Efficacy and Safety of Drotrecogin Alfa (Activated) in Adult Patients With Septic Shock

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00604214
First received: January 24, 2008
Last updated: August 20, 2012
Last verified: August 2012

January 24, 2008
August 20, 2012
March 2008
September 2011   (final data collection date for primary outcome measure)
28-Day All-Cause Mortality [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
Expressed as percentage of participants who died from any cause at Day 28 endpoint.
Treatment with drotrecogin alfa (activated)compared with placebo reduces 28-day mortality in adult patients with septic shock [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00604214 on ClinicalTrials.gov Archive Site
  • 28-Day All-Cause Mortality in Participants With Severe Protein C Deficiency [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    Expressed as percentage of participants who died from any cause at Day 28 endpoint. Participants with severe protein C deficiency are those who had a protein C level ≤ half the lower limit of normal (LLN) (≤40%).
  • Average Cardiovascular Sequential Organ Failure Assessment (SOFA) Score Day 1 Through Day 28 [ Time Frame: Day 1 through Day 28 ] [ Designated as safety issue: No ]
    Scores range from 0 (normal) to 4 (organ failure) with an increasing score indicating increasing cardiovascular dysfunction. A non-surviving participant receives a score of 4 (worst score) for the day of death and every day thereafter.
  • Average Respiratory Sequential Organ Failure Assessment (SOFA) Score Day 1 Through Day 28 [ Time Frame: Day 1 through Day 28 ] [ Designated as safety issue: No ]
    Scores range from 0 (normal) to 4 (organ failure) with an increasing score indicating increasing respiratory dysfunction. A non-surviving participant receives a score of 4 (worst score) for the day of death and every day thereafter.
  • Average Renal Sequential Organ Failure Assessment (SOFA) Score Day 1 Through Day 28 [ Time Frame: Day 1 through Day 28 ] [ Designated as safety issue: No ]
    Scores range from 0 (normal) to 4 (organ failure) with an increasing score indicating increasing renal dysfunction. A non-surviving participant receives a score of 4 (worst score) for the day of death and every day thereafter.
  • 90-Day Mortality [ Time Frame: Day 90 ] [ Designated as safety issue: No ]
    Expressed as percentage of participants who died from any cause at Day 90 endpoint.
  • 180-Day Mortality [ Time Frame: Day 180 ] [ Designated as safety issue: No ]
    Expressed as percentage of participants who died from any cause at Day 180 endpoint.
  • Median Survival Time [ Time Frame: Day 180 ] [ Designated as safety issue: No ]
  • EuroQoL Questionnaire-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Scores at Baseline, Days 28, 90 and 180 [ Time Frame: Baseline and Days 28 and 90 and 180 ] [ Designated as safety issue: No ]
    EQ-5D VAS assesses caregiver's impression of participant's overall health state. Scores range from 0 (worst health state) to 100 (best health state), with higher scores indicating a better health state.
  • EuroQoL Questionnaire-5 Dimensions (EQ-5D) Total Scores at Baseline, Days 28, 90 and 180 [ Time Frame: Baseline and Days 28 and 90 and 180 ] [ Designated as safety issue: No ]
    The EQ-5D is used to assess participant's overall health. Consists of 5 items: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each item has 3 severity levels (no, some, severe problems). Calculated from EQ-5D, total scores (United States [US] Index Score) range from 0 (worst quality of life) to 1.00 (best quality of life).
  • Quality of Life Short Form-12 (SF-12) Scores at Baseline, Days 28, 90 and 180 [ Time Frame: Baseline and Days 28 and 90 and 180 ] [ Designated as safety issue: No ]
    SF-12 was used as an instrument to measure participants' physical wellbeing (physical component) and mental wellbeing (mental component). Scores for each component range from 0-100, with 0= lowest wellbeing, and 100=highest wellbeing.
  • Percentage of Participants Discontinued Due to Adverse Events Any Time From Baseline Through Day 28 Endpoint [ Time Frame: Baseline through Day 28 ] [ Designated as safety issue: Yes ]
  • To demonstrate that treatment with drotrecogin alfa (activated) reduces 28-day all-cause mortality in adult patients with septic shock and severe protein C deficiency compared with placebo. [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Treatment with drotrecogin alfa (activated) improves cardiovascular, respiratory, and renal organ function compared with placebo. [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Drotrecogin alfa (activated) has an acceptable safety profile in this patient population. [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
Percentage of Participants With Serious Bleeding Events Within System Organ Class Any Time From Baseline Through Day 28 [ Time Frame: Baseline through Day 28 ] [ Designated as safety issue: Yes ]
Percentage of participants who experienced serious bleeding events are reported by System Organ Class (SOC) term based on MedDRA 14.0. For a bleeding to qualify as a serious event, it would have to meet the standard definition of a serious adverse event or be a central nervous system bleeding or a bleeding event that lead to administration of ≥3 units packed red blood cells/day for 2 consecutive days.
Not Provided
 
Efficacy and Safety of Drotrecogin Alfa (Activated) in Adult Patients With Septic Shock
A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 3 Study of Drotrecogin Alfa (Activated) Administered as a Continuous 96-hr Infusion to Adult Patients With Septic Shock

The purpose of this placebo-controlled study is to determine if drotrecogin alfa (activated) treatment provides significant mortality reduction improvement in patients with septic shock compared with placebo treatment in patients receiving the current standard of care for septic shock. This study will also assess the effectiveness of drotrecogin alfa (activated) in reducing 28-day mortality in patients with septic shock and concomitant severe protein C deficiency.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Sepsis
  • Drug: Drotrecogin alfa (activated)
    24 microgram/kilogram/hour, intravenous, 96 hours (hr)
    Other Names:
    • LY203638
    • Xigris
  • Drug: Placebo
    0.9% sodium chloride, intravenous, 96 hours
  • Experimental: Drotrecogin alfa (activated)
    Intervention: Drug: Drotrecogin alfa (activated)
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Ranieri VM, Thompson BT, Barie PS, Dhainaut JF, Douglas IS, Finfer S, Gårdlund B, Marshall JC, Rhodes A, Artigas A, Payen D, Tenhunen J, Al-Khalidi HR, Thompson V, Janes J, Macias WL, Vangerow B, Williams MD; PROWESS-SHOCK Study Group. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med. 2012 May 31;366(22):2055-64. doi: 10.1056/NEJMoa1202290. Epub 2012 May 22.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1696
February 2012
September 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Must be 18 years or older
  • Must have evidence of infection
  • Must have systemic inflammatory response syndrome (SIRS)
  • Must have vasopressor-dependent septic shock

Exclusion Criteria:

  • Have received vasopressor therapy (at any dose) for greater than 24 hours prior to the start of study drug
  • Have sepsis-induced organ dysfunction for greater than 36 hours prior to the start of the study drug infusion
  • Have single organ dysfunction and recent surgery (within 30 days of study entry)
  • Have had surgery performed within the 12-hour period immediately preceding the study drug infusion, or are postoperative with evidence of active bleeding, or have planned or anticipated surgery during the infusion period
  • Are not expected to survive 28 days given their preexisting uncorrectable medical condition
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Belgium,   Brazil,   Canada,   Czech Republic,   Finland,   France,   Germany,   India,   Italy,   Mexico,   Netherlands,   New Zealand,   Portugal,   Spain,   Switzerland,   United Kingdom
 
NCT00604214
11940, F1K-MC-EVDP
Yes
Eli Lilly and Company
Eli Lilly and Company
Not Provided
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
Eli Lilly and Company
August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP