Clinical trial NCT00604630: Multicenter Efficacy Study of Recombinant Human Erythropoietin in Acute Ischemic Stroke
Official title: German Multicenter EPO Stroke Trial (Phase II/III)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Infarction, Middle Cerebral Artery
Middle Cerebral Artery Stroke
Stroke, Acute
Keywords: stroke
EPO
erythropoietin
ischemia
hypoxia
antiapoptosis
neuroprotection
rtPA
thrombolysis
stroke, middle cerebral artery
Ischemic stroke in the middle cerebral artery territory
Lead sponsor: Max-Planck-Institute of Experimental Medicine
Sponsor class: OTHER
Collaborators: name: Johnson & Johnson
name: Parexel
First posted: 2008-01-30
Enrollment: 522
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Neurological/functional outcome as measured by the Barthel Index (BI)
timeFrame: day 90
Secondary outcomes:
measure: Modified Rankin Scale (mRS) responder
timeFrame: day 90
measure: Barthel Index (BI)
timeFrame: day 30
measure: mRS
timeFrame: day30, day 90
measure: NIH Stroke Scale
timeFrame: day 1, 3, 7, 30, 90
measure: Proportion of subjects with minimal disability (mRS 0-1)
timeFrame: day 30, day 90
measure: All-cause mortality
timeFrame: day 90
measure: Mortality directly related to stroke
timeFrame: day 90
measure: Proportion of subjects with BI >= 95
timeFrame: day 30, day 90
measure: Proportion of subjects with BI=100
timeFrame: day 30, day 90
measure: Proportion of subjects with neurological recovery
timeFrame: day 3, 7, 30, 90
measure: Distribution of mRS scores
timeFrame: day 30, day 90
measure: Distribution of BI scores
timeFrame: day 30, day 90
measure: Distribution of NIH Stroke Scale scores
timeFrame: day 30, day 90
measure: Serum level of glial damage markers S100B and GFAP
timeFrame: day 1, 2, 3, 4, 7
measure: Lesion size (MRI DWI, flair)
timeFrame: day 1, day 7
measure: Overall survival
timeFrame: day 90
measure: Late recovery index (BI day 90 versus BI day 30)
timeFrame: day 30 to day 90
Other outcomes:
Locations:
city: Braunschweig
country: Germany
facility: Neurologische Klinik des Städtischen Klinikums Braunschweig
city: Bremen
country: Germany
facility: Neurologische Klink, Klinikum Bremen-Mitte
city: Celle
country: Germany
facility: Neurologische Klinik, Allgemeines Krankenhaus Celle
city: Dresden
country: Germany
facility: Klinik und Poliklinik für Neurologie, Universitätsklinikum Carl Gustav Carus der TU Dresden
city: Erlangen
country: Germany
facility: Neurologische Klinik, Universität Erlangen-Nürnberg
city: Essen
country: Germany
facility: Klinik für Neurologie, Universität Essen
city: Goettingen
country: Germany
facility: Neurologische Universitätsklinik der Georg-August-Universität Goettingen
city: Hannover
country: Germany
facility: Neurologische Klinik, Medizinische Hochschule Hannover
city: Leipzig
country: Germany
facility: Klinik und Poliklinik für Neurologie der Universität Leipzig
Study officials:
References:
citation: Siren AL, Fratelli M, Brines M, Goemans C, Casagrande S, Lewczuk P, Keenan S, Gleiter C, Pasquali C, Capobianco A, Mennini T, Heumann R, Cerami A, Ehrenreich H, Ghezzi P. Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress. Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):4044-9. doi: 10.1073/pnas.051606598. Epub 2001 Mar 20.
citation: Ehrenreich H, Hasselblatt M, Dembowski C, Cepek L, Lewczuk P, Stiefel M, Rustenbeck HH, Breiter N, Jacob S, Knerlich F, Bohn M, Poser W, Ruther E, Kochen M, Gefeller O, Gleiter C, Wessel TC, De Ryck M, Itri L, Prange H, Cerami A, Brines M, Siren AL. Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med. 2002 Aug;8(8):495-505.
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citation: Siren AL, Radyushkin K, Boretius S, Kammer D, Riechers CC, Natt O, Sargin D, Watanabe T, Sperling S, Michaelis T, Price J, Meyer B, Frahm J, Ehrenreich H. Global brain atrophy after unilateral parietal lesion and its prevention by erythropoietin. Brain. 2006 Feb;129(Pt 2):480-9. doi: 10.1093/brain/awh703. Epub 2005 Dec 9.
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citation: Ehrenreich H, Fischer B, Norra C, Schellenberger F, Stender N, Stiefel M, Siren AL, Paulus W, Nave KA, Gold R, Bartels C. Exploring recombinant human erythropoietin in chronic progressive multiple sclerosis. Brain. 2007 Oct;130(Pt 10):2577-88. doi: 10.1093/brain/awm203. Epub 2007 Aug 29.
citation: Woywodt A, Gerdes S, Ahl B, Erdbruegger U, Haubitz M, Weissenborn K. Circulating endothelial cells and stroke: influence of stroke subtypes and changes during the course of disease. J Stroke Cerebrovasc Dis. 2012 Aug;21(6):452-8. doi: 10.1016/j.jstrokecerebrovasdis.2010.11.003.
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