GR270773 In The Treatment Of Suspected Or Confirmed Gram-Negative Severe Sepsis In Adults

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 2

Conditions: Sepsis

Treatments: Other: Placebo; Drug: Intravenous GR270773- Phospholipid Emulsion

Study type: Interventional

Funder types: Industry

Identifiers

NCT00089986

EMD20001

Details and patient eligibility

About

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.

Enrollment: 1,415 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.