in severe sepsis patients with persistent vasopressordependent hypotension
Conditions
Interventions
Product Name: XIGRIS
Product Code: LY203638
Pharmaceutical Form: Powder for injection
INN or Proposed INN: Drotrecogina Alfa Activada
CAS Number: 98530-76-8
Current Sponsor code: Xigris
Other descript
Sponsors
Lilly S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: [1] Are adult (?18 year old) with severe sepsis that have been treated with at least 84 hours of a planned 96-hour infusion of commercial drotrecogin alfa (activated) under the applicable label in the investigative site country. [2] Continues to require vasopressor support (epinephrine, phenylephrine, vasopressin, or norepinephrine) at any dose or dopamine ?5?g/kg/min at the completion of at least 84 hours of a planned 96-hour infusion of therapy with commercial drotrecogin alfa (activated). 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 135 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 135
Exclusion criteria
Exclusion criteria: [3] Expected to require extensive and/or multiple surgical procedure(s) (i.e. staging surgery for burn patients) within the next 3 days. [4] Patients with a platelet count <30,000/mm3. [5] Are receiving therapeutic heparin, defined as ?15,000 IU per day. Unfractionated heparin up to 15 U/kg/hr may be used in conjunction with acute hemodialysis or continuous renal replacement therapy. [6] Are not expected to survive the 24 day (maximum) Study Treatment and Post Study Treatment Period given their preexisting uncorrectable medical condition. [7] Are moribund and death is perceived to be imminent within 24 hours. [8] Patients whose family and/or primary physician have not committed to aggressive management of the patient. For instance patients or patients? authorized representative is unwilling to allow red blood cell transfusions or an advanced directive to withhold life-sustaining treatment, with the exception of cardiopulmonary resuscitation (CPR), is present. [9] Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. [10] Are pregnant or are lactating and the milk is to be ingested by the child. [11] Are contraindicated for treatment with drotrecogin alfa (activated) under the applicable label in the investigative site country. [12] Have no completed written informed consent signed by the patient or the patient?s legal representative. [13] No longer dependent upon vasopressors
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate, in severe sepsis patients with persistent vasopressordependent hypotension at the end of a 96-hour infusion of commercial drotrecogin alfa (activated), whether continued administration of drotrecogin alfa (activated) for up to 72 additional hours results in more rapid resolution of vasopressor-dependent hypotension versus placebo.;Secondary Objective: To evaluate if extended treatment with drotrecogin alfa (activated) compared with placebo reduces 28-day* all cause mortality (i.e., mortality assessed 28-days from the start of commercial drug therapy) and in hospital mortality. ? To evaluate the effects of extended administration of drotrecogin alfa (activated) compared with placebo on cardiovascular, hematology, hepatic, renal, and respiratory function as assessed by available laboratory and physiologic parameters over the 14-day interval from the start of commercial drug therapy. ? To evaluate the effects of extended administration of drotrecogin alfa (activated) compared with placebo on the concentrations of various biomarkers (e.g., Protein C, D-Dimer, Prothrombin Time) at the start and stop of the extended infusion. ? To investigate the safety profile (e.g. study drug related bleeding events) of an extended infusion of drotrecogin alfa (activated) over a 24-day study.;Primary end point(s): The primary efficacy measurement will be time to resolution of vasopressor-dependent hypotension.;Timepoint(s) of evaluation of this end point: later than 72 hours after initiation of the study drug | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy measurements will be obtained by comparing organ function (assessed by SOFA, including cardiovascular SOFA) between patients administered drotrecogin alfa (activated) or placebo for the extended infusion period and retrospective to 1 day prior to the initiation of commercial drotrecogin alfa (activated). This assessment will be done each day the patient is receiving study drug, in the ICU and hospitalized in the study hospital (up to and including Study Day 14). Biomarker evaluation. All patients will have central laboratory specimens drawn for specific biomarker assessment at the start and end of the study drug infusion. These biomarkers will include D-dimer, Protein C levels and Prothrombin Time. 28-day all cause mortality and in-hospital mortality. All patients will be classified at Day 28 as either ?alive? or ?dead.? Patients who are discharged from the study hospital before Day 28 will be contacted to determine their survival status. For example, a patient who is discharged from the study hospital on Study Day 16 and dies while at home on Study Day 20 will be classified as ?dead.? Patients who die while hospitalized in the study hospital will be classified as ?dead.? Patients who are still hospitalized after Study Day 28 will be followed up through hospital discharge or a maximum of 90 days, whichever comes first, to assess in-hospital mortality.;Timepoint(s) of evaluation of this end point: 90 days | — |
Countries
Afghanistan, Spain, United States
Contacts
Public ContactClinical Operations
Lilly S.A.
Outcome results
None listed