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

Eli Lilly and Company486 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

486

Conditions

Severe Sepsis

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (47)

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.

Phoenix, Arizona, United States

Scottsdale, Arizona, United States

Fresno, California, United States

Loma Linda, California, United States

Outcomes

Primary Outcomes

Mean Change in Protein C Levels From Day 1 to 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.

Time frame: Day 1, Day 7

Secondary Outcomes

Mean Change in Protein C Level From Study Day 1 to Study Day 7 in Patients With Moderate and Severe Protein C Deficiency

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.

Time frame: Day 1, Day 7

Day 28 All-Cause Mortality

Time frame: Day 0 through Day 28

Hospital Mortality (up to Day 90)

Time frame: Day 0 to hospital discharge or Day 90

28-Day Time Averaged Sequential Organ Failure (SOFA) Score

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.

Time frame: Day 0, Day 28

Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period

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.

Time frame: Day 0 through Day 28

Mortality by Protein C Normalized Versus Not-normalized

Normalization was defined as having 2 consecutive protein C measurements above the lower limit of normal through Study Day 7.

Time frame: 28 days

Stanford, California, United States

Washington D.C., District of Columbia, United States

Orlando, Florida, United States

Idaho Falls, Idaho, United States

Indianapolis, Indiana, United States

Louisville, Kentucky, United States