Clinical trial NCT00153036: Rt-PA in the Treatment of Acute Ischemic Stroke
Official title: ECASS III - European Cooperative Acute Stroke Study III: A Placebo Controlled Trial of Alteplase (Rt-PA) in Acute Ischemic Hemispheric Stroke Where Thrombolysis is Initiated Between 3 and 4 Hours 30 Minutes After Stroke Onset
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cerebrovascular Accident
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2005-09-12
Enrollment: 821
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: To collect additional confirmatory data on alteplase(rt-PA) in the European setting and to demonstrate that the treatment of patients between 3 and 4.30 hours of onset of symptoms of acute ischemic stroke with rt-PA compared to placebo-treated patients will result in an improved clinical outcome without increase of fatality rate.


Eligibility criteria: Inclusion Criteria:

* Female or male inpatients
* Age: 18 - 80 years.
* Clinical diagnosis of ischemic stroke causing a measurable neurological deficit defined as impairment of language, motor function, cognition and/or gaze, vision or neglect. Ischemic stroke is defined as an event characterized by the sudden onset of an acute focal neurologic deficit presumed to be due to cerebral ischemia after CT scan excludes hemorrhage.
* Onset of symptoms between 3 and 4 hours prior to initiation of administration of study drug.
* Stroke symptoms are to be present for at least 30 minutes and have not significantly improved before treatment. Symptoms must be distinguishable from an episode of generalized ischemia (i.e. syncope), seizure, or migraine disorder.
* Patient is willing to participate voluntarily and to sign a written patient informed consent. Informed consent will be obtained from each patient or the subject's legally authorized representative or relatives, or deferred where applicable, according to the regulatory and legal requirements of the participating country.
* Patients who are unable to sign but who are able to understand the meaning of participation in the study may give an oral witnessed informed consent. These patients have to make clear undoubtfully that they are willing to participate voluntarily and must be able to understand an explanation of the contents of he information sheet.
* Willingness and ability to comply with the protocol.

Exclusion Criteria:

* Evidence of intracranial hemorrhage (ICH) on the CT-scan.
* Symptoms of ischaemic attack began more than 4 hours and 30 minutes prior to infusion start or when time of symptom onset is unknown.
* Minor neurological deficit or symptoms rapidly improving before start of infusion.
* Severe stroke as assessed clinically (e.g. NIHSS\>25) and/or by appropriate imaging techniques.
* Epileptic seizure at onset of stroke
* Symptoms suggestive of subarachnoid haemorrhage, even if the CT-scan is normal.
* Administration of heparin within the previous 48 hours and a thromboplastin time exceeding the upper limit of normal for laboratory
* History of prior stroke and concomitant diabetes. \* Prior stroke within the last 3 months
* Platelet below 100,000/mm3. \* Systolic blood pressure \>185 mmHg or diastolic blood pressure \>110 mmHg, or aggressive management (IV medication) necessary to reduce BP to these limits.
* Blood glucose \<50 or \> 400 mg/dl (\< 2.77 or \> 22.15 mmol / l). \* Known haemorraghic diathesis
* Patients receiving oral anticoagulants. \* Manifest or recent severe or dangerous bleeding
* Known history of or suspected intracranial haemorrhage
* Suspected subarachnoid haemorrhage or condition after subarachnoid haemorrhage from aneurysm
* History of central nervous system damage (i.e. neoplasm, aneurysm, intracranial or spinal surgery)
* Haemorrhagic retinopathy,e.g. in diabetes (vision disturbances may indicate haemorrhagic retinopathy)
* Recent (less than 10 days) traumatic external heart massage, obstetrical delivery, recent puncture of a non-compressible blood-vessel (e.g. subclavian or jugular vein puncture.
* bacterial endocarditis, pericarditis.\* Acute pancreatitis
* Documented ulcerative gastrointestinal disease during the last 3 months, oesophageal varices, arterial- aneurysm, arterial/venous malformation
* Neoplasm with increased bleeding risk

Primary outcomes:
measure: modified Rankin scale (mRS) 0-1 (favourable outcome) at Day 90
timeFrame: at day 90
Secondary outcomes:
measure: Global outcome of four neurologic and disability scores combined
timeFrame: at day 90
Other outcomes:
Locations:
city: Graz
country: Austria
facility: 135.312.43004 Boehringer Ingelheim Investigational Site
city: Innsbruck
country: Austria
facility: 135.312.43007 Boehringer Ingelheim Investigational Site
city: Klagenfurt
country: Austria
facility: 135.312.43010 Boehringer Ingelheim Investigational Site
city: Linz
country: Austria
facility: 135.312.43001 Boehringer Ingelheim Investigational Site
city: Linz
country: Austria
facility: 135.312.43012 Boehringer Ingelheim Investigational Site
city: Linz
country: Austria
facility: 135.312.43013 Boehringer Ingelheim Investigational Site
city: Ma.Gugging/Klosterneuburg
country: Austria
facility: 135.312.43008 Boehringer Ingelheim Investigational Site
city: Salzburg
country: Austria
facility: 135.312.43006 Boehringer Ingelheim Investigational Site
city: St. Pölten
country: Austria
facility: 135.312.43003 Boehringer Ingelheim Investigational Site
city: Wien
country: Austria
facility: 135.312.43002 Boehringer Ingelheim Investigational Site
city: Aalst
country: Belgium
facility: 135.312.32006 O.L. Vrouwziekenhuis
city: Anderlecht
country: Belgium
facility: 135.312.32002 Boehringer Ingelheim Investigational Site
city: Antwerpen
country: Belgium
facility: 135.312.32014 Boehringer Ingelheim Investigational Site
city: Brugge
country: Belgium
facility: 135.312.32001 Boehringer Ingelheim Investigational Site
city: Kortrijk
country: Belgium
facility: 135.312.32011 Boehringer Ingelheim Investigational Site
city: Leuven
country: Belgium
facility: 135.312.32005 Boehringer Ingelheim Investigational Site
city: Yvoir (Godinne)
country: Belgium
facility: 135.312.32016 Boehringer Ingelheim Investigational Site
city: Ostrava-Vitkovice
country: Czech Republic
facility: 135.312.42004 Boehringer Ingelheim Investigational Site
city: Ostrava
country: Czech Republic
facility: 135.312.42001 Boehringer Ingelheim Investigational Site
city: Prague 5
country: Czech Republic
facility: 135.312.42002 Boehringer Ingelheim Investigational Site
city: Aalborg
country: Denmark
facility: 135.312.45005 Boehringer Ingelheim Investigational Site
city: Aarhus
country: Denmark
facility: 135.312.45002 Boehringer Ingelheim Investigational Site
city: Copenhagen NV
country: Denmark
facility: 135.312.45001 Boehringer Ingelheim Investigational Site
city: Glostrup
country: Denmark
facility: 135.312.45004 Boehringer Ingelheim Investigational Site
city: Helsinki
country: Finland
facility: 135.312.35801 Boehringer Ingelheim Investigational Site
city: Kuopio
country: Finland
facility: 135.312.35805 Boehringer Ingelheim Investigational Site
city: Turku
country: Finland
facility: 135.312.35802 Boehringer Ingelheim Investigational Site
city: Auch
country: France
facility: 135.312.33009 Boehringer Ingelheim Investigational Site
city: Besançon cedex
country: France
facility: 135.312.33016 Boehringer Ingelheim Investigational Site
city: Bordeaux cedex
country: France
facility: 135.312.33013 Boehringer Ingelheim Investigational Site
city: Bourg en Bresse
country: France
facility: 135.312.33017 Boehringer Ingelheim Investigational Site
city: Dijon cedex
country: France
facility: 135.312.33008 Boehringer Ingelheim Investigational Site
city: Grenoble cédex 9
country: France
facility: 135.312.33014 Boehringer Ingelheim Investigational Site
city: Lille cedex
country: France
facility: 135.312.33015 Boehringer Ingelheim Investigational Site
city: Limoges cedex 1
country: France
facility: 135.312.33019 Boehringer Ingelheim Investigational Site
city: Lyon Cedex
country: France
facility: 135.312.33001 Boehringer Ingelheim Investigational Site
city: Mantes la Jolie
country: France
facility: 135.312.33024 Boehringer Ingelheim Investigational Site
city: Meaux
country: France
facility: 135.312.33021 Boehringer Ingelheim Investigational Site
city: Montpellier
country: France
facility: 135.312.33002 Boehringer Ingelheim Investigational Site
city: Nancy
country: France
facility: 135.312.33004 Boehringer Ingelheim Investigational Site
city: Nice cedex 1
country: France
facility: 135.312.33003 Boehringer Ingelheim Investigational Site
city: Paris cedex 18
country: France
facility: 135.312.33007 Boehringer Ingelheim Investigational Site
city: Paris
country: France
facility: 135.312.33006 Boehringer Ingelheim Investigational Site
city: Pau cedex
country: France
facility: 135.312.33020 Boehringer Ingelheim Investigational Site
city: Perpignan cedex
country: France
facility: 135.312.33018 Boehringer Ingelheim Investigational Site
city: Pontoise
country: France
facility: 135.312.33023 Boehringer Ingelheim Investigational Site
city: Saint Herblain
country: France
facility: 135.312.33010 Boehringer Ingelheim Investigational Site
city: Toulouse cedex 9
country: France
facility: 135.312.33005 Boehringer Ingelheim Investigational Site
city: Toulouse cedex 9
country: France
facility: 135.312.33012 Boehringer Ingelheim Investigational Site
city: Tours cedex 9
country: France
facility: 135.312.33011 Boehringer Ingelheim Investigational Site
city: Versailles
country: France
facility: 135.312.33022 Boehringer Ingelheim Investigational Site
city: Altenburg
country: Germany
facility: 135.312.49031 Boehringer Ingelheim Investigational Site
city: Bamberg
country: Germany
facility: 135.312.49011 Boehringer Ingelheim Investigational Site
city: Beeskow
country: Germany
facility: 135.312.49037 Boehringer Ingelheim Investigational Site
city: Bochum
country: Germany
facility: 135.312.49017 Boehringer Ingelheim Investigational Site
city: Frankfurt/Main
country: Germany
facility: 135.312.49038 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 135.312.49041 Boehringer Ingelheim Investigational Site
city: Hannover
country: Germany
facility: 135.312.49023 Boehringer Ingelheim Investigational Site
city: Heidelberg
country: Germany
facility: 135.312.49001 Boehringer Ingelheim Investigational Site
city: Köln
country: Germany
facility: 135.312.49008 Boehringer Ingelheim Investigational Site
city: Leipzig
country: Germany
facility: 135.312.49014 Boehringer Ingelheim Investigational Site
city: Ludwigshafen am Rhein
country: Germany
facility: 135.312.49020 Boehringer Ingelheim Investigational Site
city: Magdeburg
country: Germany
facility: 135.312.49004 Boehringer Ingelheim Investigational Site
city: Mainz
country: Germany
facility: 135.312.49003 Boehringer Ingelheim Investigational Site
city: Mannheim
country: Germany
facility: 135.312.49018 Boehringer Ingelheim Investigational Site
city: Minden
country: Germany
facility: 135.312.49002 Boehringer Ingelheim Investigational Site
city: München
country: Germany
facility: 135.312.49006 Boehringer Ingelheim Investigational Site
city: Siegen
country: Germany
facility: 135.312.49005 Boehringer Ingelheim Investigational Site
city: Teupitz
country: Germany
facility: 135.312.49025 Boehringer Ingelheim Investigational Site
city: Wiesbaden
country: Germany
facility: 135.312.49009 Boehringer Ingelheim Investigational Site
city: Athens
country: Greece
facility: 135.312.30004 Boehringer Ingelheim Investigational Site
city: Larissa
country: Greece
facility: 135.312.30005 Boehringer Ingelheim Investigational Site
city: Thessaloniki
country: Greece
facility: 135.312.30002 Boehringer Ingelheim Investigational Site
city: Debrecen
country: Hungary
facility: 135.312.36002 University of Debrecen
city: Györ
country: Hungary
facility: 135.312.36001 Aladár Petz County Hospital
city: Miskolc
country: Hungary
facility: 135.312.36006 BAZ County and Teaching Hospital
city: Coppito (aq)
country: Italy
facility: 135.312.39020 Università degli Studi
city: Firenze
country: Italy
facility: 135.312.39013 A. O. Universitaria di Careggi
city: Firenze
country: Italy
facility: 135.312.39019 Ospedale Santa Maria Annunziata
city: Imperia
country: Italy
facility: 135.312.39022 Ospedale di Imperia
city: Milano
country: Italy
facility: 135.312.39024 Istituto Scientifico San Raffaele
city: Padova
country: Italy
facility: 135.312.39002 A. O. di Padova - Policlinico Universitario
city: Perugia
country: Italy
facility: 135.312.39005 A. O. di Perugia - Policlinico Monteluce
city: Piacenza
country: Italy
facility: 135.312.39023 P. O. di Piacenza
city: Pietra Ligure (sv)
country: Italy
facility: 135.312.39016 A. O. Ospedale Santa Corona
city: Pisa
country: Italy
facility: 135.312.39006 Ospedale Santa Chiara
city: Reggio Emilia
country: Italy
facility: 135.312.39003 A. O. Arcispedale "Santa Maria Nuova"
city: Roma
country: Italy
facility: 135.312.39001 A. O. Policlinico Umberto I
city: Roma
country: Italy
facility: 135.312.39025 Università di Roma "La Sapienza"
city: Udine
country: Italy
facility: 135.312.39018 Ospedale S. Maria della Misericordia
city: Verona
country: Italy
facility: 135.312.39009 Ospedale Maggiore di BorgoTrento
city: Vicenza
country: Italy
facility: 135.312.39004 Ospedale Civile
city: Amsterdam
country: Netherlands
facility: 135.312.31001
city: Enschede
country: Netherlands
facility: 135.312.31007 Medisch Spectrum Twente
city: Bergen
country: Norway
facility: 135.312.47001 Boehringer Ingelheim Investigational Site
city: Trondheim
country: Norway
facility: 135.312.47003 Boehringer Ingelheim Investigational Site
city: Tønsberg
country: Norway
facility: 135.312.47006 Boehringer Ingelheim Investigational Site
city: Gdansk
country: Poland
facility: 135.312.48004 Medical University of Gdansk
city: Katowice
country: Poland
facility: 135.312.48005 Dept. of Neurology, Regenerative and Cerebrovascular Disease
city: Opole
country: Poland
facility: 135.312.48006 Wojewodship Specialistic Neuropsychiatric Centre in Opole
city: Warsaw
country: Poland
facility: 135.312.48001 Institute of Psychiatry & Neurology in Warsaw
city: Warsaw
country: Poland
facility: 135.312.48002 Dr. Anna Gostynska Wolski Hospital
city: Coimbra
country: Portugal
facility: 135.312.35101 Hospitais da Universidade de Coimbra
city: Lisboa
country: Portugal
facility: 135.312.35106 Hospital de Santa Maria
city: Porto
country: Portugal
facility: 135.312.35102 Hospital de Santo António
city: Santa Maria da Feira
country: Portugal
facility: 135.312.35105 Hospital de São Sebastião, EPE
city: Bratislava
country: Slovakia
facility: 135.312.42103 NEURON PLUS s.r.o
city: Levoca
country: Slovakia
facility: 135.312.42102 Hospital Levoca
city: Martin
country: Slovakia
facility: 135.312.42104 Jessenius Faculty of Medicine Commenius University
city: Nitra
country: Slovakia
facility: 135.312.42101 Faculty Hospital
city: Trnava
country: Slovakia
facility: 135.312.42105 Boehringer Ingelheim Investigational Site
city: Albacete
country: Spain
facility: 135.312.34019 Boehringer Ingelheim Investigational Site
city: Badalona / Barcelona
country: Spain
facility: 135.312.34006 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 135.312.34001 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 135.312.34002 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 135.312.34003 Boehringer Ingelheim Investigational Site
city: Bilbao
country: Spain
facility: 135.312.34011 Boehringer Ingelheim Investigational Site
city: Girona
country: Spain
facility: 135.312.34007 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 135.312.34009 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 135.312.34010 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 135.312.34020 Boehringer Ingelheim Investigational Site
city: Santiago de Compostela
country: Spain
facility: 135.312.34017 Boehringer Ingelheim Investigational Site
city: Sevilla
country: Spain
facility: 135.312.34018 Boehringer Ingelheim Investigational Site
city: Zaragoza
country: Spain
facility: 135.312.34014 Boehringer Ingelheim Investigational Site
city: Lidköping
country: Sweden
facility: 135.312.46007 Boehringer Ingelheim Investigational Site
city: Malmö
country: Sweden
facility: 135.312.46003 Boehringer Ingelheim Investigational Site
city: Skövde
country: Sweden
facility: 135.312.46005 Boehringer Ingelheim Investigational Site
city: Stockholm
country: Sweden
facility: 135.312.46002 Boehringer Ingelheim Investigational Site
city: Stockholm
country: Sweden
facility: 135.312.46004 Boehringer Ingelheim Investigational Site
city: Aarau
country: Switzerland
facility: 135.312.41003 Boehringer Ingelheim Investigational Site
city: Basel
country: Switzerland
facility: 135.312.41001 Boehringer Ingelheim Investigational Site
city: Lausanne
country: Switzerland
facility: 135.312.41004 Boehringer Ingelheim Investigational Site
city: St. Gallen
country: Switzerland
facility: 135.312.41002 Boehringer Ingelheim Investigational Site
city: Aberdeen
country: United Kingdom
facility: 135.312.44025 Boehringer Ingelheim Investigational Site
city: Bournemouth
country: United Kingdom
facility: 135.312.44002 Boehringer Ingelheim Investigational Site
city: Cambridge
country: United Kingdom
facility: 135.312.44023 Boehringer Ingelheim Investigational Site
city: Dundee
country: United Kingdom
facility: 135.312.44026 Boehringer Ingelheim Investigational Site
city: Glasgow
country: United Kingdom
facility: 135.312.44003 Boehringer Ingelheim Investigational Site
city: Glasgow
country: United Kingdom
facility: 135.312.44006 Boehringer Ingelheim Investigational Site
city: Glasgow
country: United Kingdom
facility: 135.312.44024 Boehringer Ingelheim Investigational Site
city: Liverpool
country: United Kingdom
facility: 135.312.44018 Boehringer Ingelheim Investigational Site
city: London
country: United Kingdom
facility: 135.312.44030 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Alper BS, Foster G, Thabane L, Rae-Grant A, Malone-Moses M, Manheimer E. Thrombolysis with alteplase 3-4.5 hours after acute ischaemic stroke: trial reanalysis adjusted for baseline imbalances. BMJ Evid Based Med. 2020 Oct;25(5):168-171. doi: 10.1136/bmjebm-2020-111386. Epub 2020 May 19.
citation: Bluhmki E, Chamorro A, Davalos A, Machnig T, Sauce C, Wahlgren N, Wardlaw J, Hacke W. Stroke treatment with alteplase given 3.0-4.5 h after onset of acute ischaemic stroke (ECASS III): additional outcomes and subgroup analysis of a randomised controlled trial. Lancet Neurol. 2009 Dec;8(12):1095-102. doi: 10.1016/S1474-4422(09)70264-9. Epub 2009 Oct 21.
citation: Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos A, Guidetti D, Larrue V, Lees KR, Medeghri Z, Machnig T, Schneider D, von Kummer R, Wahlgren N, Toni D; ECASS Investigators. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008 Sep 25;359(13):1317-29. doi: 10.1056/NEJMoa0804656.