• Jean-Louis Vincent, Christopher T Privalle, Mervyn Singer, José A Lorente, Erwin Boehm, Andreas Meier-Hellmann, Harald Darius, Ricard Ferrer, Josep-Maria Sirvent, Gernot Marx, and Joseph DeAngelo.
• 1Department of Intensive Care, Erasme Hospital, Université libre de Bruxelles, Brussels, Belgium. 2Apex Bioscience, Inc., Chapel Hill, NC. 3Bloomsbury Institute of Intensive Care Medicine, University College London, London, United Kingdom. 4CIBER Enfermedades Respiratorias, Getafe University Hospital, Universidad Europea, Madrid, Spain. 5Curacyte AG, Munich, Germany. 6Department of Anesthesiology, Intensive Care Medicine and Pain Management, HELIOS Klinikum Erfurt GmbH, Erfurt, Germany. 7Klinik fur Kardiologie, Angiologie and Konservative Intensivmedizin, Vivantes Klinikum Neukoelln, Berlin, Germany. 8Intensive Care Department, Hospital Universitari Mútua Terrassa, Terrassa, Barcelona, Spain. 9CIBER Enfermedades Respiratorias, Terrassa, Barcelona, Spain. 10Department of Intensive Care (ICU), Hospital Universitari Dr. Josep Trueta, Girona, Spain. 11Department of Intensive Care, RWTH University Hospital Aachen, Aachen, Germany.
• Crit. Care Med.. 2015 Jan 1;43(1):57-64.

ObjectiveTo compare the effectiveness and safety of the hemoglobin-based nitric oxide scavenger, pyridoxalated hemoglobin polyoxyethylene, against placebo in patients with vasopressor-dependent distributive shock.DesignMulticenter, randomized, placebo-controlled, open-label study.SettingSixty-one participating ICUs in six European countries (Austria, Belgium, Germany, the Netherlands, Spain, and United Kingdom).PatientsAll patients admitted with distributive shock, defined as the presence of at least two systemic inflammatory response syndrome criteria, persisting norepinephrine dependence and evidence of organ dysfunction/hypoperfusion despite adequate fluid resuscitation.InterventionsPatients were randomized to receive 0.25 mL/kg/hr pyridoxalated hemoglobin polyoxyethylene (20 mg Hb/kg/hr) or an equal volume of placebo, infused for up to 150 hours, in addition to conventional vasopressor therapy.Measurements And Main ResultsThe study was stopped after interim analysis showed higher mortality in the pyridoxalated hemoglobin polyoxyethylene group and an increased prevalence of adverse events. At this time, 377 patients had been randomized to pyridoxalated hemoglobin polyoxyethylene (n = 183) or placebo (n = 194). Age, gender, type of patient (medical/surgical), and Acute Physiology and Chronic Health Evaluation II scores were similar between groups. Twenty-eight-day mortality rate was 44.3% in the pyridoxalated hemoglobin polyoxyethylene group versus 37.6% in the placebo group (OR, 1.29; 95% CI, 0.85-1.95; p = 0.227). In patients with higher organ dysfunction scores (Sepsis-related Organ Failure Assessment > 13), mortality rates were significantly higher in the pyridoxalated hemoglobin polyoxyethylene group when compared with those in placebo-treated patients (60.9% vs 39.2%; p = 0.014). Survivors who received pyridoxalated hemoglobin polyoxyethylene had a longer vasopressor-free time (21.3 vs 19.7 d; p = 0.035).ConclusionsIn this randomized, controlled phase III trial in patients with vasopressor-dependent distributive shock, administration of a pyridoxalated hemoglobin solution decreased the need for vasopressors but was associated with a trend to increased mortality.

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