E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | Suspected or Confirmed Gram-negative Severe Sepsis in Adults | |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial | 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. | |
E.2.2 | Secondary objectives of the trial | The secondary objectives are: 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. b) To compare the safety and tolerability of two doses of GR270773 Emulsion versus placebo. | |
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria | 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. | |
E.4 | Principal exclusion criteria | 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. | |
E.5 End points |
E.5.1 | Primary end point(s) | The primary endpoint is the all-cause mortality rate at Day 28. | |
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 | The trial involves single site in the Member State concerned | No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |