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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00604214
First received: January 24, 2008
Last updated: August 20, 2012
Last verified: August 2012
Results First Received: August 20, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Sepsis
Interventions: Drug: Drotrecogin alfa (activated)
Drug: Placebo

  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
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
Drotrecogin Alfa (Activated) 24 microgram/kilogram/hour, intravenous, 96 hours
Placebo 0.9% sodium chloride, intravenous, 96 hours

Participant Flow for 3 periods

Period 1:   Baseline to Day 28
    Drotrecogin Alfa (Activated)   Placebo
STARTED   851   845 
Received Study Drug   833   833 
COMPLETED   623   632 
NOT COMPLETED   228   213 
Death                223                202 
Lost to Follow-up                2                4 
Withdrawal by Subject                3                7 

Period 2:   Day 29 to Day 90
    Drotrecogin Alfa (Activated)   Placebo
STARTED   623   632 
COMPLETED   555   553 
NOT COMPLETED   68   79 
Death                64                67 
Lost to Follow-up                4                6 
Withdrawal by Subject                0                6 

Period 3:   Day 91 to Day 180
    Drotrecogin Alfa (Activated)   Placebo
STARTED   555   553 
COMPLETED   529   521 
NOT COMPLETED   26   32 
Death                19                23 
Lost to Follow-up                6                8 
Withdrawal by Subject                1                1 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups
  Description
Drotrecogin Alfa (Activated) 24 microgram/kilogram/hour, intravenous, 96 hours
Placebo 0.9% sodium chloride, intravenous, 96 hours
Total Total of all reporting groups

Baseline Measures
   Drotrecogin Alfa (Activated)   Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 851   845   1696 
Age 
[Units: Years]
Mean (Standard Deviation)
 63.42  (15.42)   62.70  (16.41)   63.06  (15.92) 
Gender 
[Units: Participants]
     
Female   360   379   739 
Male   491   466   957 
Race/Ethnicity, Customized 
[Units: Participants]
     
Aboriginal/Torres Strait Islander   2   6   8 
African   30   27   57 
Caucasian   740   721   1461 
East Asian/Pacific   21   10   31 
Hispanic   21   32   53 
Native American   3   4   7 
West Asian (Indian Subcontinent)   34   45   79 
Region of Enrollment 
[Units: Participants]
     
Portugal   3   5   8 
United States   78   82   160 
Finland   45   42   87 
Spain   87   84   171 
Switzerland   8   10   18 
United Kingdom   44   49   93 
Italy   54   53   107 
India   40   41   81 
France   235   229   464 
Czech Republic   30   24   54 
Mexico   7   7   14 
Canada   36   43   79 
Brazil   18   18   36 
Belgium   69   70   139 
Australia   36   28   64 
Netherlands   15   15   30 
Germany   22   23   45 
New Zealand   24   22   46 
Primary Site of Infection 
[Units: Participants]
     
Abdomen   263   246   509 
Blood   40   25   65 
Bone   2   2   4 
Central Nervous System   11   9   20 
Head   2   3   5 
Heart   3   3   6 
Lung   369   375   744 
Other   11   17   28 
Pleura   2   5   7 
Reproductive Tract   2   2   4 
Skin or Skin Structure   48   45   93 
Urinary Tract   97   112   209 
Unknown   1   1   2 
Cardiovascular Sequential Organ Failure Assessment (SOFA) Score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 3.91  (0.32)   3.89  (0.35)   3.90  (0.33) 
[1] Scores range from 0 (normal) to 4 (organ failure) with an increasing score indicating increasing cardiovascular dysfunction. There were 12 participants in drotrecogin alfa (activated) and 14 participants in placebo who were unspecified and were not included in the calculation of mean and standard deviation.
Respiratory Sequential Organ Failure Assessment (SOFA) Score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 2.78  (1.07)   2.74  (1.08)   2.76  (1.08) 
[1] Scores range from 0 (normal) to 4 (organ failure) with an increasing score indicating increasing respiratory dysfunction. There were 35 participants in drotrecogin alfa (activated) and 34 participants in placebo who were unspecified and were not included in the calculation of mean and standard deviation.
Renal Sequential Organ Failure Assessment (SOFA) Score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 1.67  (1.33)   1.60  (1.34)   1.63  (1.33) 
[1] Scores range from 0 (normal) to 4 (organ failure) with an increasing score indicating increasing renal dysfunction. There were 12 participants in drotrecogin alfa (activated) and 17 participants in placebo who were unspecified and were not included in the calculation of mean and standard deviation.
Coagulation Sequential Organ Failure Assessment (SOFA) Score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 0.76  (0.97)   0.71  (0.96)   0.74  (0.96) 
[1] Scores range from 0 (normal) to 4 (organ failure) with an increasing score indicating worsening coagulopathy (decreasing platelet counts). There were 11 participants in drotrecogin alfa (activated) and 17 participants in placebo who were unspecified and were not included in the calculation of mean and standard deviation.
Liver Sequential Organ Failure Assessment (SOFA) Score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 0.55  (0.85)   0.53  (0.88)   0.54  (0.87) 
[1] Scores range from 0 (normal) to 4 (organ failure) with an increasing score indicating increasing liver dysfunction. There were 61 participants in drotrecogin alfa (activated) and 70 participants in placebo who were unspecified and were not included in the calculation of mean and standard deviation.
Acute Physiology and Chronic Health Evaluation II (APACHE II) Score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 25.17  (8.06)   25.45  (8.14)   25.31  (8.10) 
[1] Acute Physiology and Chronic Health Evaluation II (APACHE II) score is a severity-of-disease classification system. Scores range from 0 to 71. Higher scores correspond to more severe disease and a higher risk of death. There were 4 participants in drotrecogin alfa (activated) and 1 participant in placebo who were unspecified and were not included in the calculation of mean and standard deviation.


  Outcome Measures
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1.  Primary:   28-Day All-Cause Mortality   [ Time Frame: Day 28 ]

2.  Secondary:   28-Day All-Cause Mortality in Participants With Severe Protein C Deficiency   [ Time Frame: Day 28 ]

3.  Secondary:   Average Cardiovascular Sequential Organ Failure Assessment (SOFA) Score Day 1 Through Day 28   [ Time Frame: Day 1 through Day 28 ]

4.  Secondary:   Average Respiratory Sequential Organ Failure Assessment (SOFA) Score Day 1 Through Day 28   [ Time Frame: Day 1 through Day 28 ]

5.  Secondary:   Average Renal Sequential Organ Failure Assessment (SOFA) Score Day 1 Through Day 28   [ Time Frame: Day 1 through Day 28 ]

6.  Secondary:   90-Day Mortality   [ Time Frame: Day 90 ]

7.  Secondary:   180-Day Mortality   [ Time Frame: Day 180 ]

8.  Secondary:   Median Survival Time   [ Time Frame: Day 180 ]

9.  Secondary:   EuroQoL Questionnaire-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Scores at Baseline, Days 28, 90 and 180   [ Time Frame: Baseline and Days 28 and 90 and 180 ]

10.  Secondary:   EuroQoL Questionnaire-5 Dimensions (EQ-5D) Total Scores at Baseline, Days 28, 90 and 180   [ Time Frame: Baseline and Days 28 and 90 and 180 ]

11.  Secondary:   Quality of Life Short Form-12 (SF-12) Scores at Baseline, Days 28, 90 and 180   [ Time Frame: Baseline and Days 28 and 90 and 180 ]

12.  Secondary:   Percentage of Participants Discontinued Due to Adverse Events Any Time From Baseline Through Day 28 Endpoint   [ Time Frame: Baseline through Day 28 ]

13.  Other Pre-specified:   Percentage of Participants With Serious Bleeding Events Within System Organ Class Any Time From Baseline Through Day 28   [ Time Frame: Baseline through Day 28 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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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 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 more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


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


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00604214     History of Changes
Other Study ID Numbers: 11940
F1K-MC-EVDP ( Other Identifier: Eli Lilly and Company )
Study First Received: January 24, 2008
Results First Received: August 20, 2012
Last Updated: August 20, 2012
Health Authority: United States: Food and Drug Administration