severe sepsis MedDRA version: 8.1 Level: LLT Classification code 10040047 Term: Sepsis
Conditions
Interventions
Trade Name: Xigris 20 mg
Product Name: Xigris 20 mg powder for solution for infusion
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: drotrecogin alfa (activated)
CAS Number:
Sponsors
Eli Lilly & Company Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Adult patients (>=18 years old) with severe sepsis and multiple organ dysfunction Patients with severe sepsis are defined by the following criteria. Both criteria must be met for a diagnosis of severe sepsis with multiple organ dysfunction. Presence of a suspected or proven infection. Patients with a suspected infection must have evidence of an infection, such as white blood cells in a normally sterile body fluid, perforated viscus, chest x-ray consistent with pneumonia and associated with purulent sputum production, or a clinical syndrome associated with a high probability of infection, for example, purpura fulminans or ascending cholangitis. Presence of multiple organ dysfunction, which is defined as two or more sepsis-associated organ dysfunctions defined below. Note: A patient must have organ dysfunctions attributable to the sepsis episode. The organ dysfunctions must be newly developed and not explained by underlying disease processes or by the effects of concomitant therapy. A non-sepsis-induced organ dysfunction may not be used to qualify the patient for the study even if the organ dysfunction worsens as a result of the sepsis episode. Cardiovascular: An arterial systolic blood pressure (SBP) of =90 mm Hg or MAP >=70 mm Hg. Adequate fluid resuscitation or adequate intravascular volume is defined as one or more of the following: (a) the administration of an intravenous fluid bolus (>=500 mL of crystalloid solution, >=20 g of albumin, or >=200 mL of other colloid administered over 30 minutes or less); (b) pulmonary arterial wedge pressure >=12 mm Hg; or (c) central venous pressure >=8 mm Hg. Vasopressors are defined as the following: (a) dopamine >=5 g/kg/min or (b) norepinephrine, epinephrine, phenylephrine, or vasopressin at any dose. Dobutamine or dopexamine are not considered vasopressors. Renal: Average output 2 times the upper limit of the normal reference range for the institution prior to the onset of sepsis), the patient must meet two of the other four organ dysfunction criteria. Respiratory: Evidence of acute pulmonary dysfunction: PaO2/FiO2 =5.0 mEq/L AND (2) a plasma lactate level >1.5 times the upper limit of normal for the reporting laboratory. 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
Exclusion criteria
Exclusion criteria: Have documented multiple organ dysfunction for greater than 24 hours prior to the start of study drug or the first documented sepsis-induced organ dysfunction occurred greater than 36 hours prior to the start of study drug. Weigh less than 30 kg or greater than 135 kg. Have a platelet count 15,000 units/day within 8 hours of study entry or low molecular weight heparin used at any dose higher or more frequent than the recommended dose in the product label for prophylaxis within 12 hours of study entry. Warfarin, if used within 7 days of study entry or warfarin-type medications within 650 mg/day or compounds that contain ASA >650 mg/day within 3 days prior to study entry. Thrombolytic therapy (unless used to treat an intra-catheter thrombosis; however, care should be taken to avoid systemic administration) if used within 3 days of study enrollment (for example, streptokinase, tPA, rPA, and urokinase). Glycoprotein IIb/IIIa receptor antagonists within 7 days of study entry. Antithrombin infusion of >10,000 units within 12 hours of study entry. Protein C concentrate infusion within 24 hours of study entry. (Other anticoagulants, such as direct thrombin inhibitors (for example, hirudin, argatroban, bivalirudin, desirudin, lepirudin, ximelegatran, or melegatran) and factor Xa inhibitors (for example, fondaparinux) and o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to demonstrate that, in patients with protein C levels less than the lower limit of normal, alternative therapy will result in a greater increase in protein C level from Study Day 1 to Study Day 7 compared with patients receiving standard therapy with drotrecogin alfa (activated).;Secondary Objective: To assess the safety of higher doses and longer infusion durations of drotrecogin alfa (activated). To investigate if compared with patients on standard therapy: Patients with severe protein C deficiency and patients with moderate protein C deficiency, a higher dose/variable duration of therapy gives greater increase in protein C level from Day 1 to 7 Patients on alternative therapy who complete infusion before Day 4, if protein C levels are not significantly different. If alternative therapy is associated with a decrease in 28 day all-cause and in-hospital mortality If alternative therapy is associated with improvements in organ dysfunction. If protein C level greater than the lower limit of normal is associated with lower 28 day all-cause mortality compared with a protein C level less than the lower limit of normal irrespective of treatment. PK/PD relationship between plasma APC, protein C levels, serious bleeding events, and mortality. ;Primary end point(s): The primary efficacy measure is mean change in protein C level from Study Day 1 to Study Day 7. Twenty-eight-day all-cause mortality. The 28-day time point is defined as 672 hours from the start of the drotrecogin alfa (activated) infusion. For non-drug-interventional patients, the 28-day time point is defined as 672 hours from the end of the pretreatment period. In-hospital mortality. Patients who remain hospitalized in the study hospital at Study Day 90 will be classified as “discharged alive.” Sequential Organ Failure Assessment (SOFA) scoring system will be used to assess organ function. SOFA scores are based on local laboratory data, vasopressor dosages, and | — |
Countries
Finland, France, Germany, Italy, Spain, Sweden, United Kingdom
Outcome results
None listed