A Prospective, Randomized, Double-blind, Placebo Controlled, Dose Ranging, Multi-Center Study of the Safety and Efficacy of Three Days Continuous Intravenous Infusion of GR270773 in the Treatment of Suspected or Confirmed Gram-negative Severe Sepsis in Adults

Date de début de l'étude : 1 septembre 2004

Inclusion criteria: * Receiving parenteral antibiotic therapy for a suspected or confirmed Gram-negative infection. * Have at least one new hypoperfusion abnormality or at least one new onset organ failure resulting from the current septic episode. * Must be available and able to receive the first dose of study medication no more than 12 hours after the confirmation of a new hypoperfusion abnormality or new onset organ failure and within 36 hours after the initiation of new parenteral antibacterial therapy for the suspected or confirmed Gram-negative infection believed to be responsible for this episode of sepsis. Exclusion criteria: * Subject is unlikely to remain in hospital for a minimum of three days (72 hours) following enrollment. * Subject has neutropenia (e.g., subject recently receiving cytotoxic chemotherapy with absolute neutrophil count \<500/mcL or expected to decline to \<500/mcL in the next 3 days). * Subject has known active hemolytic disease, immune hemolytic anemias, hemoglobinopathies (sickle cell anemia and thalassemia major). * Subject has a known bone marrow disorder of inadequate red cell production (eg, aplastic anemia, myelodysplasia). * Subject is at increased risk of complications from GR270773-related hemolysis due to the inability to increase cardiac function sufficiently to meet the demands for oxygen delivery. * Subject has a baseline hemoglobin (measured after adequate volume resuscitation) \<9.0 g/dL (5.59 mmol/L). * Subject is currently being treated with XIGRIS (Drotrecogin alfa (activated)) or its use is considered imminent (ie., a decision to treat with XIGRIS has been made). * Subject has a history of allergic reaction to eggs (or egg products), soybeans, INTRALIPID, or any component of GR270773. * Subject has been designated as 'not full support do not resuscitate' (DNR), or other equivalent status which prohibits the use of life supporting interventions (e.g., mechanical ventilation, dialysis/hemofiltration, or others) thereby limiting the treatment options available. Note: Subjects with advanced directives prohibiting only chest compression (CPR) are eligible for the study. * Subject has preexisting severe liver disease such as cirrhosis, primary biliary cirrhosis or known preexisting Child-Pugh class B or C liver dysfunction. * Subject is moribund (a state in which death is perceived to be imminent) or has a life expectancy of less than 3 months due to an underlying disease. * Subject is currently receiving one of the following prohibited concomitant medications; parenteral nutrition supplements containing lipid emulsions (e.g., INTRALIPID), amphotericin, liposomal amphotericin, or amphotericin B lipid complex.