European Cooperative Acute Stroke Study-4: Extending the time for thrombolysis in emergency neurological deficits
| ISRCTN | ISRCTN71616222 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN71616222 |
| EudraCT/CTIS number | 2012-003609-80 |
| Secondary identifying numbers | Version 1.0, 15 May 2013 |
- Submission date
- 17/07/2013
- Registration date
- 22/10/2013
- Last edited
- 08/04/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Plain English Summary
Background and study aims
The only approved medical treatment for stroke patients is thrombolysis treatment (dissolving blood clots) with the drug Alteplase within a 4.5-hour time-window from the start of symptoms. Thus patients with a longer or unknown time-window cannot be treated with Alteplase. This study aims to find out about the beneficial effect of treatment with Alteplase in such patients based on a careful selection with MRI techniques.
Who can participate?
Patients with symptoms of an acute stroke between 4.5 and 9 hours after symptom onset or with unknown time-window (e.g. waking up with symptoms).
What does the study involve?
Patients will be randomly allocated to either receive Alteplase or placebo (dummy). The drug or the placebo will be injected through their veins for one hour. Patients will be followed up at 3 months.
What are the possible benefits and risks of participating?
Possible benefits are reduced disability because of the reduction of the stroke size. The main risk of any thrombolytic therapy is hemorrhage with deterioration of the nervous system.
Where is the study run from?
Around 30 centers in Austria, Czech Republic, France, Germany, Italy, Spain and the UK will participate.
When is the study starting and how long is it expected to run for?
The study will start in late 2014 and run until 2016.
Who is funding the study?
This study is funded by Boehringer Ingelheim (Germany).
Who is the main contact?
Prof. Dr Werner Hacke
Neurologie@med.uni-heidelberg.de
Contact information
Scientific
Head of Neurology
University hospital Heidelberg
Im Neuenheimer Feld 400
Heidelberg
69120
Germany
Study information
| Study design | Double-blind placebo-controlled randomized multi-center study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | European Cooperative Acute Stroke Study-4: Extending the time for thrombolysis in emergency neurological deficits a double-blind, placebo-controlled randomized study |
| Study acronym | ECASS 4 |
| Study hypothesis | To test the hypothesis that ischemic stroke patients with significant penumbral mismatch at 4.5-9 hours post onset of stroke or after waking with symptoms of stroke ("wake up stroke") will have improved clinical outcomes when given intravenous rt-PA (alteplase) compared to patients treated with placebo. |
| Ethics approval(s) | For Germany (which is the lead country) ethics committee of the Medical Faculty of the University Hospital Heidelberg; 20/09/2013; Ref: AFmu-328/2013 |
| Condition | Stroke |
| Intervention | Patients will be randomized on a 1:1 basis to either receive Alteplase (0.9 mg/kg bw, not more than 90 mg) or placebo. Route of intervention: Intravenous (iv.) Duration: 1 hour Follow-up: 3 months |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Alteplase |
| Primary outcome measure | Categorical shift in the modified Rankin Scale (mRS) at day 90 |
| Secondary outcome measures | 1. Disability at day 90, dichotomized as a favorable outcome (mRS) 0-1 vs 2 - 6 2. Change in at least 11 National Institute of Health Stroke Scale (NIHSS) points or reaching 0 or 1 on this scale at day 1 and day 90 3. Reperfusion at 12-24 hours after treatment 4. Recanalization at 12-24 hours after treatment 5. Infarct growth on diffusion-weighted imaging (DWI) within 12-24 hours after treatment 6. NIHSS score at day 7 7. Barthel Index (BI) at day 90 8. Montreal Cognitive Assessment (MoCA) score at day 90 |
| Overall study start date | 01/09/2013 |
| Overall study end date | 31/08/2016 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 264 |
| Participant inclusion criteria | 1. Patients presenting with acute ischemic stroke 2. Patient or legally acceptable representative has given written informed consent. An independent witness may sign the consent form if the patient is able to give verbal consent but unable to sign 3. Patients, male and female, aged 18 years or over 4. Treatment onset within 4.5 and 9 hours after stroke onset or patients waking up with stroke symptoms and unclear time window 5. National Institutes of Health Stroke Scale (NIHSS) score of 4 to 26 with clinical signs of hemispheric infarction 6. Penumbral mismatch imaging via local assessment following predefined criteria using standardized criteria including a perfusion volume (PWI) to infarct core (DWI) ratio of ≥ 1.2, and a minimum perfusion lesion volume of 20 ml |
| Participant exclusion criteria | 1. Intracranial hemorrhage (ICH) identified by CT or MRI 2. Rapidly improving symptoms, particularly if, in the opinion of the investigator, the improvement is likely to result in the patient having an NIHSS score of <4 at randomization 3. Pre-stroke modified Rankin Scale (mRS) score of >1 (indicating previous disability) 4. Contraindication to imaging with MRI 5. Infarct core >1/3 MCA territory qualitatively or >100 ml quantitatively (determined by DWI lesion on MRI) 6. Participation in any investigational study in the previous 30 days 7. A life expectancy of less than 3 months 8. Any condition that, in the opinion of the investigator, could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study (this applies to patients with severe microangiopathy such as hemolytic uremic syndrome or thrombotic thrombocytopenic purpura) 9. Pregnant (clinically evident) or breastfeeding women 10. Previous stroke within the three months prior to randomization 11. Recent history (in the opinion of the investigator) or clinical presentation of ICH, subarachnoid hemorrhage (SAH), arterio-venous (AV) malformation, aneurysm or cerebral neoplasm 12. Current use of oral anticoagulants and a prolonged prothrombin time (INR > 1.6) or any activated partial thromboplastin (aPTT) time exceeding 1.5-times the normal range or prolonged Thrombin-Time (TT), indicating the potential use of Dabigatran-Etexilate 13. Use of heparin, except for low-dose subcutaneous heparin, within 48 hours prior to randomization 14. Use of glycoprotein IIb-IIIa inhibitors within 72 hours prior to randomization 15. Clinically significant hypoglycemia 16. Uncontrolled hypertension defined by blood pressure > 185 mmHg systolic or >110 mmHg diastolic on at least two separate occasions at least 10 minutes apart, or requiring aggressive treatment to reduce the blood pressure to within these limits. The definition of aggressive treatment is left to the discretion of the investigator 17. Hereditary or acquired hemorrhagic diathesis 18. Gastrointestinal or urinary bleeding within 21 days prior to randomization 19. Major surgery within 14 days prior to randomization which poses a risk in the opinion of the investigator 20. Exposure to a thrombolytic agent within 72 hours prior to randomization |
| Recruitment start date | 01/09/2013 |
| Recruitment end date | 31/08/2016 |
Locations
Countries of recruitment
- Czech Republic
- France
- Germany
- Italy
- United Kingdom
Study participating centre
69120
Germany
Sponsor information
University/education
Medical Faculty
Represented by Universitätsklinikum Heidelberg and its Commercial Director Ms. Irmtraut Gürkan
Im Neuenheimer Feld 672
Heidelberg
69120
Germany
| Website | http://www.uni-heidelberg.de |
|---|---|
"ROR" |
https://ror.org/038t36y30 |
Funders
Funder type
Industry
Private sector organisation / For-profit companies (industry)
- Alternative name(s)
- Boehringer Ingelheim Pharmaceuticals, Inc., Boehringer Ingelheim International GmbH, BI, BIPI
- Location
- United States of America
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/07/2019 | Yes | No |
Editorial Notes
08/04/2019: Publication reference added.
