NCT00604630

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
522

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jan 2003

Longer than P75 for phase_2

Geographic Reach
1 country

9 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2003

Completed
5 years until next milestone

First Submitted

Initial submission to the registry

January 17, 2008

Completed
13 days until next milestone

First Posted

Study publicly available on registry

January 30, 2008

Completed
4 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2008

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2008

Completed
Last Updated

October 22, 2008

Status Verified

September 1, 2008

Enrollment Period

5.4 years

First QC Date

January 17, 2008

Last Update Submit

October 21, 2008

Conditions

Infarction, Middle Cerebral ArteryMiddle Cerebral Artery StrokeStroke, Acute

Keywords

strokeEPOerythropoietinischemiahypoxiaantiapoptosisneuroprotectionrtPAthrombolysisstroke, middle cerebral arteryIschemic stroke in the middle cerebral artery territory

Outcome Measures

Primary Outcomes (1)

  • Neurological/functional outcome as measured by the Barthel Index (BI)

    day 90

Secondary Outcomes (17)

  • Modified Rankin Scale (mRS) responder

    day 90

  • Barthel Index (BI)

    day 30

  • mRS

    day30, day 90

  • NIH Stroke Scale

    day 1, 3, 7, 30, 90

  • Proportion of subjects with minimal disability (mRS 0-1)

    day 30, day 90

  • +12 more secondary outcomes

Study Arms (2)

placebo

PLACEBO COMPARATOR

50ml 0.9% NaCL

Drug: 0.9% NaCl

verum

ACTIVE COMPARATOR

erythropoietin alfa 40,000 IU iv in 50ml 0.9% NaCl

Drug: recombinant human erythropoietin alfa

Interventions

recombinant human erythropoietin alfaDRUG

40,000 IU in 50ml 0.9% NaCl iv on 3 consecutive days, starting within 6 hours after onset of symptoms

Also known as: ERYPO
verum
0.9% NaClDRUG

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

placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

Neurologische Klinik des Städtischen Klinikums Braunschweig

Braunschweig, D-38126, Germany

Location

Neurologische Klink, Klinikum Bremen-Mitte

Bremen, D-28177, Germany

Location

Neurologische Klinik, Allgemeines Krankenhaus Celle

Celle, D-29223, Germany

Location

Klinik und Poliklinik für Neurologie, Universitätsklinikum Carl Gustav Carus der TU Dresden

Dresden, D-01307, Germany

Location

Neurologische Klinik, Universität Erlangen-Nürnberg

Erlangen, D-91054, Germany

Location

Klinik für Neurologie, Universität Essen

Essen, D-45147, Germany

Location

Neurologische Universitätsklinik der Georg-August-Universität Goettingen

Göttingen, D-37075, Germany

Location

Neurologische Klinik, Medizinische Hochschule Hannover

Hanover, D-30625, Germany

Location

Klinik und Poliklinik für Neurologie der Universität Leipzig

Leipzig, D-04103, Germany

Location

Related Publications (11)

  • 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.

    PMID: 11259643BACKGROUND

  • 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.

    PMID: 12435860BACKGROUND

  • Lewczuk P, Hasselblatt M, Kamrowski-Kruck H, Heyer A, Unzicker C, Siren AL, Ehrenreich H. Survival of hippocampal neurons in culture upon hypoxia: effect of erythropoietin. Neuroreport. 2000 Nov 9;11(16):3485-8. doi: 10.1097/00001756-200011090-00017.

    PMID: 11095504BACKGROUND

  • Siren AL, Knerlich F, Poser W, Gleiter CH, Bruck W, Ehrenreich H. Erythropoietin and erythropoietin receptor in human ischemic/hypoxic brain. Acta Neuropathol. 2001 Mar;101(3):271-6. doi: 10.1007/s004010000297.

    PMID: 11307627BACKGROUND

  • 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.

    PMID: 14530580BACKGROUND

  • Ehrenreich H, Hasselblatt M, Knerlich F, von Ahsen N, Jacob S, Sperling S, Woldt H, Vehmeyer K, Nave KA, Siren 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. doi: 10.1073/pnas.0406008102. Epub 2005 Jan 10.

    PMID: 15642952BACKGROUND

  • 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.

    PMID: 16339796BACKGROUND

  • 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, Pollmacher T, Maier W, Siren AL, Klosterkotter J, Falkai P, Ruther 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. doi: 10.1038/sj.mp.4001907. Epub 2006 Oct 10.

    PMID: 17033631BACKGROUND

  • 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.

    PMID: 17728357BACKGROUND

  • 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.

    PMID: 21852153DERIVED

  • Ehrenreich H, Weissenborn K, Prange H, Schneider D, Weimar C, Wartenberg K, Schellinger PD, Bohn M, Becker H, Wegrzyn M, Jahnig P, Herrmann M, Knauth M, Bahr 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. doi: 10.1161/STROKEAHA.109.564872. Epub 2009 Oct 15.

    PMID: 19834012DERIVED

Related Links

MeSH Terms

Conditions

Infarction, Middle Cerebral ArteryStrokeIschemiaHypoxia

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Cerebral InfarctionBrain InfarctionBrain IschemiaCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesCerebral Arterial DiseasesIntracranial Arterial DiseasesVascular DiseasesCardiovascular DiseasesInfarctionPathologic ProcessesPathological Conditions, Signs and SymptomsNecrosisSigns and Symptoms, RespiratorySigns and Symptoms

Intervention Hierarchy (Ancestors)

Crystalloid SolutionsIsotonic SolutionsSolutionsPharmaceutical Preparations

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

January 17, 2008

First Posted

January 30, 2008

Study Start

January 1, 2003

Primary Completion

June 1, 2008

Study Completion

June 1, 2008

Last Updated

October 22, 2008

Record last verified: 2008-09

Locations

DE(9)