Multicenter Efficacy Study of Recombinant Human Erythropoietin in Acute Ischemic Stroke

Study Overview
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Brief Summary
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The purpose of this randomized, double-blind, placebo-controlled multicenter study is to determine in a cohort of 506 patients with acute ischemic stroke in the middle cerebral artery territory, the effect of a three-day high-dose, intravenous erythropoietin treatment on functional outcome up to a follow-up of 90 days.

Official Title
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German Multicenter EPO Stroke Trial (Phase II/III)

Conditions
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Infarction, Middle Cerebral Artery, Middle Cerebral Artery Stroke, Stroke, Acute

Intervention / Treatment
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* Drug: recombinant human erythropoietin alfa
* Drug: 0.9% NaCl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ischemic stroke in the middle cerebral artery territory Clearly defined time of onset Confirmed by MRI (DWI, Flair) NIH Stroke Scale ≥ 5 Age > 18 years Treatment within 6h after onset of symptoms Informed consent by patient, relatives or independent physician Life expectancy > 90 days Exclusion Criteria: Coma or precoma (level of consciousness ≥ 2 in NIH Stroke Scale) Previous stroke within the same territory Intracranial or subarachnoidal hemorrhage Traumatic brain injury or brain operation within the last 4 weeks Neoplasia, septic embolism, infectious endocarditis MRI contraindications Renal failure (i.e. dependent on dialysis) Known malignant/life-threatening disease Known myeloproliferative disorder, polycythemia Known allergy or antibodies against erythropoietin Participation in other intervention trials Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br>50ml 0.9% NaCL | Drug: 0.9% NaCl<br>* 50ml 0.9% NaCl iv on 3 consecutive days, starting within 6 hours after onset of symptoms<br>|
| Active Comparator: verum<br>erythropoietin alfa 40,000 IU iv in 50ml 0.9% NaCl | Drug: recombinant human erythropoietin alfa<br>* 40,000 IU in 50ml 0.9% NaCl iv on 3 consecutive days, starting within 6 hours after onset of symptoms<br>* Other names: ERYPO;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurological/functional outcome as measured by the Barthel Index (BI) |  | day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Rankin Scale (mRS) responder |  | day 90 | 
| Barthel Index (BI) |  | day 30 | 
| mRS |  | day30, day 90 | 
| NIH Stroke Scale |  | day 1, 3, 7, 30, 90 | 
| Proportion of subjects with minimal disability (mRS 0-1) |  | day 30, day 90 | 
| All-cause mortality |  | day 90 | 
| Mortality directly related to stroke |  | day 90 | 
| Proportion of subjects with BI >= 95 |  | day 30, day 90 | 
| Proportion of subjects with BI=100 |  | day 30, day 90 | 
| Proportion of subjects with neurological recovery |  | day 3, 7, 30, 90 | 
| Distribution of mRS scores |  | day 30, day 90 | 
| Distribution of BI scores |  | day 30, day 90 | 
| Distribution of NIH Stroke Scale scores |  | day 30, day 90 | 
| Serum level of glial damage markers S100B and GFAP |  | day 1, 2, 3, 4, 7 | 
| Lesion size (MRI DWI, flair) |  | day 1, day 7 | 
| Overall survival |  | day 90 | 
| Late recovery index (BI day 90 versus BI day 30) |  | day 30 to day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stroke, EPO, erythropoietin, ischemia, hypoxia, antiapoptosis, neuroprotection, rtPA, thrombolysis, stroke, middle cerebral artery, Ischemic stroke in the middle cerebral artery territory