Rt-PA in the Treatment of Acute Ischemic Stroke

Study Overview
=================
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.

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

Conditions
-----------------
Cerebrovascular Accident

Intervention / Treatment
-----------------
* Drug: rt-PA 0.9 mg/kg verum or placebo Intravenous


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: rt-PA 0.9 mg/kg verum or placebo Intravenous|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| modified Rankin scale (mRS) 0-1 (favourable outcome) at Day 90 |  | at day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global outcome of four neurologic and disability scores combined |  | at day 90 |