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

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 3 Study of Drotrecogin Alfa (Activated) Administered as a Continuous 96-hr Infusion to Adult Patients With Septic Shock

Conditions
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Sepsis

Intervention / Treatment
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* Drug: Drotrecogin alfa (activated)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drotrecogin alfa (activated)<br> | Drug: Drotrecogin alfa (activated)<br>* 24 microgram/kilogram/hour, intravenous, 96 hours (hr)<br>* Other names: Xigris;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 0.9% sodium chloride, intravenous, 96 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28-Day All-Cause Mortality | Expressed as percentage of participants who died from any cause at Day 28 endpoint. | Day 28 | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sepsis, Septic shock