Hemodynamic and Perfusion Response to Drotrecogin Alfa (Activated) in Patients With Septic Shock

Study Overview
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Brief Summary
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The study will evaluate the vasopressor requirement, hemodynamic response and measures of tissue perfusion in patients with septic shock receiving an infusion of drotrecogin alfa (activated) compared to patients not receiving drotrecogin alfa (activated).

Official Title
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An Evaluation of Vasopressor Requirement, Hemodynamic Response and Measures of Tissue Perfusion With the Administration of Drotrecogin Alfa (Activated) as Part of Physician-Directed Therapy in Patients With Septic Shock

Conditions
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Sepsis, Septic Shock

Intervention / Treatment
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* Drug: drotrecogin alfa (activated)


Participation Criteria
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Eligibility Criteria
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Inclusion: 18 years of age or older with a diagnosis of septic shock presence of a pulmonary artery catheter (or central venous catheters) requiring vasopressor support despite adequate fluid resuscitation an intravenous steroid administered for septic shock, except for those patients who were tested and are responders to a corticotropin stimulation test, or patients who do not receive a steroid due to the clinical judgment of the treating physician, based on an alternate assessment (e.g. normal baseline cortisol). Exclusion: Onset of first-sepsis induced organ dysfunction is greater than 24 hours from the time of informed consent Baseline measurements of pulmonary artery occlusive pressure (PAOP) < 12 mmHg or a central venous pressure (CVP) < 8 mmHg Patient requires continuous oxygen therapy by face-mask The presence of an advanced directive to withhold life-sustaining treatment, with the exception of a directive to withhold chest compressions only Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry Weight > 200 kg Are moribund (not expected to survive 24 hours) Are pregnant or are lactating and the milk is to be ingested by the infant (pregnancy status must be verified by urine or serum testing) Have not completed written informed consent signed by the patient or the patient's legal representative.

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: drotrecogin alfa (activated)|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Vasopressor Index (CVI) | CVI is sum of rankings for all vasopressors being used by patient at given time. Based on relative potency and dosing range for each vasopressor, each vasopressor was assigned ranking of 1 (low dosage) to 4 (high dosage). Range of CVI is between 1 and 20. | baseline to 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 96 Hour Endpoint in Cumulative Vasopressor Index (CVI) | CVI is sum of rankings for all vasopressors being used by patient at given time. Based on relative potency and dosing range for each vasopressor, each vasopressor was assigned ranking of 1 (low dosage) to 4 (high dosage). Range of CVI is between 1 and 20. | Baseline, 96 hours | 
| Mean Arterial Pressure |  | baseline to 24 hours | 
| Cardiovascular Performance Measures Obtained With a Pulmonary Artery Catheter - Cardiac Index | Cardiac Index = cardiac output divided by body surface area. | Baseline to 24 Hours | 
| Lactate Level | Measures of global tissue perfusion and oxygenation were assessed via lactate levels. | Baseline to 6 Hours | 
| Microcirculatory Measures From Sidestream Darkfield (SDF) Microscopy - Small Vessel Microvascular Flow Index (MFI) | Per vessel category (and per quadrant), scored flow as follows: no flow=0, intermediate flow=1, sluggish flow=2, continuous flow=3. The MFI per vessel category calculated with formula (Q1+Q2+Q3+Q4)/4. Scores could range from 0 (sluggish flow) to 3 (continuous flow). | Baseline to 24 Hours | 
| Sequential Organ Failure Assessment (SOFA) Score at Baseline and 24 Hours | 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). | Baseline and 24 Hours | 
| Change From Baseline in Creatinine Clearance (CrCl) at 24 Hours | CrCl = (urine creatinine*urine volume)/(plasma creatinine*time period of urine collection). Corrected CrCl = CrCl*1.73/body surface area. Change in CrCl = Endpoint minus baseline. | Baseline and 24 hours | 
| 7 Day All-cause In-hospital Mortality |  | baseline to 7 days | 
| Endogenous Protein C Level |  | Baseline to 24 Hours | 
| Mixed Venous Oxygen Saturation | Cardiovascular performance measures obtained with a pulmonary catheter as assessed by mixed venous oxygen saturation. | Baseline to 24 Hours |