Recombinant human erythropoietin in the treatment of acute ischemic stroke - PubMed (original) (raw)
Randomized Controlled Trial
. 2009 Dec;40(12):e647-56.
doi: 10.1161/STROKEAHA.109.564872. Epub 2009 Oct 15.
Karin Weissenborn, Hilmar Prange, Dietmar Schneider, Christian Weimar, Katja Wartenberg, Peter D Schellinger, Matthias Bohn, Harald Becker, Martin Wegrzyn, Peter Jähnig, Manfred Herrmann, Michael Knauth, Mathias Bähr, Wolfgang Heide, Armin Wagner, Stefan Schwab, Heinz Reichmann, Günther Schwendemann, Reinhard Dengler, Andreas Kastrup, Claudia Bartels; EPO Stroke Trial Group
Collaborators, Affiliations
- PMID: 19834012
- DOI: 10.1161/STROKEAHA.109.564872
Randomized Controlled Trial
Recombinant human erythropoietin in the treatment of acute ischemic stroke
Hannelore Ehrenreich et al. Stroke. 2009 Dec.
Abstract
Background and purpose: Numerous preclinical findings and a clinical pilot study suggest that recombinant human erythropoietin (EPO) provides neuroprotection that may be beneficial for the treatment of patients with ischemic stroke. Although EPO has been considered to be a safe and well-tolerated drug over 2 decades, recent studies have identified increased thromboembolic complications and/or mortality risks on EPO administration to patients with cancer or chronic kidney disease. Accordingly, the double-blind, placebo-controlled, randomized German Multicenter EPO Stroke Trial (Phase II/III; ClinicalTrials.gov Identifier: NCT00604630) was designed to evaluate efficacy and safety of EPO in stroke.
Methods: This clinical trial enrolled 522 patients with acute ischemic stroke in the middle cerebral artery territory (intent-to-treat population) with 460 patients treated as planned (per-protocol population). Within 6 hours of symptom onset, at 24 and 48 hours, EPO was infused intravenously (40,000 IU each). Systemic thrombolysis with recombinant tissue plasminogen activator was allowed and stratified for.
Results: Unexpectedly, a very high number of patients received recombinant tissue plasminogen activator (63.4%). On analysis of total intent-to-treat and per-protocol populations, neither primary outcome Barthel Index on Day 90 (P=0.45) nor any of the other outcome parameters showed favorable effects of EPO. There was an overall death rate of 16.4% (n=42 of 256) in the EPO and 9.0% (n=24 of 266) in the placebo group (OR, 1.98; 95% CI, 1.16 to 3.38; P=0.01) without any particular mechanism of death unexpected after stroke.
Conclusions: Based on analysis of total intent-to-treat and per-protocol populations only, this is a negative trial that also raises safety concerns, particularly in patients receiving systemic thrombolysis.
Comment in
- Back to the ground.
Dame C. Dame C. Stroke. 2010 Mar;41(3):e166; author reply 167-8. doi: 10.1161/STROKEAHA.109.575274. Epub 2010 Feb 4. Stroke. 2010. PMID: 20133914 No abstract available. - Neurovascular protection by erythropoietin: from the bedside back to the bench.
Tufekci KU, Genc K. Tufekci KU, et al. Stroke. 2010 Jul;41(7):e462. doi: 10.1161/STROKEAHA.110.585968. Epub 2010 May 13. Stroke. 2010. PMID: 20466988 No abstract available. - Safety concerns with the clinical use of erythropoietin in acute ischemic stroke.
Kumral A, Genc S, Kutluk K, Ozkan H. Kumral A, et al. Stroke. 2010 Jul;41(7):e469. doi: 10.1161/STROKEAHA.110.585943. Epub 2010 May 13. Stroke. 2010. PMID: 20466989 No abstract available.
Similar articles
- Asymmetric dimethylarginine in response to recombinant tissue-type plasminogen activator and erythropoietin in acute stroke.
Worthmann H, Martens-Lobenhoffer J, Joumaah M, Li N, Lichtinghagen R, Hecker H, Kielstein JT, Ehrenreich H, Bode-Böger SM, Weissenborn K. Worthmann H, et al. Stroke. 2013 Aug;44(8):2128-33. doi: 10.1161/STROKEAHA.113.001145. Epub 2013 Jun 20. Stroke. 2013. PMID: 23788583 Clinical Trial. - Erythropoietin improves long-term neurological outcome in acute ischemic stroke patients: a randomized, prospective, placebo-controlled clinical trial.
Tsai TH, Lu CH, Wallace CG, Chang WN, Chen SF, Huang CR, Tsai NW, Lan MY, Sung PH, Liu CF, Yip HK. Tsai TH, et al. Crit Care. 2015 Feb 25;19(1):49. doi: 10.1186/s13054-015-0761-8. Crit Care. 2015. PMID: 25888250 Free PMC article. Clinical Trial. - Erythropoietin molecules to treat acute ischemic stroke: a translational dilemma!
Lapchak PA. Lapchak PA. Expert Opin Investig Drugs. 2010 Oct;19(10):1179-86. doi: 10.1517/13543784.2010.517954. Expert Opin Investig Drugs. 2010. PMID: 20828227 Free PMC article. Review. - Erythropoietin Treatment in Patients with Acute Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Yao X, Wang D, Li H, Shen H, Shu Z, Chen G. Yao X, et al. Curr Drug Deliv. 2017 Sep 6;14(6):853-860. doi: 10.2174/1567201813666160822104813. Curr Drug Deliv. 2017. PMID: 27549753 Review.
Cited by
- Early Postnatal Administration of Erythropoietin and Its Association with Neurodevelopmental Outcomes and Incidence of Intraventricular Hemorrhage and Hypoxic-Ischemic Encephalopathy: A Four-Week Observational Study.
Costescu OC, Manea AM, Boia ER, Cioboata DM, Doandes FM, Enatescu I, Costescu S, Prodan M, Boia M. Costescu OC, et al. Pediatr Rep. 2024 Apr 28;16(2):339-352. doi: 10.3390/pediatric16020030. Pediatr Rep. 2024. PMID: 38804373 Free PMC article. - Neuronal nitric oxide synthase required for erythropoietin modulation of heart function in mice.
Lee J, Rogers HM, Springer DA, Noguchi CT. Lee J, et al. Front Physiol. 2024 Apr 2;15:1338476. doi: 10.3389/fphys.2024.1338476. eCollection 2024. Front Physiol. 2024. PMID: 38628440 Free PMC article. - Erythropoietin-derived peptide ARA290 mediates brain tissue protection through the β-common receptor in mice with cerebral ischemic stroke.
Wang RL, Yang ZH, Huang YY, Hu Y, Wang YL, Yan F, Zheng YM, Han ZP, Fan JF, Tao Z, Zhao HP, Li SJ, Luo YM. Wang RL, et al. CNS Neurosci Ther. 2024 Mar;30(3):e14676. doi: 10.1111/cns.14676. CNS Neurosci Ther. 2024. PMID: 38488446 Free PMC article. - Identifying applications of virtual reality to benefit the stroke translational pipeline.
Bone M, Malik M, Crilly S. Bone M, et al. Brain Neurosci Adv. 2023 Jun 21;7:23982128231182506. doi: 10.1177/23982128231182506. eCollection 2023 Jan-Dec. Brain Neurosci Adv. 2023. PMID: 37360628 Free PMC article. Review. - The cytokine receptor CRLF3 is a human neuroprotective EV-3 (Epo) receptor.
Knorr DY, Rodriguez Polo I, Pies HS, Schwedhelm-Domeyer N, Pauls S, Behr R, Heinrich R. Knorr DY, et al. Front Mol Neurosci. 2023 Apr 6;16:1154509. doi: 10.3389/fnmol.2023.1154509. eCollection 2023. Front Mol Neurosci. 2023. PMID: 37168680 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials