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

Phase 3

Completed

• Conditions: Sepsis
• Interventions: Drug: Placebo; Drug: Drotrecogin alfa (activated)

• Registration Number: NCT00604214
• Lead Sponsor: Eli Lilly and Company

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2008-01-24
• Study First Submitted QC: 2008-01-24
• Study First Posted: 2008-01-30
• Study Start: 2008-03
• Primary Completion: 2011-09
• Study Completion: 2012-02
• Status Verified: 2012-08
• Results First Submitted: 2012-08-20
• Results First Submitted QC: 2012-08-20
• Last Update Submitted: 2012-08-20
• Results First Posted: 2012-09-18
• Last Update Posted: 2012-09-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1696

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Drotrecogin alfa (activated)	Drotrecogin alfa (activated)	-

Primary Outcome Measures

Name	Time	Method
28-Day All-Cause Mortality	Day 28	Expressed as percentage of participants who died from any cause at Day 28 endpoint.

Secondary Outcome Measures

Name	Time	Method
Median Survival Time	Day 180
Average Respiratory Sequential Organ Failure Assessment (SOFA) Score Day 1 Through Day 28	Day 1 through Day 28	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.
180-Day Mortality	Day 180	Expressed as percentage of participants who died from any cause at Day 180 endpoint.
Quality of Life Short Form-12 (SF-12) Scores at Baseline, Days 28, 90 and 180	Baseline and Days 28 and 90 and 180	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.
28-Day All-Cause Mortality in Participants With Severe Protein C Deficiency	Day 28	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	Day 1 through Day 28	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 Renal Sequential Organ Failure Assessment (SOFA) Score Day 1 Through Day 28	Day 1 through Day 28	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	Day 90	Expressed as percentage of participants who died from any cause at Day 90 endpoint.
EuroQoL Questionnaire-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Scores at Baseline, Days 28, 90 and 180	Baseline and Days 28 and 90 and 180	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	Baseline and Days 28 and 90 and 180	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).
Percentage of Participants Discontinued Due to Adverse Events Any Time From Baseline Through Day 28 Endpoint	Baseline through Day 28

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.; 🇬🇧 London, United Kingdom