Multicenter Efficacy Study of Recombinant Human Erythropoietin in Acute Ischemic Stroke

Stroke, Acute Clinical Trial

— ESS  

Official title:

German Multicenter EPO Stroke Trial (Phase II/III)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00604630
• Other study ID #: BfArM-4019639/2002
• Secondary ID: "EPO Stroke Stud
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: January 17, 2008
• Last updated: October 21, 2008
• Start date: January 2003
• Est. completion date: June 2008

Study information

• Verified date: September 2008
• Source: Max-Planck-Institute of Experimental Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 522
• Est. completion date: June 2008
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infarction, Middle Cerebral Artery
• Middle Cerebral Artery Stroke
• Stroke
• Stroke, Acute

Intervention

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
• 0.9% NaCl
50ml 0.9% NaCl iv on 3 consecutive days, starting within 6 hours after onset of symptoms

Locations

Country	Name	City	State
Germany	Neurologische Klinik des Städtischen Klinikums Braunschweig	Braunschweig
Germany	Neurologische Klink, Klinikum Bremen-Mitte	Bremen
Germany	Neurologische Klinik, Allgemeines Krankenhaus Celle	Celle
Germany	Klinik und Poliklinik für Neurologie, Universitätsklinikum Carl Gustav Carus der TU Dresden	Dresden
Germany	Neurologische Klinik, Universität Erlangen-Nürnberg	Erlangen
Germany	Klinik für Neurologie, Universität Essen	Essen
Germany	Neurologische Universitätsklinik der Georg-August-Universität Goettingen	Goettingen
Germany	Neurologische Klinik, Medizinische Hochschule Hannover	Hannover
Germany	Klinik und Poliklinik für Neurologie der Universität Leipzig	Leipzig

Sponsors (3)

Lead Sponsor	Collaborator
Max-Planck-Institute of Experimental Medicine	Johnson & Johnson, Parexel

Country where clinical trial is conducted

Germany, 

References & Publications (9)

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. — View 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, Rüther E, Kochen M, Gefeller O, Gleiter C, Wessel TC, De Ryck M, Itri L, Prange H, Cerami A, Brines M, Sirén AL. Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med. 2002 Aug;8(8):495-505. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Sirén 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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neurological/functional outcome as measured by the Barthel Index (BI)		day 90	No
Secondary	Modified Rankin Scale (mRS) responder		day 90	No
Secondary	Barthel Index (BI)		day 30	No
Secondary	mRS		day30, day 90	No
Secondary	NIH Stroke Scale		day 1, 3, 7, 30, 90	No
Secondary	Proportion of subjects with minimal disability (mRS 0-1)		day 30, day 90	No
Secondary	All-cause mortality		day 90	Yes
Secondary	Mortality directly related to stroke		day 90	Yes
Secondary	Proportion of subjects with BI >= 95		day 30, day 90	No
Secondary	Proportion of subjects with BI=100		day 30, day 90	No
Secondary	Proportion of subjects with neurological recovery		day 3, 7, 30, 90	No
Secondary	Distribution of mRS scores		day 30, day 90	No
Secondary	Distribution of BI scores		day 30, day 90	No
Secondary	Distribution of NIH Stroke Scale scores		day 30, day 90	No
Secondary	Serum level of glial damage markers S100B and GFAP		day 1, 2, 3, 4, 7	No
Secondary	Lesion size (MRI DWI, flair)		day 1, day 7	No
Secondary	Overall survival		day 90	Yes
Secondary	Late recovery index (BI day 90 versus BI day 30)		day 30 to day 90	No

External Links

•   homepage of the Max-Planck-Institute of Experimental Medicine
•   information about the German Multicenter EPO Stroke Study and previous related trials