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
  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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 August 28, 2014