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. - LIPOS
- Conditions
- Suspected or Confirmed Gram-negative Severe Sepsis in Adults
- Registration Number
- EUCTR2004-000406-51-ES
- Lead Sponsor
- GlaxoSmithkline, S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 0
? Subjects must have one of the following suspected or confirmed Gram-negative bacterial infections – Gram-negative bacteraemia, intra-abdominal infection, nosocomial pneumonia or pyelonephritis.
? Subjects must be receiving new parenteral antibacterial treatment for the suspected or confirmed Gram-negative infection believed to be responsible for this episode of sepsis. The subject must not receive more that 36 hours treatment with this new antibacterial agent prior to initiating treatment with study medication.
? Subject has signs of new-onset severe sepsis as evidenced by at least one of the following hypoperfusion abnormalities OR organ failures caused by the current episode of sepsis, persistent oligouria, metabolic acidosis, respiratory failure, cardiovascular failure or coagulopathy. Subject must receive study medication within 12 hours of confirmation of the first sepsis-related hypoperfusion abnormality or organ failure.
? Subject or their legally acceptable representative has provided written and dated informed consent to participate in the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1. Subject has neutropenia (e.g., subject recently receiving cytotoxic chemotherapy with absolute neutrophil count <500/?L or expected to decline to <500/?L in the next 3 days).
2. Subject is known or believed to suffer from hereditary spherocytosis or S.E. Asian elliptocytosis.
3. Subject has known active hemolytic disease; immune hemolytic anemias, hemoglobinopathies (sickle cell anemia and thalassemia major).
4. Subject has a known bone marrow disorder of inadequate red cell production (eg, aplastic anemia, myelodysplasia).
5. Subject is at increased risk of complications from GR270773 Emulsion-related hemolysis due to the inability to increase cardiac function sufficiently to meet the demands for oxygen delivery.
6. Subject has a baseline hemoglobin (measured after adequate volume resuscitation) <9.0 g/dL (5.59 mmol/L).
7. 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).
8. 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.
9. Subject has preexisting severe liver disease such as cirrhosis, primary biliary cirrhosis or known preexisting Child-Pugh class B or C liver dysfunction.
10. 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of this study is to estimate the size of the GR270773 Emulsion treatment effect on 28-day all-cause mortality for two doses of GR270773 Emulsion versus placebo in adult subjects with suspected or confirmed Gram-negative severe sepsis. ;Secondary Objective: The secondary objectives are:<br>a) To evaluate the impact of treatment with GR270773 Emulsion on morbidity, measured as the proportion of subjects experiencing new onset organ failure, regardless of cause, versus placebo.<br>b) To compare the safety and tolerability of two doses of GR270773 Emulsion versus placebo. <br>;Primary end point(s): The primary endpoint is the all-cause mortality rate at Day 28.
- Secondary Outcome Measures
Name Time Method