gr270773 in the treatment of suspected or confirmed gram-negative severe sepsis in adults

Conditions: Sepsis

Summary: the primary objective is to estimate the size of the gr270773 treatment effect on 28-day all-cause mortality for two doses of gr270773 versus placebo in adult subjects with suspected or confirmed gram-negative severe sepsis. gr270773 will be administered as a three-day continuous intravenous infusion.


Eligibility criteria:
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.

Keywords: severe sepsis septic shock gram-negative infection phospholipid emulsion