• Hannelore Ehrenreich, 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, and EPO Stroke Trial Group.
• Division of Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany. ehrenreich@em.mpg.de
• Stroke. 2009 Dec 1; 40 (12): e647-56.

Background And PurposeNumerous 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.MethodsThis 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.ResultsUnexpectedly, 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.ConclusionsBased 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.

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