Rt-PA in the Treatment of Acute Ischemic Stroke

Cerebrovascular Accident Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00153036
• Other study ID #: 135.312
• Status: Completed
• Phase: Phase 3
• First received: September 9, 2005
• Last updated: April 30, 2014
• Start date: April 2003

Study information

• Verified date: April 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Bundesministerium fuer Gesundheit und FrauenBelgium: Federal Agency for Medicines and Health Products, FAMHPCzech Republic: State Institute for Drug Control (SUKL), CZ-100 41 Prague 10Denmark: Danish Medicines AgencyFinland: Finnish Medicines AgencyFrance: AFSSAPSGermany: Bundesinstitut fuer Arzneimittel und Medizinprodukte BfArmGreat Britain: MHRAGreece: HELLENIC REPUBLIC MINISTRY OF HEALTH AND WELFAREHungary: National Institute of Pharmacy, H-1051 BudapestItaly: Comitato Etico Policlinico Umberto I - Università degli Studi di Roma La SapienzaNetherlands: Academical Medical CentreNorway: Norwegian Medicines Agency (Statens Legemiddelverk)Poland: Urzad Rejestracji Produktow Leczniczych, Wyrobow, Medycznych i Produktow Biobojczych, PL-00725 WarsawPortugal: INFARMED, National Authority of Medicines and Health Products, IPSlovakia: SUKL (state institute for drug control), SK-825 08 Bratislava 26Spain: Agencia Española de Medicamentos y Productos SantariosSweden: Medical Product AgencySwitzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 821
• Est. primary completion date: February 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cerebrovascular Accident
• Stroke

Intervention

Drug:
• rt-PA 0.9 mg/kg verum or placebo Intravenous

Locations

Country	Name	City	State
Austria	135.312.43004 Boehringer Ingelheim Investigational Site	Graz
Austria	135.312.43007 Boehringer Ingelheim Investigational Site	Innsbruck
Austria	135.312.43010 Boehringer Ingelheim Investigational Site	Klagenfurt
Austria	135.312.43001 Boehringer Ingelheim Investigational Site	Linz
Austria	135.312.43012 Boehringer Ingelheim Investigational Site	Linz
Austria	135.312.43013 Boehringer Ingelheim Investigational Site	Linz
Austria	135.312.43008 Boehringer Ingelheim Investigational Site	Ma.Gugging/Klosterneuburg
Austria	135.312.43006 Boehringer Ingelheim Investigational Site	Salzburg
Austria	135.312.43003 Boehringer Ingelheim Investigational Site	St. Pölten
Austria	135.312.43002 Boehringer Ingelheim Investigational Site	Wien
Belgium	135.312.32006 O.L. Vrouwziekenhuis	Aalst
Belgium	135.312.32002 Boehringer Ingelheim Investigational Site	Anderlecht
Belgium	135.312.32014 Boehringer Ingelheim Investigational Site	Antwerpen
Belgium	135.312.32001 Boehringer Ingelheim Investigational Site	Brugge
Belgium	135.312.32011 Boehringer Ingelheim Investigational Site	Kortrijk
Belgium	135.312.32005 Boehringer Ingelheim Investigational Site	Leuven
Belgium	135.312.32016 Boehringer Ingelheim Investigational Site	Yvoir (Godinne)
Czech Republic	135.312.42001 Boehringer Ingelheim Investigational Site	Ostrava
Czech Republic	135.312.42004 Boehringer Ingelheim Investigational Site	Ostrava-Vitkovice
Czech Republic	135.312.42002 Boehringer Ingelheim Investigational Site	Prague 5
Denmark	135.312.45005 Boehringer Ingelheim Investigational Site	Aalborg
Denmark	135.312.45002 Boehringer Ingelheim Investigational Site	Aarhus
Denmark	135.312.45001 Boehringer Ingelheim Investigational Site	Copenhagen NV
Denmark	135.312.45004 Boehringer Ingelheim Investigational Site	Glostrup
Finland	135.312.35801 Boehringer Ingelheim Investigational Site	Helsinki
Finland	135.312.35805 Boehringer Ingelheim Investigational Site	Kuopio
Finland	135.312.35802 Boehringer Ingelheim Investigational Site	Turku
France	135.312.33009 Boehringer Ingelheim Investigational Site	Auch
France	135.312.33016 Boehringer Ingelheim Investigational Site	Besançon cedex
France	135.312.33013 Boehringer Ingelheim Investigational Site	Bordeaux cedex
France	135.312.33017 Boehringer Ingelheim Investigational Site	Bourg en Bresse
France	135.312.33008 Boehringer Ingelheim Investigational Site	Dijon cedex
France	135.312.33014 Boehringer Ingelheim Investigational Site	Grenoble cédex 9
France	135.312.33015 Boehringer Ingelheim Investigational Site	Lille cedex
France	135.312.33019 Boehringer Ingelheim Investigational Site	Limoges cedex 1
France	135.312.33001 Boehringer Ingelheim Investigational Site	Lyon Cedex
France	135.312.33024 Boehringer Ingelheim Investigational Site	Mantes la Jolie
France	135.312.33021 Boehringer Ingelheim Investigational Site	Meaux
France	135.312.33002 Boehringer Ingelheim Investigational Site	Montpellier
France	135.312.33004 Boehringer Ingelheim Investigational Site	Nancy
France	135.312.33003 Boehringer Ingelheim Investigational Site	Nice cedex 1
France	135.312.33006 Boehringer Ingelheim Investigational Site	Paris
France	135.312.33007 Boehringer Ingelheim Investigational Site	Paris cedex 18
France	135.312.33020 Boehringer Ingelheim Investigational Site	Pau cedex
France	135.312.33018 Boehringer Ingelheim Investigational Site	Perpignan cedex
France	135.312.33023 Boehringer Ingelheim Investigational Site	Pontoise
France	135.312.33010 Boehringer Ingelheim Investigational Site	Saint Herblain
France	135.312.33005 Boehringer Ingelheim Investigational Site	Toulouse cedex 9
France	135.312.33012 Boehringer Ingelheim Investigational Site	Toulouse cedex 9
France	135.312.33011 Boehringer Ingelheim Investigational Site	Tours cedex 9
France	135.312.33022 Boehringer Ingelheim Investigational Site	Versailles
Germany	135.312.49031 Boehringer Ingelheim Investigational Site	Altenburg
Germany	135.312.49011 Boehringer Ingelheim Investigational Site	Bamberg
Germany	135.312.49037 Boehringer Ingelheim Investigational Site	Beeskow
Germany	135.312.49017 Boehringer Ingelheim Investigational Site	Bochum
Germany	135.312.49038 Boehringer Ingelheim Investigational Site	Frankfurt/Main
Germany	135.312.49041 Boehringer Ingelheim Investigational Site	Hamburg
Germany	135.312.49023 Boehringer Ingelheim Investigational Site	Hannover
Germany	135.312.49001 Boehringer Ingelheim Investigational Site	Heidelberg
Germany	135.312.49008 Boehringer Ingelheim Investigational Site	Köln
Germany	135.312.49014 Boehringer Ingelheim Investigational Site	Leipzig
Germany	135.312.49020 Boehringer Ingelheim Investigational Site	Ludwigshafen am Rhein
Germany	135.312.49004 Boehringer Ingelheim Investigational Site	Magdeburg
Germany	135.312.49003 Boehringer Ingelheim Investigational Site	Mainz
Germany	135.312.49018 Boehringer Ingelheim Investigational Site	Mannheim
Germany	135.312.49002 Boehringer Ingelheim Investigational Site	Minden
Germany	135.312.49006 Boehringer Ingelheim Investigational Site	München
Germany	135.312.49005 Boehringer Ingelheim Investigational Site	Siegen
Germany	135.312.49025 Boehringer Ingelheim Investigational Site	Teupitz
Germany	135.312.49009 Boehringer Ingelheim Investigational Site	Wiesbaden
Greece	135.312.30004 Boehringer Ingelheim Investigational Site	Athens
Greece	135.312.30005 Boehringer Ingelheim Investigational Site	Larissa
Greece	135.312.30002 Boehringer Ingelheim Investigational Site	Thessaloniki
Hungary	135.312.36002 University of Debrecen	Debrecen
Hungary	135.312.36001 Aladár Petz County Hospital	Györ
Hungary	135.312.36006 BAZ County and Teaching Hospital	Miskolc
Italy	135.312.39020 Università degli Studi	Coppito (aq)
Italy	135.312.39013 A. O. Universitaria di Careggi	Firenze
Italy	135.312.39019 Ospedale Santa Maria Annunziata	Firenze
Italy	135.312.39022 Ospedale di Imperia	Imperia
Italy	135.312.39024 Istituto Scientifico San Raffaele	Milano
Italy	135.312.39002 A. O. di Padova - Policlinico Universitario	Padova
Italy	135.312.39005 A. O. di Perugia - Policlinico Monteluce	Perugia
Italy	135.312.39023 P. O. di Piacenza	Piacenza
Italy	135.312.39016 A. O. Ospedale Santa Corona	Pietra Ligure (sv)
Italy	135.312.39006 Ospedale Santa Chiara	Pisa
Italy	135.312.39003 A. O. Arcispedale "Santa Maria Nuova"	Reggio Emilia
Italy	135.312.39001 A. O. Policlinico Umberto I	Roma
Italy	135.312.39025 Università di Roma "La Sapienza"	Roma
Italy	135.312.39018 Ospedale S. Maria della Misericordia	Udine
Italy	135.312.39009 Ospedale Maggiore di BorgoTrento	Verona
Italy	135.312.39004 Ospedale Civile	Vicenza
Netherlands	135.312.31001	Amsterdam
Netherlands	135.312.31007 Medisch Spectrum Twente	Enschede
Norway	135.312.47001 Boehringer Ingelheim Investigational Site	Bergen
Norway	135.312.47006 Boehringer Ingelheim Investigational Site	Tønsberg
Norway	135.312.47003 Boehringer Ingelheim Investigational Site	Trondheim
Poland	135.312.48004 Medical University of Gdansk	Gdansk
Poland	135.312.48005 Dept. of Neurology, Regenerative and Cerebrovascular Disease	Katowice
Poland	135.312.48006 Wojewodship Specialistic Neuropsychiatric Centre in Opole	Opole
Poland	135.312.48001 Institute of Psychiatry & Neurology in Warsaw	Warsaw
Poland	135.312.48002 Dr. Anna Gostynska Wolski Hospital	Warsaw
Portugal	135.312.35101 Hospitais da Universidade de Coimbra	Coimbra
Portugal	135.312.35106 Hospital de Santa Maria	Lisboa
Portugal	135.312.35102 Hospital de Santo António	Porto
Portugal	135.312.35105 Hospital de São Sebastião, EPE	Santa Maria da Feira
Slovakia	135.312.42103 NEURON PLUS s.r.o	Bratislava
Slovakia	135.312.42102 Hospital Levoca	Levoca
Slovakia	135.312.42104 Jessenius Faculty of Medicine Commenius University	Martin
Slovakia	135.312.42101 Faculty Hospital	Nitra
Slovakia	135.312.42105 Boehringer Ingelheim Investigational Site	Trnava
Spain	135.312.34019 Boehringer Ingelheim Investigational Site	Albacete
Spain	135.312.34006 Boehringer Ingelheim Investigational Site	Badalona / Barcelona
Spain	135.312.34001 Boehringer Ingelheim Investigational Site	Barcelona
Spain	135.312.34002 Boehringer Ingelheim Investigational Site	Barcelona
Spain	135.312.34003 Boehringer Ingelheim Investigational Site	Barcelona
Spain	135.312.34011 Boehringer Ingelheim Investigational Site	Bilbao
Spain	135.312.34007 Boehringer Ingelheim Investigational Site	Girona
Spain	135.312.34009 Boehringer Ingelheim Investigational Site	Madrid
Spain	135.312.34010 Boehringer Ingelheim Investigational Site	Madrid
Spain	135.312.34020 Boehringer Ingelheim Investigational Site	Madrid
Spain	135.312.34017 Boehringer Ingelheim Investigational Site	Santiago de Compostela
Spain	135.312.34018 Boehringer Ingelheim Investigational Site	Sevilla
Spain	135.312.34014 Boehringer Ingelheim Investigational Site	Zaragoza
Sweden	135.312.46007 Boehringer Ingelheim Investigational Site	Lidköping
Sweden	135.312.46003 Boehringer Ingelheim Investigational Site	Malmö
Sweden	135.312.46005 Boehringer Ingelheim Investigational Site	Skövde
Sweden	135.312.46002 Boehringer Ingelheim Investigational Site	Stockholm
Sweden	135.312.46004 Boehringer Ingelheim Investigational Site	Stockholm
Switzerland	135.312.41003 Boehringer Ingelheim Investigational Site	Aarau
Switzerland	135.312.41001 Boehringer Ingelheim Investigational Site	Basel
Switzerland	135.312.41004 Boehringer Ingelheim Investigational Site	Lausanne
Switzerland	135.312.41002 Boehringer Ingelheim Investigational Site	St. Gallen
United Kingdom	135.312.44025 Boehringer Ingelheim Investigational Site	Aberdeen
United Kingdom	135.312.44002 Boehringer Ingelheim Investigational Site	Bournemouth
United Kingdom	135.312.44023 Boehringer Ingelheim Investigational Site	Cambridge
United Kingdom	135.312.44026 Boehringer Ingelheim Investigational Site	Dundee
United Kingdom	135.312.44003 Boehringer Ingelheim Investigational Site	Glasgow
United Kingdom	135.312.44006 Boehringer Ingelheim Investigational Site	Glasgow
United Kingdom	135.312.44024 Boehringer Ingelheim Investigational Site	Glasgow
United Kingdom	135.312.44018 Boehringer Ingelheim Investigational Site	Liverpool
United Kingdom	135.312.44030 Boehringer Ingelheim Investigational Site	London

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Austria,  Belgium,  Czech Republic,  Denmark,  Finland,  France,  Germany,  Greece,  Hungary,  Italy,  Netherlands,  Norway,  Poland,  Portugal,  Slovakia,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	modified Rankin scale (mRS) 0-1 (favourable outcome) at Day 90		at day 90	No
Secondary	Global outcome of four neurologic and disability scores combined		at day 90	No

External Links

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