Time to treatment with intravenous alteplase and outcome. Redefining the endpoints of a randomized controlled trial should be viewed with suspicion. This licence only allows you to download this work and share it with others as long as you credit the authors, but you cant change the article in any way or use it commercially. Extend is an investigator driven, phase 3, randomized, multicenter, doubleblind, placebocontrolled study. Sep 21, 2010 although a previous metaanalysis of controlled trials of tissue plasminogen activator for ischemic stroke suggested the possibility of improved outcomes at. The publication of the european cooperative acute stroke study ecass iii. Intravenous thrombolysis for acute ischemic stroke stroke.
The phase iii trial would be designed to examine the effect of the erat on cancer stage at diagnosis, surgical treatment and survival. Openurl1crossref2pubmed 3 web of science4 thrombolysis for acute ischaemic stroke is an effective treatment that has been extremely difficult to implement. The key first step in stroke care is early identification of patients with stroke and triage to centers capable of delivering. Ecass iii represents the most important advance in the acute stroke therapy arena since the publication of the national institute of neurological diseases and stroke tpa trial in 1995 that confirmed the benefits of iv in the ecass iii will likely lead to swift regulatory approval of an extension of the iv. Symptomatic intracranial hemorrhage following intravenous. Active suspension is a type of automotive suspension that controls the vertical movement of the wheels relative to the chassis or vehicle body with an onboard system, rather than in passive suspension where the movement is being determined entirely by the road surface. The original version of the paper reported that there was no baseline difference between the groups. European cooperative acute stroke study iii stroke. Ecass iii underestimates bleeding in the real world. Background intravenous thrombolysis with alteplase is the only approved treatment for acute ischemic stroke, but its efficacy and safety when administered more than 3 hours after the onset of sympt.
Adobe acrobat reader dc download free pdf viewer for. Phase ii exploratory randomised controlled t rial comparing use of electronic clinical decision support ecds for sus pected. Classification of bleeding events according to european cooperative acute stroke study ecass iii and heidelberg bleeding classification hbc. Neurologyresearchinternational late presentation to er unclear time of onset delayed referral from er to neurologist patient or family declining ivtpa absence of ivtpa or delay in ivtpa preparation delay in obtaining brain ct impaired coagulation, due to disease, drugs, etc.
Citation bias favoring positive clinical trials of thrombolytics for acute. The ecass iii results and the tpa paradox the ecass iii results and the tpa paradox davis, stephen. Thrombolytic therapy with recombinant tissue plasminogen activator rtpa is an effective and approved therapy for acute ischemic stroke within 4. The publication of the european cooperative acute stroke study ecass iii expanded the treatment time to thrombolysis for acute ischemic. The ecass family will begin to replace the mainframe cass family starting in late 2017. However, unlike the ecass ii trial, the atlantis study did not find a benefit on the outcome of achieving a modified rankin scale score of 0, 1, or 2 in our post hoc testing. Resultsafter the publication of the ecass iii results in the third quarter of 2008, thrombolysis in the 3 to 4. A recent breakthrough regarding the time window for iv rtpa use was reported by the european cooperative acute stroke study ecass iii, which found that iv rtpa was beneficial to selected patients up to 4. Alteplase n409 and placebo n391 were randomly assigned with stratification for time since symptom onset 0 3 h or 3 6 h. First, make sure that a clients demographic information is complete. Comparison of therapeutic effect of recombinant tissue. Recently a stroke trial called the ecass study was set up.
The ecass family will field in four configurations. The completion of ecass iii and this pooled analysis of all randomised trial data for alteplase provides us with the opportunity to reset. Original article from the new england journal of medicine thrombolysis with alteplase 3 to 4. Analysis of the ninds tpa studies following ecass iii patient. On the other hand, the ecass iii trial reported the incidence of sich using the different definitions adopted by the. In the european cooperative acute stroke study iii ecass iii, alteplase administered 3 045 h after the onset of stroke symptoms resulted in a significant benefit in the primary endpoint modified rankin scale mrs score 01 versus placebo, with no difference in mortality between the treatment groups.
Download citation on apr 1, 2003, m kaste and others published ecass iii. Ecass iii initially was created as a randomized, placebocontrolled, phase 3 trial testing the efficacy and safety of rtpa administered 3 to 4 h after symptom onset. In 2005, based on results from the pooled analysis and slow recruitment, the study protocol was changed to allow an expanded time window from 3 to 4. Although a previous metaanalysis of controlled trials of tissue plasminogen activator for ischemic stroke suggested the possibility of improved outcomes at. Computed tomography was used to exclude patients with signs of major infarction. In the european cooperative acute stroke study iii ecass iii, alteplase administered 3045 h after the onset of stroke symptoms resulted in a significant benefit in the primary endpoint modified rankin scale mrs score 01 versus placebo, with no difference in mortality between the treatment groups. Mar 17, 2015 ecass iii is the only trial to have reported benefit from use of alteplase in the 34.
Riksstroke collaboration background and purposethe european cooperative acute stroke study ecass iii trial and safe implementation of thrombolysis in strokeinternational stroke thrombolysis register sitsistr data were published in 2008. In addition, the rate of spontaneous symptomatic ich in the placebo group of the ecass ii trial, 3. Similarly, if the primary endpoint in ecass iii is recategorized from a modified rankin scale mrs 01 vs 26 to a more realistic mrs 02 vs 36, the supposed benefits of tpa disappears. Download pdfc compare pdf files and identify differences in text, lines, boxes, margins or images with the help of this streamlined and useful application. Most guidelines 1,2 already recommended treatment up to 4. If the safety of treatment is affected by experience and training, as ecass i and ecass ii suggest. In ecass iii, the unadjusted global or for the stroke onset to. Ecassii did not quote a p value for differences in sich. If the uncertainty principle is used to recruit patients for a future trial, then there is a risk that specialist centres will only randomise patients presenting later than 6 h, whereas inexperienced centres may recruit patients much earlier. Time to treatment with intravenous alteplase and outcome in stroke.
Treatment update american college of physicians northern california chapter scientific meeting october 21, 2017 kwan ng md, phd. Although the authors claim that their reevaluation changes ecass from a negative to a positive trial, only two of the three new endpoints were statistically significant and there were more deaths in the tpa group. Publications home of jama and the specialty journals of the. Tissue plasminogen activator for acute ischemic stroke. Treatment of patients with stroke has changed substantially during the past 25 years. Although ecass iii studied rtpa treatment for patients with ais 3 to 4. Identification of lacunar infarcts before thrombolysis in. Stroke treatment with alteplase given 3045 h after onset. The true excitement of ecass iii is that we can hopefully extend the benefit of iv tpa for acute ischemic stroke to a larger cohort of patients. Now hacke et al, reporting for the ecass iii trial, provides randomized data to support the use of tpa in the 3 4. Other factors several other factors have been associated with a. Ecass 1, 1995 ay bl and mrs ecass 2, 1998 oday mrs atlantis part a, 2000 n 142, 30day nihss, infarct vol atlanti ecass ill, 2008 n 821, goday mrs 01 4 hrs 3 hrs time from onset 1 hr 5 hrs ninos group. On the estimation of the sample size for the ecass study.
Reported ichs were categorized according to ecass iii and hbc classifications. Evolution of the thrombolytic treatment window for acute. Approximately 2% to 5% of patients with ais receive rtpa. Nov 01, 2008 to paraphrase the ecass authors and the great yogi berra, having more time does not mean we have more time. In 1995, the ninds rtpa trial showed among selected patients with acute ischemic stroke who were treated with intravenous alteplase within 3 hours of known stroke onset or last known well time had reduced.
Ecass ii, proact intraarterial prourokinase for acute ischemic stroke ii. Ecass iii data in reality prove to have a negative conclusion for iv. Ecass iii confirmed the treatment efficacy up to 4. A total of 101 hemorrhages could be classified with ecass. At the bottom of this guide, you will find the download links for the eclass records. The european cooperative acute stroke study ecass 1 marks an important milestone along the road toward an effective therapy for acute ischemic stroke. So called active suspensions are actually divided into two classes. Blankensteijn, md, phd, section editor thrombolysis for acute ischemic stroke karim hajjar, md, daniel m. Anticipating that patients with large ischemic lesions exceeding onethird of the middle cerebral artery mca territory and detected on ct scans within 6 hours of stroke onset will not benefit from thrombolysis, we trained each participant of the second european cooperative acute stroke study ecass ii in the recognition of early ischemic lesions. The 2008 european cooperative acute stroke study iii ecass iii demonstrated a benefit of intravenous alteplase beyond the conventional 3 hour time window established in the ninds trial 1995, effectively extending the window for alteplase to 4. After those with evidence of brain hemorrhage or major infarction on computed tomography scan were excluded, patients were randomly assigned to receive treatment with intravenous tpa in the approved.
Sich was defined by criteria from the european cooperative acute stroke study ecass ii 46. Stroke is the leading cause of long term disability in developed countries and one of the top causes of mortality worldwide. Feb 01, 2009 the ecass iii results and the tpa paradox the ecass iii results and the tpa paradox davis, stephen. But first, you must read this guide to show you how to use the eclass records. Evaluating a computer aid for assessing stomach symptoms. Intravenous stroke thrombolysis program using telemedicine. Riksstroke collaboration background and purposethe european.
Jul 24, 2015 we aimed to compare the therapeutic effect of recombinant tissue plasminogen activator rtpa administered at different time windows within the first 6 hours after onset of acute ischemic stroke. The median time for the administration of alteplase was 3 hours 59 minutes. Sep 24, 2008 the european cooperative acute stroke study ecass iii was a manufacturersponsored and administered, doubleblind, placebocontrolled trial of the efficacy of alteplase in patients with acute stroke symptoms persisting for 3. Ecass iii is the second randomized trial after the ninds trial of 1995 1 to show a significant treatment effect with intravenous alteplase in the unadjusted analysis of the primary end point. Ecass iii represents the most important advance in the acute stroke therapy arena since the publication of the national institute of neurological diseases and stroke tpa trial in 1995 that confirmed the benefits of iv in the 3 hour time window. European cooperative acute stroke study ecass and ecass ii, investigated a time window of up to 6 hours but failed to show the efficacy of throm bolytic treatment, as defined by each trial.
The primary outcome of the study is the patients status at month 3 assessed by the barthel index 5. Download free adobe acrobat reader dc software for your windows, mac os and android devices to view, print, and comment on pdf documents. The 2008 european cooperative acute stroke study iii ecass iii demonstrated a benefit of intravenous alteplase beyond the conventional 3hour time window established in the ninds trial 1995, effectively extending the window for alteplase to 4. To determine whether clinical presentation or early ct findings of patients enrolled in the first european cooperative acute stroke study ecass i trial would identify lacunar infarcts before. As with the rtcass family the ecass is designed to afford easy migration of the legacy cass tsps to the newer generation ecass tester. European cooperative acute stroke study ecass and ecass ii, investigated a time window of up to 6 hours but failed to show the efficacy of thrombolytic treatment, as defined by each trial. Both analyses used the 3 month mrs as main primary outcome. Published in 2008, the european cooperative acute stroke study ecass iii trial data supported the use of thrombolytic therapy between 3 and 4. Classification of bleeding events stroke aha journals. Publications home of jama and the specialty journals of. It is a doubleblind, randomized, parallel study designed to compare the effect of alteplase and placebo on patients with acute ischemic stroke. The ecass iii results and the tpa paradox deepdyve.
Pdf intravenous thrombolysis with alteplase is the only approved treatment for. Openurl1crossref2pubmed3web of science4 thrombolysis for acute ischaemic stroke is an. Download fulltext pdf thrombolysis with alteplase 3 to 4. Ecass iii was a carefully controlled trial that has results that are rarely replicated in the real world. This report describes a health economic modelling feasibility study undertaken as part of the trial. The ecass iii results and the tpa paradox request pdf. We sought to study the effect of applying the ecass iii selection criteria to the. The fragility of stroke thrombolysis tasman medical journal.
Ecass 3 was a randomized trial comparing tpa treatment vs placebo in 821 patients with stroke who presented 3 to 4. Intravenous alteplase for mild nondisabling acute ischemic. Time to treatment with intravenous alteplase and outcome in. Odds of favourable 3month outcome following ischaemic stroke. Case 3 got tpa, remained stable with nihss 2 mri showed small insular stroke and mra showed. Thrombolysis for acute ischemic stroke sciencedirect.
Riksstroke collaboration background and purposethe. Dawn study main results dwi or ctp assessment with clinical mismatch in the triage of wakeup and late presenting strokes. Efficacy and safety of low dose alteplase for intravenous. Iv tpa up to 3 hours ninds iv tpa 1995 iv tpa up to 4. This nonangiographic, randomised, doubleblind, trial enrolled 800 patients in europe, australia, and new zealand. Lees, md, frcp, glasgow, united kingdom thrombolysis with intravenous alteplase is the primary therapy for acute ischemic stroke, and is approved in most. The identification of lacunar infarcts before thrombolysis would make it possible either to exclude them from treatment or to show that they also may benefit from it. For gastrooesophageal cancers, the alarm symptoms of dysphagia and weight loss are reported by only 32 and 8 % of patients, respectively, and their presence correlates with advancedstage disease. Understand how to download completed ndtrs forms from ecass. I repeated this chisquared comparison for history of. Odds of favourable 3month outcome following ischaemic. For most cancers, only a minority of patients have symptoms meeting the national institute for health and clinical excellence guidance for urgent referral. The past decade has seen substantial advances in the diagnostic and treatment options available to minimize the impact of acute ischemic stroke. The new england journal medicine university of rochester.
Case 3 got tpa, remained stable with nihss 2 mri showed small insular stroke and mra showed resolution occlusion. The european cooperative acute stroke study ecass iii was a manufacturersponsored and administered, doubleblind, placebocontrolled trial of the efficacy of alteplase in patients with acute stroke symptoms persisting for 3. The primary outcome was disability at 3 months, and ecass iii found a greater proportion. Stroke treatment with alteplase given 3045 h after. Originally, the authors described no significant difference in baseline characteristics between the thrombolytic study group and the placebo group. The analysis population consisted of 2775 patients who were included in the previous pooled analysis 8 plus one patient from the ninds trial part 1 1 for whom ott was finally clarified, 794 patients from ecass iii after exclusion of 27 patients in whom exact ott was uncertain and one patient with ott 360 min, plus 100 patients from epithet 7 after. Iv thrombolysis with rtpa and endovascular thrombectomy with stentriever. We aimed to compare the therapeutic effect of recombinant tissue plasminogen activator rtpa administered at different time windows within the first 6. Wellconceived and performed, ecass is the first large, randomized, blinded study of highdose intravenous recombinant tissue plasminogen activator rtpa designed to determine if this thrombolytic therapy is efficacious and. In case of discrepancy, consensus was reached with additional. Ecass iii excluded all patients on blood thinners regardless of inr and all patients over 80 who do worse with ich.
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