Double-Blind, Placebo-Controlled Multicenter Efficacy Study of Recombinant Human Erythropoietin in Acute Ischemic Stroke

Condition(s) targeted: Infarction, Middle Cerebral Artery; Middle Cerebral Artery Stroke; Stroke, Acute

Intervention: recombinant human erythropoietin alfa (Drug); 0.9% NaCl (Drug)

Phase: Phase 2/Phase 3

Status: Active, not recruiting

Sponsored by: Max-Planck-Institute of Experimental Medicine

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: German Multicenter EPO Stroke Trial (Phase II/III)

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: neurological/functional outcome as measured by the Barthel Index (BI)

Secondary outcome:

modified Rankin Scale (mRS) responder

Barthel Index (BI)

mRS

NIH Stroke Scale

proportion of subjects with minimal disability (mRS 0-1)

all-cause mortality

mortality directly related to stroke

proportion of subjects with BI>=95

proportion of subjects with BI=100

proportion of subjects with neurological recovery

distribution of mRS scores

distribution of BI scores

distribution of NIH Stroke Scale scores

serum level of glial damage markers S100B and GFAP

lesion size (MRI DWI, flair)

overall survival

late recovery index (BI day 90 versus BI day 30)

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Neurologische Universitätsklinik der Georg-August-Universität Goettingen, Goettingen D-37075, Germany

Neurologische Klinik, Medizinische Hochschule Hannover, Hannover D-30625, Germany

Neurologische Klink, Klinikum Bremen-Mitte, Bremen D-28177, Germany

Neurologische Klinik, Allgemeines Krankenhaus Celle, Celle D-29223, Germany

Neurologische Klinik, Universität Erlangen-Nürnberg, Erlangen D-91054, Germany

Klinik und Poliklinik für Neurologie der Universität Leipzig, Leipzig D-04103, Germany

Klinik für Neurologie, Universität Essen, Essen D-45147, Germany

Klinik und Poliklinik für Neurologie, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden D-01307, Germany

Neurologische Klinik des Städtischen Klinikums Braunschweig, Braunschweig D-38126, Germany

homepage of the Max-Planck-Institute of Experimental Medicine

information about the German Multicenter EPO Stroke Study and previous related trials

Related publications:

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. Epub 2001 Mar 20.

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.

Lewczuk P, Hasselblatt M, Kamrowski-Kruck H, Heyer A, Unzicker C, Sirén AL, Ehrenreich H. Survival of hippocampal neurons in culture upon hypoxia: effect of erythropoietin. Neuroreport. 2000 Nov 9;11(16):3485-8.

Sirén AL, Knerlich F, Poser W, Gleiter CH, Brück W, Ehrenreich H. Erythropoietin and erythropoietin receptor in human ischemic/hypoxic brain. Acta Neuropathol. 2001 Mar;101(3):271-6.

Herrmann M, Ehrenreich H. Brain derived proteins as markers of acute stroke: their relation to pathophysiology, outcome prediction and neuroprotective drug monitoring. Restor Neurol Neurosci. 2003;21(3-4):177-90. Review.

Ehrenreich H, Hasselblatt M, Knerlich F, von Ahsen N, Jacob S, Sperling S, Woldt H, Vehmeyer K, Nave KA, Sirén AL. A hematopoietic growth factor, thrombopoietin, has a proapoptotic role in the brain. Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):862-7. Epub 2005 Jan 10.

Sirén AL, Radyushkin K, Boretius S, Kämmer 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. Epub 2005 Dec 9.

Ehrenreich H, Hinze-Selch D, Stawicki S, Aust C, Knolle-Veentjer S, Wilms S, Heinz G, Erdag S, Jahn H, Degner D, Ritzen M, Mohr A, Wagner M, Schneider U, Bohn M, Huber M, Czernik A, Pollmächer T, Maier W, Sirén AL, Klosterkötter J, Falkai P, Rüther E, Aldenhoff JB, Krampe H. Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin. Mol Psychiatry. 2007 Feb;12(2):206-20. Epub 2006 Oct 10.

Ehrenreich H, Fischer B, Norra C, Schellenberger F, Stender N, Stiefel M, Sirén 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. Epub 2007 Aug 29.

Starting date: January 2003
Ending date: June 2008
Last updated: April 1, 2008