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

Primary Purpose

Sepsis, Septic Shock

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
drotrecogin alfa (activated)
Sponsored by
Eli Lilly and Company
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sepsis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • 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.
  • 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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Mean Arterial Pressure
Cardiovascular Performance Measures Obtained With a Pulmonary Artery Catheter - Cardiac Index
Cardiac Index = cardiac output divided by body surface area.
Lactate Level
Measures of global tissue perfusion and oxygenation were assessed via lactate levels.
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).
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).
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.
7 Day All-cause In-hospital Mortality
Endogenous Protein C Level
Mixed Venous Oxygen Saturation
Cardiovascular performance measures obtained with a pulmonary catheter as assessed by mixed venous oxygen saturation.

Full Information

First Posted
December 15, 2005
Last Updated
August 26, 2009
Sponsor
Eli Lilly and Company
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1. Study Identification

Unique Protocol Identification Number
NCT00279214
Brief Title
Hemodynamic and Perfusion Response to Drotrecogin Alfa (Activated) in Patients With Septic Shock
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2009
Overall Recruitment Status
Completed
Study Start Date
November 2005 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
November 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Eli Lilly and Company

4. Oversight

5. Study Description

Brief Summary
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sepsis, Septic Shock

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
43 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
drotrecogin alfa (activated)
Primary Outcome Measure Information:
Title
Cumulative Vasopressor Index (CVI)
Description
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.
Time Frame
baseline to 24 hours
Secondary Outcome Measure Information:
Title
Change From Baseline to 96 Hour Endpoint in Cumulative Vasopressor Index (CVI)
Description
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.
Time Frame
Baseline, 96 hours
Title
Mean Arterial Pressure
Time Frame
baseline to 24 hours
Title
Cardiovascular Performance Measures Obtained With a Pulmonary Artery Catheter - Cardiac Index
Description
Cardiac Index = cardiac output divided by body surface area.
Time Frame
Baseline to 24 Hours
Title
Lactate Level
Description
Measures of global tissue perfusion and oxygenation were assessed via lactate levels.
Time Frame
Baseline to 6 Hours
Title
Microcirculatory Measures From Sidestream Darkfield (SDF) Microscopy - Small Vessel Microvascular Flow Index (MFI)
Description
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).
Time Frame
Baseline to 24 Hours
Title
Sequential Organ Failure Assessment (SOFA) Score at Baseline and 24 Hours
Description
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).
Time Frame
Baseline and 24 Hours
Title
Change From Baseline in Creatinine Clearance (CrCl) at 24 Hours
Description
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.
Time Frame
Baseline and 24 hours
Title
7 Day All-cause In-hospital Mortality
Time Frame
baseline to 7 days
Title
Endogenous Protein C Level
Time Frame
Baseline to 24 Hours
Title
Mixed Venous Oxygen Saturation
Description
Cardiovascular performance measures obtained with a pulmonary catheter as assessed by mixed venous oxygen saturation.
Time Frame
Baseline to 24 Hours
Other Pre-specified Outcome Measures:
Title
Number of Participants With Bleeding Events
Description
Serious bleeding event resulted in one of following outcomes, or was significant for any reason: initial/ prolonged inpatient hospitalization; life-threatening experience; persistent or significant disability/incapacity; congenital anomaly/birth defect. Intracranial hemorrhage was also considered serious bleeding event.
Time Frame
baseline to 7 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-651-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
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.
City
Camden
State/Province
New Jersey
ZIP/Postal Code
08103
Country
United States
Facility Name
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.
City
Akron
State/Province
Ohio
ZIP/Postal Code
44307
Country
United States

12. IPD Sharing Statement

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

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