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Evaluate Protein C Levels in Severe Sepsis Patients on Drotrecogin Alfa (Activated)

This study has been completed.
Sponsor:
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00386425
First received: October 6, 2006
Last updated: November 18, 2010
Last verified: November 2010
History of Changes
  Purpose

In this trial, patients with severe sepsis and low protein C levels will receive drotrecogin alfa (activated) at the normal, approved dose and time of administration [24 microgram/kilogram/hour (mcg/kg/hour) for 96 hours] or will receive the normal, approved dose or higher doses than the approved dose for a longer administration time. After the drug administration is complete, the protein C levels from the patients receiving the normal, approved dose will be compared to protein C levels from patients receiving the normal, approved dose or higher dose for a longer duration to determine if the protein C levels improve faster if given higher dose and/or longer administration time.

Note: The protocol was amended to remove the option of shorter infusion durations.


Condition Intervention Phase
Severe Sepsis
 Drug: Drotrecogin alfa (activated)
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2 Study to Evaluate Dose and Duration of Treatment of Drotrecogin Alfa (Activated) Using Serial Measurements of Protein C in Patients With Severe Sepsis and Multiple Organ Dysfunction

Resource links provided by NLM:

MedlinePlus related topics: Sepsis
U.S. FDA Resources

Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Mean Change in Protein C Levels From Day 1 to Day 7 [ Time Frame: Day 1, Day 7 ] [ Designated as safety issue: No ]
    Mean change in protein C from Study Day 1 to Study Day 7 was tested using an unadjusted two-sample t-test with a two-sided alpha of 0.05. To be included in the primary analysis, Intention-to-Treat (ITT) patients must have at least 1 protein C value available at 24 hours or earlier and at least 1 protein C value at a post-24-hour timepoint.


Secondary Outcome Measures:
  • Mean Change in Protein C Level From Study Day 1 to Study Day 7 in Patients With Moderate and Severe Protein C Deficiency [ Time Frame: Day 1, Day 7 ] [ Designated as safety issue: No ]

    Moderate Protein C Deficiency: A protein C level greater than half the lower limit of normal.

    Severe Protein C Deficiency: A protein C level less than or equal to half the lower limit of normal.


  • Day 28 All-Cause Mortality [ Time Frame: Day 0 through Day 28 ] [ Designated as safety issue: No ]
  • Hospital Mortality (up to Day 90) [ Time Frame: Day 0 to hospital discharge or Day 90 ] [ Designated as safety issue: No ]
  • 28-Day Time Averaged Sequential Organ Failure (SOFA) Score [ Time Frame: Day 0, Day 28 ] [ Designated as safety issue: No ]
    The presence of 5 organ dysfunctions (cardiovascular, respiratory, renal, hepatic, coagulation) was assessed using a Sequential Organ Failure Assessment (SOFA) score. Each organ has a possible dysfunction score of 0 to 4, for a total SOFA score range of 0 (no organ dysfunction) to 20 (all organs with dysfunction). SOFA scores were time-averaged.

  • Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period [ Time Frame: Day 0 through Day 28 ] [ Designated as safety issue: Yes ]
    Serious bleeding events (SBE): intracranial hemorrhage, life-threatening or fatal bleed, or bleeding event assessed as an SAE. Patients may have multiple events with onset in different time periods. SAEs include SBEs. The 3 SBEs in Alternative-Moderate Deficiency arm (days 5-8) occurred after completion of study drug infusion. One event (pleural haemorrhage) occurred same day of completion of infusion and 2 events (cerebral haemorrhage, shock haemorrhagic) occurred day after completion.

  • Mortality by Protein C Normalized Versus Not-normalized [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Normalization was defined as having 2 consecutive protein C measurements above the lower limit of normal through Study Day 7.


Enrollment: 486
Study Start Date: November 2006
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Standard therapy
24 microgram/kilogram/hour (mcg/kg/hr) for 24 hours, followed by 24 mcg/kg/hr for an additional 72 hours
 Drug: Drotrecogin alfa (activated)
intravenous
Other Names:
  • Xigris
  • LY203638
Experimental: Alternative therapy:moderate protein C deficiency
24 mcg/kg/hr for 24 hours, followed by 24 mcg/kg/hr for an additional 48 to 144 hours (original protocol) or an additional 72 to 144 hours (amended protocol)
 Drug: Drotrecogin alfa (activated)
intravenous
Other Names:
  • Xigris
  • LY203638
Experimental: Alternative therapy:severe protein C deficiency
24 mcg/kg/hr for 24 hours, followed by 30 or 36 mcg/kg/hr for 48 to 144 hours (original protocol) or an additional 72 to 144 hours (amended protocol)
 Drug: Drotrecogin alfa (activated)
intravenous
Other Names:
  • Xigris
  • LY203638

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must be 18 years or older
  • Must have a suspected or proven infection
  • Must have two or more sepsis-associated organ dysfunctions

Exclusion Criteria:

  • Documented multiple organ dysfunction greater than 24 hours prior to start of study drug
  • Actual body weight less than 30 kg or more than 135 kg
  • Platelet count less than 30,000/mm^3
  • Active internal bleeding or at increased risk of bleeding
  • Not expected to survive 28 days given the patient's pre-existing uncorrectable medical condition
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00386425

  Show 47 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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
  More Information

No publications provided by Eli Lilly and Company

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT00386425     History of Changes
Other Study ID Numbers: 10553, F1K-MC-EVDK
Study First Received: October 6, 2006
Results First Received: August 26, 2010
Last Updated: November 18, 2010
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Sepsis
Toxemia
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Protein C
Drotrecogin alfa activated
Anticoagulants
 Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on May 16, 2013