Multicenter Efficacy Study of Recombinant Human Erythropoietin in Acute Ischemic Stroke (ESS)

This study has been completed.

Sponsor:

Collaborators:

Johnson & Johnson

Parexel

Information provided by:

Max-Planck-Institute of Experimental Medicine

ClinicalTrials.gov Identifier:

NCT00604630

First received: January 17, 2008

Last updated: October 21, 2008

Last verified: September 2008

History of Changes

Tracking Information
First Received Date ^ICMJE	January 17, 2008
Last Updated Date	October 21, 2008
Start Date ^ICMJE	January 2003
Primary Completion Date	June 2008 (final data collection date for primary outcome measure)
Current Primary Outcome Measures ^ICMJE (submitted: January 29, 2008)	Neurological/functional outcome as measured by the Barthel Index (BI) [ Time Frame: day 90 ] [ Designated as safety issue: No ]
Original Primary Outcome Measures ^ICMJE	Same as current
Change History	Complete list of historical versions of study NCT00604630 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ^ICMJE (submitted: October 16, 2008)	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 ]
Original Secondary Outcome Measures ^ICMJE (submitted: January 29, 2008)	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 ]
Current Other Outcome Measures ^ICMJE	Not Provided
Original Other Outcome Measures ^ICMJE	Not Provided

Descriptive Information
Brief Title ^ICMJE	Multicenter Efficacy Study of Recombinant Human Erythropoietin in Acute Ischemic Stroke
Official Title ^ICMJE	German Multicenter EPO Stroke Trial (Phase II/III)
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.
Detailed Description	Not Provided
Study Type ^ICMJE	Interventional
Study Phase	Phase 2 Phase 3
Study Design ^ICMJE	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Condition ^ICMJE	Infarction, Middle Cerebral Artery Middle Cerebral Artery Stroke Stroke, Acute
Intervention ^ICMJE	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 Other Name: ERYPO Drug: 0.9% NaCl 50ml 0.9% NaCl iv on 3 consecutive days, starting within 6 hours after onset of symptoms
Study Arm (s)	Placebo Comparator: placebo 50ml 0.9% NaCL Intervention: Drug: 0.9% NaCl Active Comparator: verum erythropoietin alfa 40,000 IU iv in 50ml 0.9% NaCl Intervention: Drug: recombinant human erythropoietin alfa
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. 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. Ehrenreich H, Weissenborn K, Prange H, Schneider D, Weimar C, Wartenberg K, Schellinger PD, Bohn M, Becker H, Wegrzyn M, Jähnig P, Herrmann M, Knauth M, Bähr M, Heide W, Wagner A, Schwab S, Reichmann H, Schwendemann G, Dengler R, Kastrup A, Bartels C; EPO Stroke Trial Group. Recombinant human erythropoietin in the treatment of acute ischemic stroke. Stroke. 2009 Dec;40(12):e647-56. Epub 2009 Oct 15.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information
Recruitment Status ^ICMJE	Completed
Enrollment ^ICMJE	522
Completion Date	June 2008
Primary Completion Date	June 2008 (final data collection date for primary outcome measure)
Eligibility Criteria ^ICMJE	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
Gender	Both
Ages	18 Years and older
Accepts Healthy Volunteers	No
Contacts ^ICMJE	Contact information is only displayed when the study is recruiting subjects
Location Countries ^ICMJE	Germany

Administrative Information
NCT Number ^ICMJE	NCT00604630
Other Study ID Numbers ^ICMJE	BfArM-4019639/2002, "EPO Stroke Study", "Ehrenreich EPO Stroke Study", "Ehrenreich Study"
Has Data Monitoring Committee	Yes
Responsible Party	Prof. Dr. Dr. Hannelore Ehrenreich (MD, DVM), Head of the Division of Clinical Neuroscience, Max-Planck-Institute of Experimental Medicine
Study Sponsor ^ICMJE	Max-Planck-Institute of Experimental Medicine
Collaborators ^ICMJE	Johnson & Johnson Parexel
Investigators ^ICMJE	Not Provided
Information Provided By	Max-Planck-Institute of Experimental Medicine
Verification Date	September 2008
^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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