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

Phase 2

Completed

• Conditions: Severe Sepsis
• Interventions: Drug: Drotrecogin alfa (activated)

• Registration Number: NCT00386425
• Lead Sponsor: Eli Lilly and Company

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2006-10-06
• Study First Submitted QC: 2006-10-10
• Study First Posted: 2006-10-11
• Study Start: 2006-11
• Primary Completion: 2009-08
• Study Completion: 2009-08
• Results First Submitted: 2010-08-26
• Status Verified: 2010-11
• Results First Submitted QC: 2010-11-18
• Last Update Submitted: 2010-11-18
• Results First Posted: 2010-12-16
• Last Update Posted: 2010-12-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 486

Inclusion Criteria

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard therapy	Drotrecogin alfa (activated)	24 microgram/kilogram/hour (mcg/kg/hr) for 24 hours, followed by 24 mcg/kg/hr for an additional 72 hours
Alternative therapy:moderate protein C deficiency	Drotrecogin alfa (activated)	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)
Alternative therapy:severe protein C deficiency	Drotrecogin alfa (activated)	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)

Primary Outcome Measures

Name	Time	Method
Mean Change in Protein C Levels From Day 1 to Day 7	Day 1, Day 7	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

Name	Time	Method
Mean Change in Protein C Level From Study Day 1 to Study Day 7 in Patients With Moderate and Severe Protein C Deficiency	Day 1, Day 7	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	Day 0 through Day 28
Hospital Mortality (up to Day 90)	Day 0 to hospital discharge or Day 90
28-Day Time Averaged Sequential Organ Failure (SOFA) Score	Day 0, Day 28	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	Day 0 through Day 28	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	28 days	Normalization was defined as having 2 consecutive protein C measurements above the lower limit of normal through Study Day 7.

Trial Locations

Locations (1)

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.; 🇬🇧 Birmingham, West Midlands, United Kingdom