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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  
Number of Participants  
[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  
Respiratory Sequential Organ Failure Assessment (SOFA) Score [2]
[units: units on a scale]
Mean ± Standard Deviation
  2.78  ± 1.07     2.74  ± 1.08     2.76  ± 1.08  
Renal Sequential Organ Failure Assessment (SOFA) Score [3]
[units: units on a scale]
Mean ± Standard Deviation
  1.67  ± 1.33     1.60  ± 1.34     1.63  ± 1.33  
Coagulation Sequential Organ Failure Assessment (SOFA) Score [4]
[units: units on a scale]
Mean ± Standard Deviation
  0.76  ± 0.97     0.71  ± 0.96     0.74  ± 0.96  
Liver Sequential Organ Failure Assessment (SOFA) Score [5]
[units: units on a scale]
Mean ± Standard Deviation
  0.55  ± 0.85     0.53  ± 0.88     0.54  ± 0.87  
Acute Physiology and Chronic Health Evaluation II (APACHE II) Score [6]
[units: units on a scale]
Mean ± Standard Deviation
  25.17  ± 8.06     25.45  ± 8.14     25.31  ± 8.10  
[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.
[2] 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.
[3] 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.
[4] 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.
[5] 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.
[6] 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


No publications provided by Eli Lilly and Company

Publications automatically indexed to this study:

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00604214     History of Changes
Other Study ID Numbers: 11940, F1K-MC-EVDP
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