Multicenter Efficacy Study of Recombinant Human Erythropoietin in Acute Ischemic Stroke - Full Text View

Sponsors and Collaborators:	Max-Planck-Institute of Experimental Medicine Johnson & Johnson Parexel
Information provided by:	Max-Planck-Institute of Experimental Medicine
ClinicalTrials.gov Identifier:	NCT00604630

Purpose

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.

Condition	Intervention	Phase
Infarction, Middle Cerebral Artery Middle Cerebral Artery Stroke Stroke, Acute	Drug: recombinant human erythropoietin alfa Drug: 0.9% NaCl	Phase II Phase III

Drug Information available for: Epoetin alfa Erythropoietin Alteplase Tissue-type plasminogen activator

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	German Multicenter EPO Stroke Trial (Phase II/III)

Further study details as provided by Max-Planck-Institute of Experimental Medicine:

Primary Outcome Measures:

Neurological/functional outcome as measured by the Barthel Index (BI) [ Time Frame: day 90 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Modified Rankin Scale (mRS) responder [ Time Frame: day 90 ] [ Designated as safety issue: No ]
Barthel Index (BI) [ Time Frame: day 30 ] [ Designated as safety issue: No ]
mRS [ Time Frame: day30, day 90 ] [ Designated as safety issue: No ]
NIH Stroke Scale [ Time Frame: day 1, 3, 7, 30, 90 ] [ Designated as safety issue: No ]
Proportion of subjects with minimal disability (mRS 0-1) [ Time Frame: day 30, day 90 ] [ Designated as safety issue: No ]
All-cause mortality [ Time Frame: day 90 ] [ Designated as safety issue: Yes ]
Mortality directly related to stroke [ Time Frame: day 90 ] [ Designated as safety issue: Yes ]
Proportion of subjects with BI >= 95 [ Time Frame: day 30, day 90 ] [ Designated as safety issue: No ]
Proportion of subjects with BI=100 [ Time Frame: day 30, day 90 ] [ Designated as safety issue: No ]
Proportion of subjects with neurological recovery [ Time Frame: day 3, 7, 30, 90 ] [ Designated as safety issue: No ]
Distribution of mRS scores [ Time Frame: day 30, day 90 ] [ Designated as safety issue: No ]
Distribution of BI scores [ Time Frame: day 30, day 90 ] [ Designated as safety issue: No ]
Distribution of NIH Stroke Scale scores [ Time Frame: day 30, day 90 ] [ Designated as safety issue: No ]
Serum level of glial damage markers S100B and GFAP [ Time Frame: day 1, 2, 3, 4, 7 ] [ Designated as safety issue: No ]
Lesion size (MRI DWI, flair) [ Time Frame: day 1, day 7 ] [ Designated as safety issue: No ]
Overall survival [ Time Frame: day 90 ] [ Designated as safety issue: Yes ]
Late recovery index (BI day 90 versus BI day 30) [ Time Frame: day 30 to day 90 ] [ Designated as safety issue: No ]

Enrollment:	522
Study Start Date:	January 2003
Study Completion Date:	June 2008
Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
placebo: Placebo Comparator 50ml 0.9% NaCL	Drug: 0.9% NaCl 50ml 0.9% NaCl iv on 3 consecutive days, starting within 6 hours after onset of symptoms
verum: Active Comparator erythropoietin alfa 40,000 IU iv in 50ml 0.9% NaCl	Drug: recombinant human erythropoietin alfa 40,000 IU in 50ml 0.9% NaCl iv on 3 consecutive days, starting within 6 hours after onset of symptoms

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00604630

Locations

Germany
Neurologische Universitätsklinik der Georg-August-Universität Goettingen
Goettingen, Germany, D-37075
Neurologische Klinik, Medizinische Hochschule Hannover
Hannover, Germany, D-30625
Neurologische Klink, Klinikum Bremen-Mitte
Bremen, Germany, D-28177
Neurologische Klinik, Allgemeines Krankenhaus Celle
Celle, Germany, D-29223
Neurologische Klinik des Städtischen Klinikums Braunschweig
Braunschweig, Germany, D-38126
Klinik und Poliklinik für Neurologie der Universität Leipzig
Leipzig, Germany, D-04103
Klinik für Neurologie, Universität Essen
Essen, Germany, D-45147
Klinik und Poliklinik für Neurologie, Universitätsklinikum Carl Gustav Carus der TU Dresden
Dresden, Germany, D-01307
Neurologische Klinik, Universität Erlangen-Nürnberg
Erlangen, Germany, D-91054

Sponsors and Collaborators

Max-Planck-Institute of Experimental Medicine

Johnson & Johnson

Parexel

More Information

homepage of the Max-Planck-Institute of Experimental Medicine This link exits the ClinicalTrials.gov site

information about the German Multicenter EPO Stroke Study and previous related trials This link exits the ClinicalTrials.gov site

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.

Responsible Party:	Max-Planck-Institute of Experimental Medicine ( Prof. Dr. Dr. Hannelore Ehrenreich (MD, DVM), Head of the Division of Clinical Neuroscience )
Study ID Numbers:	BfArM-4019639/2002, "EPO Stroke Study", "Ehrenreich EPO Stroke Study", "Ehrenreich Study"
Study First Received:	January 17, 2008
Last Updated:	October 21, 2008
ClinicalTrials.gov Identifier:	NCT00604630
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Max-Planck-Institute of Experimental Medicine:

stroke
EPO
erythropoietin
ischemia
hypoxia
antiapoptosis

neuroprotection
rtPA
thrombolysis
stroke, middle cerebral artery
Ischemic stroke in the middle cerebral artery territory

Study placed in the following topic categories:

Epoetin Alfa
Cerebral Infarction
Stroke
Vascular Diseases
Tissue Plasminogen Activator
Central Nervous System Diseases
Ischemia
Cerebral Arterial Diseases

Brain Diseases
Intracranial Arterial Diseases
Cerebrovascular Disorders
Necrosis
Infarction, Middle Cerebral Artery
Brain Ischemia
Brain Infarction
Infarction

Additional relevant MeSH terms:

Pathologic Processes
Hematinics
Therapeutic Uses
Hematologic Agents

Nervous System Diseases
Cardiovascular Diseases
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009