rt-PA in the Treatment of Acute Ischemic Stroke

Condition(s) targeted: Cerebrovascular Accident

Intervention: rt-PA 0.9 mg/kg verum or placebo Intravenous (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Boehringer Ingelheim Pharmaceuticals

Official(s) and/or principal investigator(s):
Boehringer Ingelheim Study Coordinator, Study Chair, Affiliation: BI France S.A.S.

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.

Official title: A Placebo Controlled Trial of Alteplase in Acute Ischemic Hemispheric Stroke Where Thrombolysis is Initiated Between 3 and 4.30 Hours After Stroke Onset.

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: mRS 0-1 (favourable outcome) at day 90

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

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 the 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 hemorrhage, 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 hemorrhagic diathesis

- Patients receiving oral anticoagulants.

- Manifest or recent severe or dangerous bleeding

- Known history of or suspected intracranial hemorrhage

- Suspected subarachnoid hemorrhage or condition after subarachnoid hemorrhage from

aneurysm

- History of central nervous system damage (i. e. neoplasm, aneurysm, intracranial or

spinal surgery)

- Hemorrhagic retinopathy,e. g. in diabetes (vision disturbances may indicate hemorrhagic

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

Boehringer Ingelheim Investigational Site, Linz 4020, Austria

Boehringer Ingelheim Investigational Site, St. Polten 3100, Austria

Boehringer Ingelheim Investigational Site, Graz 8036, Austria

Boehringer Ingelheim Investigational Site, Salzburg 5020, Austria

Boehringer Ingelheim Investigational Site, Innsbruck 6020, Austria

Boehringer Ingelheim Investigational Site, Ma.Gugging/Klosterneuburg 3400, Austria

Boehringer Ingelheim Investigational Site, Wien 1130, Austria

Boehringer Ingelheim Investigational Site, Klagenfurt 9020, Austria

Boehringer Ingelheim Investigational Site, Wr. Neustadt 2700, Austria

Boehringer Ingelheim Investigational Site, Linz 4021, Austria

Boehringer Ingelheim Investigational Site, Brugge 8000, Belgium

Boehringer Ingelheim Investigational Site, Anderlecht 1070, Belgium

Boehringer Ingelheim Investigational Site, Montegnee 4420, Belgium

Boehringer Ingelheim Investigational Site, Leuven 3000, Belgium

O.L. Vrouwziekenhuis, Aalst 9300, Belgium

Boehringer Ingelheim Investigational Site, Charleroi 6000, Belgium

Boehringer Ingelheim Investigational Site, Montignies-sur-Sambre 6061, Belgium

Boehringer Ingelheim Investigational Site, Wilrijk 2610, Belgium

Boehringer Ingelheim Investigational Site, Tielt 8700, Belgium

Boehringer Ingelheim Investigational Site, Antwerpen 2018, Belgium

Boehringer Ingelheim Investigational Site, Kortrijk 8500, Belgium

Boehringer Ingelheim Investigational Site, Roeselare 8800, Belgium

Boehringer Ingelheim Investigational Site, Ottignies 1340, Belgium

Boehringer Ingelheim Investigational Site, Bruxelles 1020, Belgium

Boehringer Ingelheim Investigational Site, Yvoir (Godinne) 5530, Belgium

Boehringer Ingelheim Investigational Site, Ostrava 708 52, Czech Republic

Boehringer Ingelheim Investigational Site, Prague 5 150 06, Czech Republic

Boehringer Ingelheim Investigational Site, Ostrava-Vitkovice 703 84, Czech Republic

Boehringer Ingelheim Investigational Site, Zlin 762 75, Czech Republic

Boehringer Ingelheim Investigational Site, Pelhrimov 393 38, Czech Republic

Boehringer Ingelheim Investigational Site, Copenhagen NV 2400, Denmark

Boehringer Ingelheim Investigational Site, Aarhus DK-8000, Denmark

Boehringer Ingelheim Investigational Site, Aalborg 91000, Denmark

Boehringer Ingelheim Investigational Site, Glostrup 2600, Denmark

Boehringer Ingelheim Investigational Site, Helsinki FI-00029 HUS, Finland

Boehringer Ingelheim Investigational Site, Turku FI-20520, Finland

Boehringer Ingelheim Investigational Site, Kuopio FIN-70211, Finland

Boehringer Ingelheim Investigational Site, Lyon Cedex 69394, France

Boehringer Ingelheim Investigational Site, Montpellier 34059, France

Boehringer Ingelheim Investigational Site, Nice cedex 1 06002, France

Boehringer Ingelheim Investigational Site, Nancy 54035, France

Boehringer Ingelheim Investigational Site, Toulouse cedex 9 31059, France

Boehringer Ingelheim Investigational Site, Paris 75674, France

Boehringer Ingelheim Investigational Site, Paris cedex 18 75877, France

Boehringer Ingelheim Investigational Site, Dijon cedex 21033, France

Boehringer Ingelheim Investigational Site, Auch 32008, France

Boehringer Ingelheim Investigational Site, Saint Herblain 44800, France

Boehringer Ingelheim Investigational Site, Tours cedex 9 37044, France

Boehringer Ingelheim Investigational Site, Bordeaux cedex 33076, France

Boehringer Ingelheim Investigational Site, Grenoble cedex 9 38043, France

Boehringer Ingelheim Investigational Site, Lille cedex 59037, France

Boehringer Ingelheim Investigational Site, Besancon cedex 25030, France

Boehringer Ingelheim Investigational Site, Bourg en Bresse 01012, France

Boehringer Ingelheim Investigational Site, Perpignan cedex 66046, France

Boehringer Ingelheim Investigational Site, Limoges cedex 1 87042, France

Boehringer Ingelheim Investigational Site, Pau cedex 64046, France

Boehringer Ingelheim Investigational Site, Meaux 77100, France

Boehringer Ingelheim Investigational Site, Pontoise 95301, France

Boehringer Ingelheim Investigational Site, Versailles 78000, France

Boehringer Ingelheim Investigational Site, Mantes la Jolie 78200, France

Boehringer Ingelheim Investigational Site, Heidelberg 69120, Germany

Boehringer Ingelheim Investigational Site, Minden 32427, Germany

Boehringer Ingelheim Investigational Site, Mainz 55131, Germany

Boehringer Ingelheim Investigational Site, Magdeburg 39120, Germany

Boehringer Ingelheim Investigational Site, Siegen 57076, Germany

Boehringer Ingelheim Investigational Site, Munchen 81545, Germany

Boehringer Ingelheim Investigational Site, Wiesbaden 65199, Germany

Boehringer Ingelheim Investigational Site, Bamberg 96049, Germany

Boehringer Ingelheim Investigational Site, Leipzig 04103, Germany

Boehringer Ingelheim Investigational Site, Bochum 44791, Germany

Boehringer Ingelheim Investigational Site, Mannheim 68135, Germany

Boehringer Ingelheim Investigational Site, Koln 50924, Germany

Boehringer Ingelheim Investigational Site, Ludwigshafen am Rhein 67063, Germany

Boehringer Ingelheim Investigational Site, Aschaffenburg 63739, Germany

Boehringer Ingelheim Investigational Site, Beeskow 15848, Germany

Boehringer Ingelheim Investigational Site, Frankfurt/Main 60488, Germany

Boehringer Ingelheim Investigational Site, Kassel 34125, Germany

Boehringer Ingelheim Investigational Site, Hannover 30167, Germany

Boehringer Ingelheim Investigational Site, Teupitz 15755, Germany

Boehringer Ingelheim Investigational Site, Ingolstadt 85049, Germany

Boehringer Ingelheim Investigational Site, Wurzburg 97080, Germany

Boehringer Ingelheim Investigational Site, Altenburg 04600, Germany

Boehringer Ingelheim Investigational Site, Hamburg 22291, Germany

Boehringer Ingelheim Investigational Site, Thessaloniki 56429, Greece

Boehringer Ingelheim Investigational Site, Athens 15669, Greece

Boehringer Ingelheim Investigational Site, Larissa, Greece

Aladar Petz County Hospital, Gyor 9024, Hungary

University of Debrecen, Debrecen 4012, Hungary

Pest County Flor Ferenc Hospital, Kistarcsa 2143, Hungary

BAZ County and Teaching Hospital, Miskolc 3501, Hungary

A. O. di Padova - Policlinico Universitario, PADOVA 35128, Italy

A. O. Arcispedale "Santa Maria Nuova", REGGIO EMILIA 42100, Italy

Ospedale Civile, VICENZA 36100, Italy

A. O. di Perugia - Policlinico Monteluce, PERUGIA 06126, Italy

Ospedale Santa Chiara, PISA 56100, Italy

Ospedale Maggiore di BorgoTrento, VERONA 37126, Italy

A. O. Ospedale "San Martino" e Cliniche Univ. Conv., GENOVA 16132, Italy

A. O. Policlinico Umberto I, Roma 00185, Italy

A. O. Universitaria di Careggi, Firenze 50122, Italy

Ospedale S. Maria della Misericordia, UDINE 33100, Italy

Ospedale di Imperia, IMPERIA 18100, Italy

P. O. di Piacenza, PIACENZA 29100, Italy

A. O. San Gerardo degli Espositi, MONZA 20100, Italy

A. O. Ospedale Santa Corona, PIETRA LIGURE (SV) 17027, Italy

Ospedale Santa Maria Annunziata, FIRENZE 50131, Italy

Universita degli Studi, COPPITO (AQ) 67010, Italy

Istituto Scientifico San Raffaele, MILANO 20132, Italy

Universita di Roma "La Sapienza", ROMA 00189, Italy

Medisch Spectrum Twente, Enschede 7513 ER, Netherlands

Boehringer Ingelheim Investigational Site, BERGEN N-5021, Norway

Boehringer Ingelheim Investigational Site, NORDBYHAGEN N-1474, Norway

Boehringer Ingelheim Investigational Site, TRONDHEIM N-7006, Norway

Boehringer Ingelheim Investigational Site, T?NSBERG N-3103, Norway

Boehringer Ingelheim Investigational Site, MOLDE N-6407, Norway

Boehringer Ingelheim Investigational Site, KRISTIANSAND N-4604, Norway

Institute of Psychiatry & Neurology in Warsaw, Warsaw 02-958, Poland

Dr. Anna Gostynska Wolski Hospital, Warsaw 01-211, Poland

Department and Clinic of Neurology AM, Warsaw, Warsaw 02-097, Poland

Medical University of Gdansk, Gdansk 80-952, Poland

Dept. of Neurology, Regenerative and Cerebrovascular Disease, Katowice 40-752, Poland

Wojewodship Specialistic Neuropsychiatric Centre in Opole, Opole 45-221, Poland

Hospitais da Universidade de Coimbra, COIMBRA 3000-075, Portugal

Hospital de Santo Antonio, PORTO 4100, Portugal

Servico de Neudologia, Coimbra 3041-853, Portugal

Hospital de S?o Sebasti?o, EPE, Santa Maria da Feira 4520-211, Portugal

Hospital de Santa Maria, Lisboa 1649-035, Portugal

Faculty Hospital, Nitra 949 01, Slovakia

Hospital Levoca, Levoca 054 35, Slovakia

NEURON PLUS s.r.o, Bratislava 851 07, Slovakia

Jessenius Faculty of Medicine Commenius University, Martin 036 59, Slovakia

Boehringer Ingelheim Investigational Site, Trnava 91701, Slovakia

Ciudad Sanitaria Universitaria Vall d'Hebron. Neurology, Barcelona 08035, Spain

Hospital Clinic i Provincial. Neurology, Barcelona 08035, Spain

Hospital de la Santa. Creu i Sant Pau. Neurology, Barcelona 08025, Spain

Hospital del Mar. Neurology, Barcelona 08003, Spain

Hospital Germans Trias i Pujol. Neurology, Badalona / Barcelona 08916, Spain

Hospital de Girona, Dr. Josep Trueta. Neurology, Girona 17007, Spain

Hospital Universitario San Carlos. Neurology, Madrid 28040, Spain

Hospital Universitario de la Princesa. Neurology, Madrid 28006, Spain

Hospital Clinico Lozano Blesa. Neurology, Zaragoza 50009, Spain

Hospital Clinico Universitario de Galicia. Neurology, Santiago de Compostela 15706, Spain

Hospital Universitario Virgen del Rocio. Neurology, Sevilla 41013, Spain

Hospital de Basurto. Neurology, Bilbao 48013, Spain

Hospital general Universitario de Albacete. Neurology, Albacete 02006, Spain

Hospital Ramon y Cajal. Neurology, Madrid 28034, Spain

Boehringer Ingelheim Investigational Site, Stockholm 171 76, Sweden

Boehringer Ingelheim Investigational Site, Malmo 205 02, Sweden

Boehringer Ingelheim Investigational Site, Stockholm 118 83, Sweden

Boehringer Ingelheim Investigational Site, Skovde 541 85, Sweden

Boehringer Ingelheim Investigational Site, Lidkoping 531 85, Sweden

Boehringer Ingelheim Investigational Site, Basel 4031, Switzerland

Boehringer Ingelheim Investigational Site, St. Gallen 9007, Switzerland

Boehringer Ingelheim Investigational Site, Aarau 5001, Switzerland

Boehringer Ingelheim Investigational Site, Lausanne 1011, Switzerland

Boehringer Ingelheim Investigational Site, Solothurn 4500, Switzerland

Boehringer Ingelheim Investigational Site, Bournemouth BH7 7DW, United Kingdom

Boehringer Ingelheim Investigational Site, Glasgow G21 3UW, United Kingdom

Boehringer Ingelheim Investigational Site, Glasgow G51 4TF, United Kingdom

Boehringer Ingelheim Investigational Site, Liverpool L9 7AL, United Kingdom

Boehringer Ingelheim Investigational Site, Cambridge CB2 2QQ, United Kingdom

Boehringer Ingelheim Investigational Site, Glasgow G11 6NT, United Kingdom

Boehringer Ingelheim Investigational Site, Aberdeen AB25 2ZN, United Kingdom

Boehringer Ingelheim Investigational Site, Dundee DD1 9SY, United Kingdom

Boehringer Ingelheim Investigational Site, London SW17 9RF, United Kingdom

Ending date: February 2008
Last updated: April 1, 2008