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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 (Pϭ0.45) nor any of the other outcome parameters showed favorable effects of EPO. There was an overall death rate of 16.4% (nϭ42 of 256) in the EPO and 9.0% (nϭ24 of 266) in the placebo group (OR, 1.98; 95% CI, 1.16 to 3.38; Pϭ0.01) 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. (Stroke. 2009;40:e647-e656.)

Objective To evaluate the effect of different treatment strategies on enterohaemorrhagic Escherichia coli O104:H4 induced haemolytic uraemic syndrome.Design Multicentre retrospective case-control study.Setting 23 hospitals in northern Germany.Participants 298 adults with enterohaemorrhagic E coli induced haemolytic uraemic syndrome.Main outcome measures Dialysis, seizures, mechanical ventilation, abdominal surgery owing to perforation of the bowel or bowel necrosis, and death.Results 160 of the 298 patients (54%) temporarily required dialysis, with only three needing treatment long term. 37 patients (12%) had seizures, 54 (18%) required mechanical ventilation, and 12 (4%) died. No clear benefit was found from use of plasmapheresis or plasmapheresis with glucocorticoids. 67 of the patients were treated with eculizumab, a monoclonal antibody directed against the complement cascade. No short term benefit was detected that could be attributed to this treatment. 52 patients in one centre that used a strategy of aggressive treatment with combined antibiotics had fewer seizures (2% v 15%, P=0.03), fewer deaths (0% v 5%, p=0.029), required no abdominal surgery, and excreted E coli for a shorter duration.Conclusions Enterohaemorrhagic E coli induced haemolytic uraemic syndrome is a severe self limiting acute condition. Our findings question the benefit of eculizumab and of plasmapheresis with or without glucocorticoids. Patients with established haemolytic uraemic syndrome seemed to benefit from antibiotic treatment and this should be investigated in a controlled trial.

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