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

This study has been completed.
Sponsor:
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00279214
First received: December 15, 2005
Last updated: August 26, 2009
Last verified: August 2009
History of Changes
Results First Received: October 31, 2008  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Sepsis
Septic Shock
Intervention: Drug: drotrecogin alfa (activated)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Although 22 and 21 patients were randomized to drotrecogin alfa (activated) [DrotA(a)] and control, respectively, 3 patients in DrotA(a) and 2 patients in control did not receive the per-protocol treatment, and as such, they have been excluded from the baseline demographics and the per-protocol efficacy analyses.

Reporting Groups
  Description
Drotrecogin Cohort Group received drotrecogin alfa (activated) per physician-directed therapy
Control Cohort Group did not receive drotrecogin alfa (activated) per physician-directed therapy

Participant Flow:   Overall Study
    Drotrecogin Cohort     Control Cohort  
STARTED     22     21  
COMPLETED     19 [1]   19 [1]
NOT COMPLETED     3     2  
Physician Decision                 3                 2  
[1] Completed means the number of per-protocol patients in the study



  Baseline Characteristics
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Reporting Groups
  Description
Drotrecogin Cohort Group received drotrecogin alfa (activated) per physician-directed therapy
Control Cohort Group did not receive drotrecogin alfa (activated) per physician-directed therapy
Total Total of all reporting groups

Baseline Measures
    Drotrecogin Cohort     Control Cohort     Total  
Number of Participants  
[units: participants]
 		  19     19     38  
Age  
[units: years]
Mean ± Standard Deviation 		  68.0  ± 11.8     65.8  ± 15.0     66.9  ± 13.3  
Gender  
[units: participants]
 		     
Female     8     7     15  
Male     11     12     23  
Region of Enrollment  
[units: participants]
 		     
United States     19     19     38  
Race/Ethnicity  
[units: participants]
 		     
African     1     1     2  
Caucasian     16     15     31  
East Asian     1     0     1  
Hispanic     1     3     4  
Cardiac Index [1]
[units: liters/minute/meters squared]
Mean ± Standard Deviation 		  3.5  ± 1.7     3.3  ± 1.4     3.4  ± 1.6  
Creatinine Clearance [2]
[units: milliliter per minute]
Mean ± Standard Deviation 		  69.2  ± 77.0     29.9  ± 31.1     52.9  ± 64.5  
Cumulative Vasopressor Index (CVI) [3]
[units: units on a scale]
Mean ± Standard Deviation 		  4.3  ± 2.1     4.4  ± 2.4     4.4  ± 2.2  
Lactate Levels [4]
[units: millimoles per Liter]
Mean ± Standard Deviation 		  2.0  ± 1.1     2.6  ± 2.8     2.3  ± 2.1  
Mean Arterial Pressure (MAP)  
[units: mm Hg]
Mean ± Standard Deviation 		  73.5  ± 9.9     72.1  ± 9.4     72.8  ± 9.5  
Mixed Venous Oxygen Saturation [5]
[units: percent saturation mixed venous oxygen]
Mean ± Standard Deviation 		  68.9  ± 15.6     68.9  ± 10.1     68.9  ± 12.9  
Number of Organ Dysfunctions  
[units: number of organ dysfunctions]
Mean ± Standard Deviation 		  2.5  ± 0.8     2.0  ± 0.9     2.3  ± 0.9  
Ratio of Arterial Partial Pressure of Oxygen to Fraction of Inspired Oxygen (PaO2/FiO2)  
[units: mm Hg / percent inspired oxygen]
Mean ( Inter-Quartile Range ) 		  191.8  
  ( 140.0 to 260.0 )   		  248.3  
  ( 181.7 to 330.0 )   		  222.0  
  ( 164.0 to 303.3 )  
Total Sequential Organ Failure Assessment Score [6]
[units: units on a scale]
Mean ± Standard Deviation 		  8.5  ± 2.0     8.3  ± 3.2     8.4  ± 2.6  
[1] Cardiac Index = cardiac output divided by body surface area.
[2] 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.
[3]

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.
[4] Measures of global tissue perfusion and oxygenation were assessed via lactate levels.
[5] Cardiovascular performance measures obtained with a pulmonary catheter as assessed by mixed venous oxygen saturation.
[6] 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).



  Outcome Measures
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1.  Primary:   Cumulative Vasopressor Index (CVI)   [ Time Frame: baseline to 24 hours ]
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2.  Secondary:   Change From Baseline to 96 Hour Endpoint in Cumulative Vasopressor Index (CVI)   [ Time Frame: Baseline, 96 hours ]
  Show Outcome Measure 2

3.  Secondary:   Mean Arterial Pressure   [ Time Frame: baseline to 24 hours ]
  Show Outcome Measure 3

4.  Secondary:   Cardiovascular Performance Measures Obtained With a Pulmonary Artery Catheter - Cardiac Index   [ Time Frame: Baseline to 24 Hours ]
  Show Outcome Measure 4

5.  Secondary:   Lactate Level   [ Time Frame: Baseline to 6 Hours ]
  Show Outcome Measure 5

6.  Secondary:   Microcirculatory Measures From Sidestream Darkfield (SDF) Microscopy - Small Vessel Microvascular Flow Index (MFI)   [ Time Frame: Baseline to 24 Hours ]
  Show Outcome Measure 6

7.  Secondary:   Sequential Organ Failure Assessment (SOFA) Score at Baseline and 24 Hours   [ Time Frame: Baseline and 24 Hours ]
  Show Outcome Measure 7

8.  Secondary:   Change From Baseline in Creatinine Clearance (CrCl) at 24 Hours   [ Time Frame: Baseline and 24 hours ]
  Show Outcome Measure 8

9.  Secondary:   7 Day All-cause In-hospital Mortality   [ Time Frame: baseline to 7 days ]
  Show Outcome Measure 9

10.  Secondary:   Endogenous Protein C Level   [ Time Frame: Baseline to 24 Hours ]
  Show Outcome Measure 10

11.  Secondary:   Mixed Venous Oxygen Saturation   [ Time Frame: Baseline to 24 Hours ]
  Show Outcome Measure 11

12.  Other Pre-specified:   Number of Participants With Bleeding Events   [ Time Frame: baseline to 7 days ]
  Show Outcome Measure 12


  Serious Adverse Events
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  Other Adverse Events
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 1-800-545-5979


No publications provided


ClinicalTrials.gov Identifier: NCT00279214     History of Changes
Other Study ID Numbers: 9944, F1K-US-EVDA
Study First Received: December 15, 2005
Results First Received: October 31, 2008
Last Updated: August 26, 2009
Health Authority: United States: Food and Drug Administration