Investigation of the Efficacy and Safety of Drotrecogin Alfa (Activated) in Pediatric Severe Sepsis

Study Overview
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Brief Summary
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The purposes of this study are to determine: Whether drotrecogin alfa (activated) helps children with severe sepsis survive their condition more often or recover faster than children who do not receive drotrecogin alfa (activated). Whether drotrecogin alfa (activated) minimizes long term disabilities associated with severe sepsis. The side effects that might be associated with drotrecogin alfa (activated) administration to children with severe sepsis.

Detailed Description
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The primary objective was to demonstrate that drotrecogin alfa (activated) compared with placebo reduced severe-sepsis-induced organ dysfunction as assessed by time to complete resolution of a composite of cardiovascular, respiratory, and renal organ failure in pediatric patients with severe sepsis. Secondary objectives included: (1) to assess whether treatment with drotrecogin alfa (activated) reduced 28-day all-cause mortality in pediatric patients with severe sepsis compared with placebo patients, (2) to evaluate the effects of drotrecogin alfa (activated) on individual organ dysfunction (cardiovascular, respiratory, renal, hepatic, hematologic, neurologic, and cutaneous), (3) to demonstrate that drotrecogin alfa (activated) improved patient outcome as assessed by the Pediatric Overall Performance Category (POPC) scale, (4) to demonstrate that drotrecogin alfa (activated) reduced major amputations (at or above the wrist, at or above the ankle, face, and genitals) in pediatric patients with Neisseria meningitidis (proven or suspected) and/or purpura fulminans, (5) to demonstrate that drotrecogin alfa (activated) had antithrombotic and anti-inflammatory properties. The safety objective was to evaluate whether drotrecogin alfa (activated) had an acceptable safety profile when administered to pediatric patients with severe sepsis.

Official Title
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Investigation of the Efficacy and Safety of Drotrecogin Alfa (Activated) in Pediatric Severe Sepsis

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: Suspected or proven acute infection. Abnormally high or low core body temperature Cardiovascular dysfunction which requires the use of vasoactive drugs (such as, dopamine, dobutamine, epinephrine) and is the result of severe sepsis. Respiratory dysfunction which requires the use of mechanical ventilation and is the result of severe sepsis. Exclusion Criteria: Patients at increased risk of bleeding. Patients at high risk for an intracranial bleed. Patients who have undergone a bone marrow transplant. Patients with end-stage renal disease. Patients whose family or primary care physician is unwilling to allow transfusion of blood products.

Ages Eligible for Study
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Maximum Age: 17 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: 1<br>24 microgram/kg/hr for 96 hours (+ or - 1 hour) | Drug: Drotrecogin alfa (activated)<br> <br> * Other names: Xigris;|
| Placebo Comparator: 2<br>0.9% sodium chloride | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| That drotrecogin alfa (activated) compared with placebo reduces severe-sepsis-induced organ dysfunction |  | 3 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All cause mortality data |  | 3 Years | 
| The effects of drotrecogin alfa (activated) on individual organ dysfunction |  | 3 Years | 
| Amputation reduction (at or above the wrist, at or above the ankle, face, and genitals)in pediatric patients with Neisseria meningitidis |  | 3 Years | 
| Demonstrate that drotrecogin alfa (activated) has antithrombotic and anti-inflammatory properties. |  | 3 Years |