GR270773 In The Treatment Of Suspected Or Confirmed Gram-Negative Severe Sepsis In Adults
Condition: Sepsis
MeSH terms: Sepsis; Toxemia
Intervention: Intravenous GR270773- Phospholipid Emulsion; Placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Enrollment: 1415.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: severe sepsis; septic shock; Gram-negative infection; phospholipid emulsion

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.