
Gary Foster ◽  
Lehana Thabane ◽  
Alex Rae-Grant ◽  
Meghan Malone-Moses ◽  
...  
Keyword(s):  
Ischaemic Stroke ◽  
Acute Ischaemic Stroke ◽  
Intracranial Haemorrhage ◽  
Trial Data ◽  
Stroke Onset ◽  
Primary Efficacy ◽  
Nihss Score ◽  
Primary Efficacy Outcome ◽  
Efficacy Outcome ◽  
Free Status

ObjectivesAlteplase 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.DesignReanalysis 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.SettingEmergency care.Participants821 adults with acute ischaemic stroke who could be treated 3–4.5 hours after symptom onset.InterventionsIntravenous alteplase (0.9 mg/kg of body weight) or placebo.Main outcome measuresThe 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.ResultsWe 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.ConclusionsReanalysis 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 numberNCT00153036.

scholarly journals Mechanical thrombectomy in acute ischaemic stroke patients with pre-interventional intracranial haemorrhage following intravenous thrombolysis

2021 ◽  
pp. 197140092110091
Author(s):  
Hanna Styczen ◽  
Matthias Gawlitza ◽  
Nuran Abdullayev ◽  
Alex Brehm ◽  
Carmen Serna-Candel ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Ischaemic Stroke ◽  
Acute Ischaemic Stroke ◽  
Intracranial Haemorrhage ◽  
Mechanical Thrombectomy ◽  
Intravenous Thrombolysis ◽  
Modified Rankin Scale ◽  
Large Vessel Occlusion ◽  
Stroke Patients ◽  
Vessel Occlusion

Background Data on outcome of endovascular treatment in patients with acute ischaemic stroke due to large vessel occlusion suffering from intravenous thrombolysis-associated intracranial haemorrhage prior to mechanical thrombectomy remain scarce. Addressing this subject, we report our multicentre experience. Methods A retrospective analysis of consecutive acute ischaemic stroke patients treated with mechanical thrombectomy due to large vessel occlusion despite the pre-interventional occurrence of intravenous thrombolysis-associated intracranial haemorrhage was performed at five tertiary care centres between January 2010–September 2020. Baseline demographics, aetiology of stroke and intracranial haemorrhage, angiographic outcome assessed by the Thrombolysis in Cerebral Infarction score and clinical outcome evaluated by the modified Rankin Scale at 90 days were recorded. Results In total, six patients were included in the study. Five individuals demonstrated cerebral intraparenchymal haemorrhage on pre-interventional imaging; in one patient additional subdural haematoma was observed and one patient suffered from isolated subarachnoid haemorrhage. All patients except one were treated by the ‘drip-and-ship’ paradigm. Successful reperfusion was achieved in 4/6 (67%) individuals. In 5/6 (83%) patients, the pre-interventional intracranial haemorrhage had aggravated in post-interventional computed tomography with space-occupying effect. Overall, five patients had died during the hospital stay. The clinical outcome of the survivor was modified Rankin Scale=4 at 90 days follow-up. Conclusion Mechanical thrombectomy in patients with intravenous thrombolysis-associated intracranial haemorrhage is technically feasible. The clinical outcome of this subgroup of stroke patients, however, appears to be devastating with high mortality and only carefully selected patients might benefit from endovascular treatment.

scholarly journals S246. THE EFFECT OF INCORRECT SCALE ADMINISTRATION ON DATA QUALITY IN SCHIZOPHRENIA CLINICAL TRIALS

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S132-S132
Author(s):  
Alan Kott ◽  
David Daniel
Keyword(s):  
Clinical Trials ◽  
Clinical Global Impression ◽  
Primary Outcome Measure ◽  
Primary Efficacy ◽  
Double Blind ◽  
Clinical Global Impression Scale ◽  
Primary Efficacy Outcome ◽  
Pooled Data ◽  
Efficacy Outcome ◽  
Time Stamps

Abstract Background The availability of date and time stamps of interview start times on eCOA systems permits monitoring and documentation of the order of administration of scales and instruments at each visit. The Clinical Global Impression Scale (CGI) is a holistic instrument that synthesizes all information available from the subject, caregivers, medical notes, etc. and is therefore typically required to be rated last at a particular visit. In the current retrospective analysis of double blind eCOA collected schizophrenia data pooled from multiple clinical trials we assessed the percent of visits where CGI was not administered last among other efficacy assessments. Additionally we assessed whether the inappropriate administration order of Clinical Global Impression Scale was associated with discrepancies in the data and change from baseline between the CGI and the primary efficacy outcome. Methods Available eCOA data were pooled from schizophrenia double blind, placebo controlled clinical trials. Within the data, we identified those visits where the CGI was not administered last among other efficacy assessments (inappropriate administration order). Within each trial we identified as discordant those data where the actual primary efficacy score or its change from baseline differed by at least two standard deviations from the expected score after linear regression. For this procedure the CGI- S score used as a predictor and the primary efficacy outcome as dependent variable. Logistic regression was then used on pooled data to explore whether the incorrect order of CGI administration increased the odds of discordant ratings between the CGI and primary outcome measure. Results The dataset consisted of 5,784 paired ratings of the CGI and the primary efficacy outcome. Among these, a total of 4,628 visits allowed to calculate change from baseline. Inappropriate order of CGI administration was identified in a total of 443 visits (7.7% of all visits). Discrepancies between CGI-S and the primary efficacy outcome were identified in 292 visits (5.1% of data) and discrepancies between change from baseline in CGI-S and in the primary efficacy outcome were observed in 249 cases (5.3% of data). The presence of incorrectly administered CGI increased the odds of raw score discrepancy 1.6x (95%CI 1.1–2.4), and the odds of discrepancy in change from baseline 1.8x (95%CI 1.2–2.7), both significant with p <0.01. Discussion Our data indicate a relatively large percent of visits suffer from an incorrect scale administration order. We have previously explored a number of sources of possible noise in schizophrenia clinical trials. Current analyses identified a significant effect of incorrect scale administration on the presence of between scale discordances. Such findings indicate that order of CGI administration should be mandated in schizophrenia clinical trials and enforced by eCOA platforms. Additionally, violations to correct scale administration should be monitored through analytic programs and acted upon in case of repeated occurrences at the rater or site level.

Efficacy and Safety of Edoxaban Versus Enoxaparin for the Prevention of Venous Thromboembolism Following Total Hip Arthroplasty: STARS J-V trial

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3320-3320 ◽  
Author(s):  
Takeshi Fuji ◽  
Satoru Fujita ◽  
Shintaro Tachibana ◽  
Yohko Kawai ◽  
Yukihiro Koretsune ◽  
...  
Keyword(s):  
Total Hip Arthroplasty ◽  
Major Bleeding ◽  
Thromboembolic Events ◽  
Primary Efficacy ◽  
Efficacy And Safety ◽  
Bleeding Events ◽  
Primary Efficacy Outcome ◽  
Treatment Groups ◽  
Efficacy Outcome ◽  
Lead Investigator

Abstract Abstract 3320 Introduction: Edoxaban is an oral, direct factor Xa inhibitor in clinical development for the prevention and treatment of thromboembolic events. The aim of this non-inferiority trial was to determine the efficacy and safety of edoxaban compared with enoxaparin sodium (enoxaparin) after total hip arthroplasty (THA) in Japan. Methods: This was a randomized, double-blind, double-dummy, enoxaparin-controlled, multicenter trial. Patients were randomized to oral edoxaban 30 mg once daily (QD) or subcutaneous enoxaparin 2,000 IU, equivalent to 20 mg, twice daily (BID) for 11 to 14 days. Edoxaban was initiated 6–24 hours after surgery and enoxaparin was initiated 24–36 hours after surgery which is the Japanese standard of care. The primary efficacy outcome was the composite of symptomatic and asymptomatic deep vein thrombosis (DVT), and pulmonary embolism (PE). The primary safety outcome was the incidence of major and clinically relevant non-major bleeding. Results: A total of 610 patients were randomized. There were no clinically relevant differences in baseline characteristics between the treatment groups. The mean age was 62.8 years and mean body weight was 57.4 kg (Efficacy analysis set). The primary efficacy outcome occurred in 6 of 255 (2.4%) patients receiving edoxaban and 17 of 248 (6.9%) patients receiving enoxaparin (relative risk reduction=65.7%; absolute risk difference -4.5%, 95% CI, -8.6% to -0.9%; P<0.001 for non-inferiority; P=0.0157 for superiority). The thromboembolic events were all asymptomatic DVT (Table). No symptomatic DVT or PE was observed in both treatment groups. The incidence of major and clinically relevant non-major bleeding events was 2.6% (8/303) vs 3.7% (11/301) in the edoxaban and enoxaparin groups, respectively (P=0.475). Major bleeding occurred in 0.7% of the edoxaban group and 2.0% of the enoxaparin group. The rates of elevated serum aminotransferase levels of more than 3 times the upper limit of normal was 2.6% with edoxaban versus 10% with enoxaparin. Conclusions: The STARS J-V trial demonstrated that oral edoxaban 30 mg QD has efficacy superior to enoxaparin 2,000 IU BID in the prevention of thromboembolic events following THA and is associated with a similar incidence of major and clinically relevant non-major bleeding events. Disclosures: Fuji: Astellas: Consultancy; Showa Ikakogyo: Consultancy; Daiichi Sankyo: Consultancy; Bayer: Consultancy. Fujita:Daiichi Sankyo: Consultancy; Astellas: Consultancy; GlaxoSmithkline: Consultancy. Tachibana:Daiichi Sankyo: Consultancy. Kawai:Daiichi Sankyo: Consultancy; Toyama Chemical: Consultancy. Koretsune:Daiichi Sankyo: Consultancy, National Lead Investigator. Yamashita:Daiichi Sankyo: Consultancy, National Lead Investigator; Otsuka Pharmaceutical: Paid instructor; Sanofi-aventis: Paid instructor; Teijin Pharma: Paid instructor. Nakamura:Daiichi Sankyo: Consultancy; GlaxoSmithkline: Consultancy; Astellas: Consultancy.

scholarly journals Dabigatran Etexilate or Warfarin in the Treatment of Acute Venous Thromboembolism in Western European Patients: A Pooled Analysis of RE-COVER® and RE-COVER II™

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4730-4730
Author(s):  
Sebastian Schellong ◽  
Henry Eriksson ◽  
Samuel Z. Goldhaber ◽  
Martin Feuring ◽  
Stefan Hantel ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Research Funding ◽  
Dabigatran Etexilate ◽  
Primary Efficacy ◽  
Bleeding Events ◽  
Primary Efficacy Outcome ◽  
Efficacy Outcome ◽  
Safety Outcomes ◽  
Western European ◽  
Acute Venous Thromboembolism

Abstract Introduction: In the RE-COVER®/RE-COVER II™ global randomized trials investigating the treatment of acute venous thromboembolism (VTE), efficacy and safety outcomes of dabigatran etexilate (dabigatran) versus warfarin were compared. This sub-analysis of pooled RE-COVER®/RE-COVER II™ data compares the safety and efficacy of dabigatran versus warfarin in the Western European sub-population. Methods: In the RE-COVER®/RE-COVER II™ trials, patients with acute VTE, initially receiving parenteral anticoagulation, were randomized to warfarin (INR 2-3) or dabigatran (150 mg twice daily) for 6 months and followed up for 30 days. The primary efficacy outcome was recurrent, symptomatic VTE/VTE-related death. Safety outcomes were major bleeding events (MBEs), a composite of MBEs or clinically relevant non-major bleeding events (MBEs/CRBEs) and any bleeding during the 6-month, oral-only treatment period. All outcomes were centrally adjudicated. Data from the Western European sub-population were analyzed using a Cox regression model with factor treatment stratified by study, assuming different baseline hazards per study. Results: This sub-analysis included 1239 patients for the efficacy analysis (dabigatran n = 613; warfarin n = 626) and 1192 patients for safety (dabigatran n = 588; warfarin n = 604) from all 13 Western European countries participating in the RE-COVER®/RE-COVER II™ trials. For the primary efficacy outcome, the rate of VTE/VTE-related death in patients receiving dabigatran was 2.1% (n = 13) compared with 2.9% (n = 18) in those receiving warfarin. However, this difference did not reach statistical significance (hazard ratio [HR] 0.74; 95% confidence interval [CI], 0.36-1.5). Of the safety outcomes, rates of MBEs were similar between both treatment groups (1.4% for dabigatran [n = 8] and 1.3% for warfarin [n = 8]; HR 1.02; 95% CI, 0.38-2.71). Rates of MBEs/CRBEs were significantly lower in patients receiving dabigatran than in those receiving warfarin at 5.1% (n = 30) and 9.4% (n = 57), respectively (HR 0.52; 95% CI, 0.34-0.82). Any bleeding events were also statistically lower in the dabigatran group (17.5%; n = 103) compared with warfarin (23.8%; n = 144) (HR 0.7; 95% CI, 0.54-0.90). Conclusions: In this Western European sub-analysis of pooled data from the RE-COVER®/ RE-COVER II™ trials, dabigatran was as effective as warfarin in the treatment of acute VTE. There was a significant reduction in MBE/CRBE and in any bleeding events in the dabigatran treatment group. Disclosures Schellong: Boehringer Ingelheim: Consultancy. Eriksson:Boehringer Ingelheim: Consultancy. Goldhaber:Boehringer Ingelheim: Consultancy, Research Funding. Feuring:Boehringer Ingelheim: Employment. Hantel:Boehringer Ingelheim Pharma GmbH and Co. KG: Employment. Kreuzer:Boehringer Ingelheim Pharma GmbH and Co. KG: Employment. Schulman:Boehringer Ingelheim: Honoraria, Research Funding; Bayer: Honoraria; Baxter: Honoraria; Octapharma: Research Funding. Kakkar:Boehringer Ingelheim: Consultancy, Honoraria, Research Funding.

scholarly journals Low-Dose Statins Improve Prognosis of Patients with Ischaemic Stroke Undergoing Intra-Arterial Thrombectomy: A Prospective Cohort Study

2021 ◽  
Author(s):  
Chaohua Cui ◽  
Shuju Dong ◽  
Qian Liu ◽  
Jiajia Bao ◽  
Lijie Gao ◽  
...  
Keyword(s):  
Ischaemic Stroke ◽  
Acute Ischaemic Stroke ◽  
Low Dose ◽  
Lower Percentage ◽  
High Dose ◽  
Improvement Rate ◽  
Death Rates ◽  
Nihss Score ◽  
Statin Group ◽  
Statin Use

Abstract Background: High-dose statins are recommended as preventive drugs in guidelines for patients with ischaemic stroke undergoing thrombectomy. Not only in clinical practice but also based on large-scale studies, low-dose statins have been widely used and demonstrated to be efficient in Asian populations. However, it remains unknown whether low-dose statin is related to the prognosis of patients with thrombectomy. Can low-dose statins reduce the risk of bleeding at the same time?Methods: We prospectively collected data from patients with acute ischaemic stroke undergoing intra-arterial thrombectomy. Efficacy outcomes were National Institutes of Health Stroke Scale (NIHSS) score improvement at 7 days after admission and a favourable functional outcome (FFO) at 90 days. Safety outcomes were rates of in-hospital haemorrhage events and death within 2 years. Results: We included 256 patients in this study. Compared with the control group, the low-dose statin group had a higher NIHSS improvement rate at 7 days, a higher FFO rate at 90 days and a lower death rate within 2 years. The low-dose statin group had a lower percentage of gastrointestinal haemorrhage. Statin use was significantly related to an improved NIHSS score (p=0.028, OR=1.773) at 7 days and FFO (P<0.001, OR=2.962) at 90 days and to lower death rates (P=0.025, or=0.554) within 2 years.Conclusion: In Asian acute ischaemic stroke patients with intra-arterial thrombectomy, low-dose statin use was significantly related to NIHSS improvement at 7 days, FFO at 90 days and decreased death rates within 2 years.

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

2020 ◽  
Vol 2 (1) ◽  
pp. e000030 ◽  
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.

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