Efficacy and Safety of Drotrecogin Alfa (Activated) in Adult Patients With Septic Shock
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT00604214
Collaborator
(none)
1,696
150
2
47
11.3
0.2
Study Details
Study Description
Brief Summary
The purpose of this placebo-controlled study is to determine if drotrecogin alfa (activated) treatment provides significant mortality reduction improvement in patients with septic shock compared with placebo treatment in patients receiving the current standard of care for septic shock. This study will also assess the effectiveness of drotrecogin alfa (activated) in reducing 28-day mortality in patients with septic shock and concomitant severe protein C deficiency.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
1696 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 3 Study of Drotrecogin Alfa (Activated) Administered as a Continuous 96-hr Infusion to Adult Patients With Septic Shock
Study Start Date
:
Mar 1, 2008
Actual Primary Completion Date
:
Sep 1, 2011
Actual Study Completion Date
:
Feb 1, 2012
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Drotrecogin alfa (activated)
|
Drug: Drotrecogin alfa (activated)
24 microgram/kilogram/hour, intravenous, 96 hours (hr)
Other Names:
|
| Placebo Comparator: Placebo
|
Drug: Placebo
0.9% sodium chloride, intravenous, 96 hours
|
Outcome Measures
Primary Outcome Measures
- 28-Day All-Cause Mortality [Day 28]
Expressed as percentage of participants who died from any cause at Day 28 endpoint.
Secondary Outcome Measures
- 28-Day All-Cause Mortality in Participants With Severe Protein C Deficiency [Day 28]
Expressed as percentage of participants who died from any cause at Day 28 endpoint. Participants with severe protein C deficiency are those who had a protein C level ≤ half the lower limit of normal (LLN) (≤40%).
- Average Cardiovascular Sequential Organ Failure Assessment (SOFA) Score Day 1 Through Day 28 [Day 1 through Day 28]
Scores range from 0 (normal) to 4 (organ failure) with an increasing score indicating increasing cardiovascular dysfunction. A non-surviving participant receives a score of 4 (worst score) for the day of death and every day thereafter.
- Average Respiratory Sequential Organ Failure Assessment (SOFA) Score Day 1 Through Day 28 [Day 1 through Day 28]
Scores range from 0 (normal) to 4 (organ failure) with an increasing score indicating increasing respiratory dysfunction. A non-surviving participant receives a score of 4 (worst score) for the day of death and every day thereafter.
- Average Renal Sequential Organ Failure Assessment (SOFA) Score Day 1 Through Day 28 [Day 1 through Day 28]
Scores range from 0 (normal) to 4 (organ failure) with an increasing score indicating increasing renal dysfunction. A non-surviving participant receives a score of 4 (worst score) for the day of death and every day thereafter.
- 90-Day Mortality [Day 90]
Expressed as percentage of participants who died from any cause at Day 90 endpoint.
- 180-Day Mortality [Day 180]
Expressed as percentage of participants who died from any cause at Day 180 endpoint.
- Median Survival Time [Day 180]
- EuroQoL Questionnaire-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Scores at Baseline, Days 28, 90 and 180 [Baseline and Days 28 and 90 and 180]
EQ-5D VAS assesses caregiver's impression of participant's overall health state. Scores range from 0 (worst health state) to 100 (best health state), with higher scores indicating a better health state.
- EuroQoL Questionnaire-5 Dimensions (EQ-5D) Total Scores at Baseline, Days 28, 90 and 180 [Baseline and Days 28 and 90 and 180]
The EQ-5D is used to assess participant's overall health. Consists of 5 items: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each item has 3 severity levels (no, some, severe problems). Calculated from EQ-5D, total scores (United States [US] Index Score) range from 0 (worst quality of life) to 1.00 (best quality of life).
- Quality of Life Short Form-12 (SF-12) Scores at Baseline, Days 28, 90 and 180 [Baseline and Days 28 and 90 and 180]
SF-12 was used as an instrument to measure participants' physical wellbeing (physical component) and mental wellbeing (mental component). Scores for each component range from 0-100, with 0= lowest wellbeing, and 100=highest wellbeing.
- Percentage of Participants Discontinued Due to Adverse Events Any Time From Baseline Through Day 28 Endpoint [Baseline through Day 28]
Other Outcome Measures
- Percentage of Participants With Serious Bleeding Events Within System Organ Class Any Time From Baseline Through Day 28 [Baseline through Day 28]
Percentage of participants who experienced serious bleeding events are reported by System Organ Class (SOC) term based on MedDRA 14.0. For a bleeding to qualify as a serious event, it would have to meet the standard definition of a serious adverse event or be a central nervous system bleeding or a bleeding event that lead to administration of ≥3 units packed red blood cells/day for 2 consecutive days.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Must be 18 years or older
-
Must have evidence of infection
-
Must have systemic inflammatory response syndrome (SIRS)
-
Must have vasopressor-dependent septic shock
Exclusion Criteria:
-
Have received vasopressor therapy (at any dose) for greater than 24 hours prior to the start of study drug
-
Have sepsis-induced organ dysfunction for greater than 36 hours prior to the start of the study drug infusion
-
Have single organ dysfunction and recent surgery (within 30 days of study entry)
-
Have had surgery performed within the 12-hour period immediately preceding the study drug infusion, or are postoperative with evidence of active bleeding, or have planned or anticipated surgery during the infusion period
-
Are not expected to survive 28 days given their preexisting uncorrectable medical condition
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 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. | Birmingham | Alabama | United States | 35294 |
| 2 | 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. | Loma Linda | California | United States | 92350 |
| 3 | 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. | Long Beach | California | United States | 90806 |
| 4 | 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. | San Diego | California | United States | 92123 |
| 5 | 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. | Colorado Springs | Colorado | United States | 80920 |
| 6 | 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. | Denver | Colorado | United States | 80204 |
| 7 | 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. | Idaho Falls | Idaho | United States | 83404 |
| 8 | 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. | Chicago | Illinois | United States | 60611 |
| 9 | 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. | Iowa City | Iowa | United States | 52242 |
| 10 | 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. | Topeka | Kansas | United States | 66604 |
| 11 | 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. | Hazard | Kentucky | United States | 41701 |
| 12 | 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. | Lansing | Michigan | United States | 48912 |
| 13 | 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. | Chesterfield | Missouri | United States | 63017 |
| 14 | 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. | St Louis | Missouri | United States | 63131 |
| 15 | 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. | Missoula | Montana | United States | 59802 |
| 16 | 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. | Brooklyn | New York | United States | 11215 |
| 17 | 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. | Staten Island | New York | United States | 10305 |
| 18 | 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. | Greensboro | North Carolina | United States | 27403 |
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| 22 | 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. | San Antonio | Texas | United States | 78229 |
| 23 | 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. | Norfolk | Virginia | United States | 23507 |
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| 63 | 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. | Usti Nad Labem | Czech Republic | 40113 | |
| 64 | 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. | Helsinki | Finland | 00029 | |
| 65 | 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. | Jyvaskyla | Finland | 40620 | |
| 66 | 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. | Kuopio | Finland | 70211 | |
| 67 | 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. | Lahti | Finland | 15850 | |
| 68 | 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. | Seinajoki | Finland | 60220 | |
| 69 | 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. | Tampere | Finland | 33520 | |
| 70 | 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. | Angers | France | 49933 | |
| 71 | 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. | Argenteuil | France | 95107 | |
| 72 | 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. | Bobigny | France | 93009 | |
| 73 | 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. | Bordeaux | France | 33076 | |
| 74 | 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. | Dijon | France | 21079 | |
| 75 | 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. | La Roche Sur Yon | France | 85000 | |
| 76 | 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. | Le Kremlin Bicetre | France | 94275 | |
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| 135 | 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. | Tortosa | Spain | 43500 | |
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| 148 | 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. | Birmingham | West Midlands | United Kingdom | B15 2TH |
| 149 | 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. | Chichester | West Sussex | United Kingdom | PO19 6SE |
| 150 | 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. | London | United Kingdom | SW17 0QY |
Sponsors and Collaborators
- Eli Lilly and Company
Investigators
- Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00604214
Other Study ID Numbers:
- 11940
- F1K-MC-EVDP
First Posted:
Jan 30, 2008
Last Update Posted:
Sep 18, 2012
Last Verified:
Aug 1, 2012
Keywords provided by Eli Lilly and Company
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Drotrecogin Alfa (Activated) | Placebo |
|---|---|---|
| Arm/Group Description | 24 microgram/kilogram/hour, intravenous, 96 hours | 0.9% sodium chloride, intravenous, 96 hours |
| Period Title: Baseline to Day 28 | ||
| STARTED | 851 | 845 |
| Received Study Drug | 833 | 833 |
| COMPLETED | 623 | 632 |
| NOT COMPLETED | 228 | 213 |
| Period Title: Baseline to Day 28 | ||
| STARTED | 623 | 632 |
| COMPLETED | 555 | 553 |
| NOT COMPLETED | 68 | 79 |
| Period Title: Baseline to Day 28 | ||
| STARTED | 555 | 553 |
| COMPLETED | 529 | 521 |
| NOT COMPLETED | 26 | 32 |
Baseline Characteristics
| Arm/Group Title | Drotrecogin Alfa (Activated) | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | 24 microgram/kilogram/hour, intravenous, 96 hours | 0.9% sodium chloride, intravenous, 96 hours | Total of all reporting groups |
| Overall Participants | 851 | 845 | 1696 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
63.42
(15.42)
|
62.70
(16.41)
|
63.06
(15.92)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
360
42.3%
|
379
44.9%
|
739
43.6%
|
| Male |
491
57.7%
|
466
55.1%
|
957
56.4%
|
| Race/Ethnicity, Customized (participants) [Number] | |||
| Aboriginal/Torres Strait Islander |
2
0.2%
|
6
0.7%
|
8
0.5%
|
| African |
30
3.5%
|
27
3.2%
|
57
3.4%
|
| Caucasian |
740
87%
|
721
85.3%
|
1461
86.1%
|
| East Asian/Pacific |
21
2.5%
|
10
1.2%
|
31
1.8%
|
| Hispanic |
21
2.5%
|
32
3.8%
|
53
3.1%
|
| Native American |
3
0.4%
|
4
0.5%
|
7
0.4%
|
| West Asian (Indian Subcontinent) |
34
4%
|
45
5.3%
|
79
4.7%
|
| Region of Enrollment (participants) [Number] | |||
| Portugal |
3
0.4%
|
5
0.6%
|
8
0.5%
|
| United States |
78
9.2%
|
82
9.7%
|
160
9.4%
|
| Finland |
45
5.3%
|
42
5%
|
87
5.1%
|
| Spain |
87
10.2%
|
84
9.9%
|
171
10.1%
|
| Switzerland |
8
0.9%
|
10
1.2%
|
18
1.1%
|
| United Kingdom |
44
5.2%
|
49
5.8%
|
93
5.5%
|
| Italy |
54
6.3%
|
53
6.3%
|
107
6.3%
|
| India |
40
4.7%
|
41
4.9%
|
81
4.8%
|
| France |
235
27.6%
|
229
27.1%
|
464
27.4%
|
| Czech Republic |
30
3.5%
|
24
2.8%
|
54
3.2%
|
| Mexico |
7
0.8%
|
7
0.8%
|
14
0.8%
|
| Canada |
36
4.2%
|
43
5.1%
|
79
4.7%
|
| Brazil |
18
2.1%
|
18
2.1%
|
36
2.1%
|
| Belgium |
69
8.1%
|
70
8.3%
|
139
8.2%
|
| Australia |
36
4.2%
|
28
3.3%
|
64
3.8%
|
| Netherlands |
15
1.8%
|
15
1.8%
|
30
1.8%
|
| Germany |
22
2.6%
|
23
2.7%
|
45
2.7%
|
| New Zealand |
24
2.8%
|
22
2.6%
|
46
2.7%
|
| Primary Site of Infection (participants) [Number] | |||
| Abdomen |
263
30.9%
|
246
29.1%
|
509
30%
|
| Blood |
40
4.7%
|
25
3%
|
65
3.8%
|
| Bone |
2
0.2%
|
2
0.2%
|
4
0.2%
|
| Central Nervous System |
11
1.3%
|
9
1.1%
|
20
1.2%
|
| Head |
2
0.2%
|
3
0.4%
|
5
0.3%
|
| Heart |
3
0.4%
|
3
0.4%
|
6
0.4%
|
| Lung |
369
43.4%
|
375
44.4%
|
744
43.9%
|
| Other |
11
1.3%
|
17
2%
|
28
1.7%
|
| Pleura |
2
0.2%
|
5
0.6%
|
7
0.4%
|
| Reproductive Tract |
2
0.2%
|
2
0.2%
|
4
0.2%
|
| Skin or Skin Structure |
48
5.6%
|
45
5.3%
|
93
5.5%
|
| Urinary Tract |
97
11.4%
|
112
13.3%
|
209
12.3%
|
| Unknown |
1
0.1%
|
1
0.1%
|
2
0.1%
|
| Cardiovascular Sequential Organ Failure Assessment (SOFA) Score (units on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [units on a scale] |
3.91
(0.32)
|
3.89
(0.35)
|
3.90
(0.33)
|
| Respiratory Sequential Organ Failure Assessment (SOFA) Score (units on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [units on a scale] |
2.78
(1.07)
|
2.74
(1.08)
|
2.76
(1.08)
|
| Renal Sequential Organ Failure Assessment (SOFA) Score (units on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [units on a scale] |
1.67
(1.33)
|
1.60
(1.34)
|
1.63
(1.33)
|
| Coagulation Sequential Organ Failure Assessment (SOFA) Score (units on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [units on a scale] |
0.76
(0.97)
|
0.71
(0.96)
|
0.74
(0.96)
|
| Liver Sequential Organ Failure Assessment (SOFA) Score (units on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [units on a scale] |
0.55
(0.85)
|
0.53
(0.88)
|
0.54
(0.87)
|
| Acute Physiology and Chronic Health Evaluation II (APACHE II) Score (units on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [units on a scale] |
25.17
(8.06)
|
25.45
(8.14)
|
25.31
(8.10)
|
Outcome Measures
| Title | 28-Day All-Cause Mortality |
|---|---|
| Description | Expressed as percentage of participants who died from any cause at Day 28 endpoint. |
| Time Frame | Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants with known mortality status at Day 28. |
| Arm/Group Title | Drotrecogin Alfa (Activated) | Placebo |
|---|---|---|
| Arm/Group Description | 24 microgram/kilogram/hour, intravenous, 96 hours | 0.9% sodium chloride, intravenous, 96 hours |
| Measure Participants | 846 | 834 |
| Number [percentage of participants] |
26.4
3.1%
|
24.2
2.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Drotrecogin Alfa (Activated), Placebo |
|---|---|---|
| Comments | The study was planned to have 80% power to detect a 20% relative risk reduction in 28-day all-cause mortality in drotrecogin alpha (activated) compared to placebo. The final power was 75% because of the lower than anticipated placebo mortality. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.313 |
| Comments | No adjustment for multiple comparisons. | |
| Method | Chi-squared | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 1.088 | |
| Confidence Interval |
(2-Sided) 95% 0.923 to 1.283 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | 28-Day All-Cause Mortality in Participants With Severe Protein C Deficiency |
|---|---|
| Description | Expressed as percentage of participants who died from any cause at Day 28 endpoint. Participants with severe protein C deficiency are those who had a protein C level ≤ half the lower limit of normal (LLN) (≤40%). |
| Time Frame | Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants with severe protein C deficiency at Baseline with known mortality status at Day 28. |
| Arm/Group Title | Drotrecogin Alfa (Activated) | Placebo |
|---|---|---|
| Arm/Group Description | 24 microgram/kilogram/hour, intravenous, 96 hours | 0.9% sodium chloride, intravenous, 96 hours |
| Measure Participants | 342 | 331 |
| Number [percentage of participants] |
28.7
3.4%
|
30.8
3.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Drotrecogin Alfa (Activated), Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.540 |
| Comments | No adjustments for multiple comparisons. | |
| Method | Chi-squared | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.930 | |
| Confidence Interval |
(2-Sided) 95% 0.737 to 1.173 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Average Cardiovascular Sequential Organ Failure Assessment (SOFA) Score Day 1 Through Day 28 |
|---|---|
| Description | Scores range from 0 (normal) to 4 (organ failure) with an increasing score indicating increasing cardiovascular dysfunction. A non-surviving participant receives a score of 4 (worst score) for the day of death and every day thereafter. |
| Time Frame | Day 1 through Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants with any post-baseline data on Day 1 through Day 28. For those days when a participant is alive, but no data are available, last observation carried forward (LOFC) is used to impute the missing data. A non-surviving participant receives a score of 4 (worst score) for the day of death and every day thereafter. |
| Arm/Group Title | Drotrecogin Alfa (Activated) | Placebo |
|---|---|---|
| Arm/Group Description | 24 microgram/kilogram/hour, intravenous, 96 hours | 0.9% sodium chloride, intravenous, 96 hours |
| Measure Participants | 837 | 828 |
| Mean (Standard Deviation) [units on a scale] |
1.92
(1.31)
|
1.84
(1.31)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Drotrecogin Alfa (Activated), Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.181 |
| Comments | No adjustments for multiple comparisons. | |
| Method | ANOVA | |
| Comments | ||
| Title | Average Respiratory Sequential Organ Failure Assessment (SOFA) Score Day 1 Through Day 28 |
|---|---|
| Description | Scores range from 0 (normal) to 4 (organ failure) with an increasing score indicating increasing respiratory dysfunction. A non-surviving participant receives a score of 4 (worst score) for the day of death and every day thereafter. |
| Time Frame | Day 1 through Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants with any post-baseline data on Day 1 through Day 28. For those days when a participant is alive, but no data are available, last observation carried forward (LOFC) is used to impute the missing data. A non-surviving participant receives a score of 4 (worst score) for the day of death and every day thereafter. |
| Arm/Group Title | Drotrecogin Alfa (Activated) | Placebo |
|---|---|---|
| Arm/Group Description | 24 microgram/kilogram/hour, intravenous, 96 hours | 0.9% sodium chloride, intravenous, 96 hours |
| Measure Participants | 817 | 806 |
| Mean (Standard Deviation) [units on a scale] |
2.31
(1.05)
|
2.29
(1.05)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Drotrecogin Alfa (Activated), Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.733 |
| Comments | No adjustments for multiple comparisons. | |
| Method | ANOVA | |
| Comments | ||
| Title | Average Renal Sequential Organ Failure Assessment (SOFA) Score Day 1 Through Day 28 |
|---|---|
| Description | Scores range from 0 (normal) to 4 (organ failure) with an increasing score indicating increasing renal dysfunction. A non-surviving participant receives a score of 4 (worst score) for the day of death and every day thereafter. |
| Time Frame | Day 1 through Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants with any post-baseline data on Day 1 through Day 28. For those days when a participant is alive, but no data are available, last observation carried forward (LOFC) is used to impute the missing data. A non-surviving participant receives a score of 4 (worst score) for the day of death and every day thereafter. |
| Arm/Group Title | Drotrecogin Alfa (Activated) | Placebo |
|---|---|---|
| Arm/Group Description | 24 microgram/kilogram/hour, intravenous, 96 hours | 0.9% sodium chloride, intravenous, 96 hours |
| Measure Participants | 836 | 827 |
| Mean (Standard Deviation) [units on a scale] |
1.38
(1.42)
|
1.28
(1.40)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Drotrecogin Alfa (Activated), Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.122 |
| Comments | No adjustments for multiple comparisons. | |
| Method | ANOVA | |
| Comments | ||
| Title | 90-Day Mortality |
|---|---|
| Description | Expressed as percentage of participants who died from any cause at Day 90 endpoint. |
| Time Frame | Day 90 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants with known mortality status at Day 90. |
| Arm/Group Title | Drotrecogin Alfa (Activated) | Placebo |
|---|---|---|
| Arm/Group Description | 24 microgram/kilogram/hour, intravenous, 96 hours | 0.9% sodium chloride, intravenous, 96 hours |
| Measure Participants | 842 | 822 |
| Number [percentage of participants] |
34.1
4%
|
32.7
3.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Drotrecogin Alfa (Activated), Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.556 |
| Comments | No adjustments for multiple comparisons. | |
| Method | Chi-squared | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 1.042 | |
| Confidence Interval |
(2-Sided) 95% 0.909 to 1.193 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | 180-Day Mortality |
|---|---|
| Description | Expressed as percentage of participants who died from any cause at Day 180 endpoint. |
| Time Frame | Day 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants with known mortality status at Day 180. |
| Arm/Group Title | Drotrecogin Alfa (Activated) | Placebo |
|---|---|---|
| Arm/Group Description | 24 microgram/kilogram/hour, intravenous, 96 hours | 0.9% sodium chloride, intravenous, 96 hours |
| Measure Participants | 835 | 813 |
| Number [percentage of participants] |
36.6
4.3%
|
35.9
4.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Drotrecogin Alfa (Activated), Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.758 |
| Comments | No adjustments for multiple comparisons. | |
| Method | Chi-squared | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 1.020 | |
| Confidence Interval |
(2-Sided) 95% 0.898 to 1.160 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Median Survival Time |
|---|---|
| Description | |
| Time Frame | Day 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants excluding those with unknown mortality status at Day 180. |
| Arm/Group Title | Drotrecogin Alfa (Activated) | Placebo |
|---|---|---|
| Arm/Group Description | 24 microgram/kilogram/hour, intravenous, 96 hours | 0.9% sodium chloride, intravenous, 96 hours |
| Measure Participants | 835 | 813 |
| Median (Full Range) [days] |
NA
|
NA
|
| Title | EuroQoL Questionnaire-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Scores at Baseline, Days 28, 90 and 180 |
|---|---|
| Description | EQ-5D VAS assesses caregiver's impression of participant's overall health state. Scores range from 0 (worst health state) to 100 (best health state), with higher scores indicating a better health state. |
| Time Frame | Baseline and Days 28 and 90 and 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants with EQ-5D VAS data at the specified time points. |
| Arm/Group Title | Drotrecogin Alfa (Activated) | Placebo |
|---|---|---|
| Arm/Group Description | 24 microgram/kilogram/hour, intravenous, 96 hours | 0.9% sodium chloride, intravenous, 96 hours |
| Measure Participants | 851 | 845 |
| Baseline (n=685, 679) |
54.21
(26.99)
|
54.37
(27.95)
|
| Day 28 (n=500, 476) |
54.78
(23.46)
|
55.24
(22.89)
|
| Day 90 (n=474, 469) |
64.41
(21.00)
|
65.18
(20.15)
|
| Day 180 (n=456, 443) |
68.94
(20.19)
|
69.08
(20.50)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Drotrecogin Alfa (Activated), Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.788 |
| Comments | P-value is for Baseline, unadjusted for multiple comparisons. | |
| Method | ANOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Drotrecogin Alfa (Activated), Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.730 |
| Comments | P-value is for Day 28, unadjusted for multiple comparisons. | |
| Method | ANOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Drotrecogin Alfa (Activated), Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.662 |
| Comments | P-value is for Day 90, unadjusted for multiple comparisons. | |
| Method | ANOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Drotrecogin Alfa (Activated), Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.846 |
| Comments | P-value is for Day 180, unadjusted for multiple comparisons. | |
| Method | ANOVA | |
| Comments | ||
| Title | EuroQoL Questionnaire-5 Dimensions (EQ-5D) Total Scores at Baseline, Days 28, 90 and 180 |
|---|---|
| Description | The EQ-5D is used to assess participant's overall health. Consists of 5 items: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each item has 3 severity levels (no, some, severe problems). Calculated from EQ-5D, total scores (United States [US] Index Score) range from 0 (worst quality of life) to 1.00 (best quality of life). |
| Time Frame | Baseline and Days 28 and 90 and 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants with EQ-5D total score data at the specified time points. |
| Arm/Group Title | Drotrecogin Alfa (Activated) | Placebo |
|---|---|---|
| Arm/Group Description | 24 microgram/kilogram/hour, intravenous, 96 hours | 0.9% sodium chloride, intravenous, 96 hours |
| Measure Participants | 851 | 845 |
| Baseline (n=702, 705) |
0.60
(0.35)
|
0.60
(0.35)
|
| Day 28 (n=509, 486) |
0.51
(0.33)
|
0.53
(0.33)
|
| Day 90 (n=480, 473) |
0.71
(0.27)
|
0.71
(0.28)
|
| Day 180 (n=458, 448) |
0.77
(0.23)
|
0.76
(0.25)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Drotrecogin Alfa (Activated), Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.697 |
| Comments | P-value is for Baseline, unadjusted for multiple comparisons. | |
| Method | ANOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Drotrecogin Alfa (Activated), Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.306 |
| Comments | P-value is for Day 28, unadjusted for multiple comparisons. | |
| Method | ANOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Drotrecogin Alfa (Activated), Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.645 |
| Comments | P-value is for Day 90, unadjusted for multiple comparisons. | |
| Method | ANOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Drotrecogin Alfa (Activated), Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.690 |
| Comments | P-value is for Day 180, unadjusted for multiple comparisons. | |
| Method | ANOVA | |
| Comments | ||
| Title | Quality of Life Short Form-12 (SF-12) Scores at Baseline, Days 28, 90 and 180 |
|---|---|
| Description | SF-12 was used as an instrument to measure participants' physical wellbeing (physical component) and mental wellbeing (mental component). Scores for each component range from 0-100, with 0= lowest wellbeing, and 100=highest wellbeing. |
| Time Frame | Baseline and Days 28 and 90 and 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants with SF-12 score data at the specified time points. |
| Arm/Group Title | Drotrecogin Alfa (Activated) | Placebo |
|---|---|---|
| Arm/Group Description | 24 microgram/kilogram/hour, intravenous, 96 hours | 0.9% sodium chloride, intravenous, 96 hours |
| Measure Participants | 851 | 845 |
| Physical Component at Baseline (n=683, 696) |
39.14
(12.04)
|
39.22
(12.10)
|
| Physical Component at Day 28 (n=484, 465) |
31.14
(10.29)
|
31.13
(9.84)
|
| Physical Component at Day 90 (n=474, 459) |
38.09
(11.17)
|
40.03
(11.23)
|
| Physical Component at Day 180 (n=450, 444) |
42.26
(10.80)
|
41.59
(11.28)
|
| Mental Component at Baseline (n=683, 696) |
45.44
(13.07)
|
46.03
(12.88)
|
| Mental Component at Day 28 (n=484, 465) |
40.57
(13.12)
|
41.45
(12.59)
|
| Mental Component at Day 90 (n=474, 459) |
47.53
(12.08)
|
48.52
(12.36)
|
| Mental Component at Day 180 (n=450, 444) |
50.42
(11.50)
|
50.55
(11.70)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Drotrecogin Alfa (Activated), Placebo |
|---|---|---|
| Comments | Analysis on ranked data. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.482 |
| Comments | P-value is for physical component at Baseline, unadjusted for multiple comparisons. | |
| Method | ANOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Drotrecogin Alfa (Activated), Placebo |
|---|---|---|
| Comments | Analysis on ranked data. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.584 |
| Comments | P-value is for physical component at Day 28, unadjusted for multiple comparisons. | |
| Method | ANOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Drotrecogin Alfa (Activated), Placebo |
|---|---|---|
| Comments | Analysis on ranked data. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.164 |
| Comments | P-value is for physical component at Day 90, unadjusted for multiple comparisons. | |
| Method | ANOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Drotrecogin Alfa (Activated), Placebo |
|---|---|---|
| Comments | Analysis on ranked data. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.666 |
| Comments | P-value is for physical component at Day 180, unadjusted for multiple comparisons. | |
| Method | ANOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Drotrecogin Alfa (Activated), Placebo |
|---|---|---|
| Comments | Analysis on ranked data. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.786 |
| Comments | P-value is for mental component at Baseline, unadjusted for multiple comparisons. | |
| Method | ANOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Drotrecogin Alfa (Activated), Placebo |
|---|---|---|
| Comments | Analysis on ranked data. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.160 |
| Comments | P-value is for mental component at Day 28, unadjusted for multiple comparisons. | |
| Method | ANOVA | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Drotrecogin Alfa (Activated), Placebo |
|---|---|---|
| Comments | Analysis on ranked data. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.696 |
| Comments | P-value is for mental component at Day 90, unadjusted for multiple comparisons. | |
| Method | ANOVA | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Drotrecogin Alfa (Activated), Placebo |
|---|---|---|
| Comments | Analysis on ranked data. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.966 |
| Comments | P-value is for mental component at Day 180, unadjusted for multiple comparisons. | |
| Method | ANOVA | |
| Comments | ||
| Title | Percentage of Participants With Serious Bleeding Events Within System Organ Class Any Time From Baseline Through Day 28 |
|---|---|
| Description | Percentage of participants who experienced serious bleeding events are reported by System Organ Class (SOC) term based on MedDRA 14.0. For a bleeding to qualify as a serious event, it would have to meet the standard definition of a serious adverse event or be a central nervous system bleeding or a bleeding event that lead to administration of ≥3 units packed red blood cells/day for 2 consecutive days. |
| Time Frame | Baseline through Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received study drug. |
| Arm/Group Title | Drotrecogin Alfa (Activated) | Placebo |
|---|---|---|
| Arm/Group Description | 24 microgram/kilogram/hour, intravenous, 96 hours | 0.9% sodium chloride, intravenous, 96 hours |
| Measure Participants | 833 | 833 |
| with ≥1 event |
2.4
0.3%
|
2.8
0.3%
|
| Gastrointestinal Disorders |
1.1
0.1%
|
0.7
0.1%
|
| Injury, Poisoning And Procedural Complications |
0
0%
|
0.6
0.1%
|
| Nervous System Disorders |
0.4
0%
|
0.4
0%
|
| Renal And Urinary Disorders |
0.1
0%
|
0
0%
|
| Respiratory, Thoracic And Mediastinal Disorders |
0.4
0%
|
0.4
0%
|
| Vascular Disorders |
0.5
0.1%
|
1.0
0.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Drotrecogin Alfa (Activated), Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.758 |
| Comments | P-value is for participants with ≥1 event. No adjustments for multiple comparisons. | |
| Method | Fisher Exact | |
| Comments | ||
| Title | Percentage of Participants Discontinued Due to Adverse Events Any Time From Baseline Through Day 28 Endpoint |
|---|---|
| Description | |
| Time Frame | Baseline through Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received study drug. |
| Arm/Group Title | Drotrecogin Alfa (Activated) | Placebo |
|---|---|---|
| Arm/Group Description | 24 microgram/kilogram/hour, intravenous, 96 hours | 0.9% sodium chloride, intravenous, 96 hours |
| Measure Participants | 833 | 833 |
| Number [percentage of participants] |
4.4
0.5%
|
3.0
0.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Drotrecogin Alfa (Activated), Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.154 |
| Comments | Unadjusted for multiple comparisons. | |
| Method | Fisher Exact | |
| Comments | ||
Adverse Events
| Time Frame | Day 0 to Day 28 | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Drotrecogin Alfa (Activated) | Placebo | ||
| Arm/Group Description | 24 microgram/kilogram/hour, intravenous, 96 hours | 0.9% sodium chloride, intravenous, 96 hours | ||
All Cause Mortality |
||||
| Drotrecogin Alfa (Activated) | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Drotrecogin Alfa (Activated) | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 119/833 (14.3%) | 96/833 (11.5%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 2/833 (0.2%) | 4 | 2/833 (0.2%) | 3 |
| Coagulopathy | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Cardiac disorders | ||||
| Acute myocardial infarction | 3/833 (0.4%) | 6 | 1/833 (0.1%) | 2 |
| Arrhythmia | 1/833 (0.1%) | 1 | 1/833 (0.1%) | 1 |
| Atrial fibrillation | 1/833 (0.1%) | 1 | 2/833 (0.2%) | 2 |
| Bradycardia | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Cardiac arrest | 13/833 (1.6%) | 15 | 8/833 (1%) | 8 |
| Cardiac failure | 0/833 (0%) | 0 | 2/833 (0.2%) | 2 |
| Cardio-respiratory arrest | 1/833 (0.1%) | 1 | 2/833 (0.2%) | 2 |
| Cardiogenic shock | 0/833 (0%) | 0 | 2/833 (0.2%) | 2 |
| Myocardial infarction | 4/833 (0.5%) | 5 | 1/833 (0.1%) | 1 |
| Pulseless electrical activity | 2/833 (0.2%) | 2 | 2/833 (0.2%) | 2 |
| Sick sinus syndrome | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Supraventricular tachyarrhythmia | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Ventricular fibrillation | 3/833 (0.4%) | 4 | 0/833 (0%) | 0 |
| Ventricular tachycardia | 1/833 (0.1%) | 1 | 2/833 (0.2%) | 2 |
| Eye disorders | ||||
| Pupils unequal | 0/833 (0%) | 0 | 1/833 (0.1%) | 2 |
| Gastrointestinal disorders | ||||
| Abdominal discomfort | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Colitis ischaemic | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Duodenal ulcer perforation | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Gastric ulcer haemorrhage | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Gastric ulcer perforation | 0/833 (0%) | 0 | 1/833 (0.1%) | 2 |
| Gastrointestinal haemorrhage | 6/833 (0.7%) | 6 | 3/833 (0.4%) | 5 |
| Gastrointestinal ischaemia | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Gastrointestinal necrosis | 2/833 (0.2%) | 2 | 2/833 (0.2%) | 2 |
| Haematochezia | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Intestinal haemorrhage | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Intestinal ischaemia | 3/833 (0.4%) | 4 | 1/833 (0.1%) | 2 |
| Intestinal obstruction | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Intestinal perforation | 0/833 (0%) | 0 | 1/833 (0.1%) | 2 |
| Large intestine perforation | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Localised intraabdominal fluid collection | 1/833 (0.1%) | 3 | 0/833 (0%) | 0 |
| Melaena | 1/833 (0.1%) | 2 | 0/833 (0%) | 0 |
| Peritoneal haematoma | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Peritonitis | 2/833 (0.2%) | 3 | 2/833 (0.2%) | 2 |
| Rectal perforation | 1/833 (0.1%) | 2 | 0/833 (0%) | 0 |
| Retroperitoneal haemorrhage | 1/833 (0.1%) | 2 | 0/833 (0%) | 0 |
| Sigmoiditis | 0/833 (0%) | 0 | 1/833 (0.1%) | 2 |
| Volvulus | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| General disorders | ||||
| Brain death | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Death | 1/833 (0.1%) | 1 | 2/833 (0.2%) | 2 |
| Device dislocation | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| General physical health deterioration | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Idiosyncratic drug reaction | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Hepatobiliary disorders | ||||
| Hepatic cirrhosis | 1/833 (0.1%) | 3 | 0/833 (0%) | 0 |
| Infections and infestations | ||||
| Abdominal abscess | 3/833 (0.4%) | 7 | 1/833 (0.1%) | 1 |
| Abdominal wall abscess | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Bronchopneumonia | 1/833 (0.1%) | 2 | 0/833 (0%) | 0 |
| Cholecystitis infective | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Clostridium difficile colitis | 1/833 (0.1%) | 2 | 0/833 (0%) | 0 |
| Colon gangrene | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Device related sepsis | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Diabetic gangrene | 0/833 (0%) | 0 | 1/833 (0.1%) | 2 |
| Enterobacter sepsis | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Infection | 1/833 (0.1%) | 2 | 0/833 (0%) | 0 |
| Meningitis pneumococcal | 1/833 (0.1%) | 2 | 0/833 (0%) | 0 |
| Periorbital cellulitis | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Pneumonia | 5/833 (0.6%) | 10 | 3/833 (0.4%) | 3 |
| Pneumonia necrotising | 0/833 (0%) | 0 | 1/833 (0.1%) | 2 |
| Pneumonia staphylococcal | 2/833 (0.2%) | 3 | 0/833 (0%) | 0 |
| Postoperative wound infection | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Pyelonephritis | 0/833 (0%) | 0 | 1/833 (0.1%) | 2 |
| Septic shock | 2/833 (0.2%) | 2 | 1/833 (0.1%) | 1 |
| Subcutaneous abscess | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Superinfection bacterial | 1/833 (0.1%) | 3 | 0/833 (0%) | 0 |
| Systemic candida | 0/833 (0%) | 0 | 1/833 (0.1%) | 2 |
| Urinary tract infection | 0/833 (0%) | 0 | 1/833 (0.1%) | 2 |
| Urosepsis | 4/833 (0.5%) | 6 | 2/833 (0.2%) | 5 |
| Injury, poisoning and procedural complications | ||||
| Abdominal wound dehiscence | 1/833 (0.1%) | 1 | 1/833 (0.1%) | 1 |
| Anastomotic fistula | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Arteriovenous fistula site haemorrhage | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Biliary anastomosis complication | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Endotracheal intubation complication | 0/833 (0%) | 0 | 1/833 (0.1%) | 2 |
| Gastrointestinal anastomotic leak | 2/833 (0.2%) | 4 | 0/833 (0%) | 0 |
| Gastrointestinal stoma necrosis | 1/833 (0.1%) | 2 | 0/833 (0%) | 0 |
| Hip fracture | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Incision site haemorrhage | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Suture rupture | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Toxicity to various agents | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Tracheal haemorrhage | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Wound dehiscence | 1/833 (0.1%) | 5 | 2/833 (0.2%) | 3 |
| Wound haemorrhage | 0/833 (0%) | 0 | 2/833 (0.2%) | 4 |
| Investigations | ||||
| Oxygen saturation decreased | 1/833 (0.1%) | 2 | 0/833 (0%) | 0 |
| Pulse absent | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Metabolism and nutrition disorders | ||||
| Fluid overload | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Hypoglycaemia | 1/833 (0.1%) | 1 | 1/833 (0.1%) | 2 |
| Hypoglycaemic seizure | 0/833 (0%) | 0 | 1/833 (0.1%) | 3 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Brain neoplasm malignant | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Lung neoplasm | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Lymphoproliferative disorder | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Mucoepidermoid carcinoma | 1/833 (0.1%) | 2 | 0/833 (0%) | 0 |
| Multiple myeloma | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Neoplasm progression | 1/833 (0.1%) | 1 | 1/833 (0.1%) | 1 |
| Rectal cancer | 0/833 (0%) | 0 | 1/833 (0.1%) | 2 |
| Nervous system disorders | ||||
| Cerebral artery embolism | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Cerebral haematoma | 0/833 (0%) | 0 | 2/833 (0.2%) | 3 |
| Cerebral haemorrhage | 2/833 (0.2%) | 4 | 0/833 (0%) | 0 |
| Cerebral infarction | 1/833 (0.1%) | 1 | 1/833 (0.1%) | 4 |
| Cerebral ischaemia | 1/833 (0.1%) | 2 | 0/833 (0%) | 0 |
| Cerebrovascular accident | 1/833 (0.1%) | 4 | 1/833 (0.1%) | 1 |
| Dementia alzheimer's type | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Encephalopathy | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Epilepsy | 2/833 (0.2%) | 3 | 0/833 (0%) | 0 |
| Haemorrhagic stroke | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Ischaemic stroke | 4/833 (0.5%) | 5 | 4/833 (0.5%) | 5 |
| Neuroleptic malignant syndrome | 0/833 (0%) | 0 | 1/833 (0.1%) | 4 |
| Neuropathy peripheral | 0/833 (0%) | 0 | 1/833 (0.1%) | 3 |
| Posterior reversible encephalopathy syndrome | 0/833 (0%) | 0 | 1/833 (0.1%) | 3 |
| Subarachnoid haemorrhage | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Transient ischaemic attack | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Renal and urinary disorders | ||||
| Haematuria | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Renal failure acute | 0/833 (0%) | 0 | 1/833 (0.1%) | 2 |
| Renal infarct | 1/833 (0.1%) | 2 | 0/833 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute respiratory failure | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Aspiration | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Atelectasis | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Bronchial haemorrhage | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Chronic obstructive pulmonary disease | 2/833 (0.2%) | 4 | 1/833 (0.1%) | 1 |
| Haemoptysis | 1/833 (0.1%) | 2 | 1/833 (0.1%) | 1 |
| Haemothorax | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Hypoxia | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Interstitial lung disease | 1/833 (0.1%) | 2 | 0/833 (0%) | 0 |
| Obstructive airways disorder | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Pleural effusion | 2/833 (0.2%) | 3 | 1/833 (0.1%) | 3 |
| Pneumonia aspiration | 2/833 (0.2%) | 2 | 0/833 (0%) | 0 |
| Pneumothorax | 2/833 (0.2%) | 2 | 1/833 (0.1%) | 1 |
| Pulmonary alveolar haemorrhage | 0/833 (0%) | 0 | 1/833 (0.1%) | 2 |
| Pulmonary embolism | 1/833 (0.1%) | 1 | 1/833 (0.1%) | 2 |
| Pulmonary haemorrhage | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Pulmonary oedema | 1/833 (0.1%) | 2 | 1/833 (0.1%) | 2 |
| Respiratory arrest | 1/833 (0.1%) | 1 | 1/833 (0.1%) | 1 |
| Respiratory failure | 6/833 (0.7%) | 6 | 3/833 (0.4%) | 3 |
| Skin and subcutaneous tissue disorders | ||||
| Drug eruption | 0/833 (0%) | 0 | 1/833 (0.1%) | 2 |
| Vascular disorders | ||||
| Air embolism | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Arterial haemorrhage | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Arterial thrombosis limb | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Haematoma | 1/833 (0.1%) | 2 | 1/833 (0.1%) | 3 |
| Haemorrhage | 1/833 (0.1%) | 3 | 1/833 (0.1%) | 1 |
| Hypotension | 2/833 (0.2%) | 2 | 0/833 (0%) | 0 |
| Hypovolaemic shock | 0/833 (0%) | 0 | 2/833 (0.2%) | 2 |
| Intra-abdominal haemorrhage | 2/833 (0.2%) | 2 | 3/833 (0.4%) | 5 |
| Peripheral ischaemia | 2/833 (0.2%) | 4 | 1/833 (0.1%) | 1 |
| Shock haemorrhagic | 1/833 (0.1%) | 1 | 3/833 (0.4%) | 8 |
Other (Not Including Serious) Adverse Events |
||||
| Drotrecogin Alfa (Activated) | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 151/833 (18.1%) | 119/833 (14.3%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 3/833 (0.4%) | 7 | 1/833 (0.1%) | 3 |
| Autoimmune thrombocytopenia | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Coagulopathy | 2/833 (0.2%) | 3 | 0/833 (0%) | 0 |
| Disseminated intravascular coagulation | 2/833 (0.2%) | 3 | 1/833 (0.1%) | 1 |
| Haemorrhagic anaemia | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Splenic infarction | 1/833 (0.1%) | 3 | 0/833 (0%) | 0 |
| Thrombocytopenia | 12/833 (1.4%) | 21 | 9/833 (1.1%) | 17 |
| Cardiac disorders | ||||
| Acute coronary syndrome | 1/833 (0.1%) | 1 | 3/833 (0.4%) | 9 |
| Acute myocardial infarction | 0/833 (0%) | 0 | 3/833 (0.4%) | 4 |
| Arrhythmia supraventricular | 0/833 (0%) | 0 | 1/833 (0.1%) | 2 |
| Atrial fibrillation | 8/833 (1%) | 16 | 5/833 (0.6%) | 9 |
| Atrial thrombosis | 1/833 (0.1%) | 2 | 1/833 (0.1%) | 1 |
| Cardiac failure | 0/833 (0%) | 0 | 2/833 (0.2%) | 3 |
| Myocardial infarction | 0/833 (0%) | 0 | 3/833 (0.4%) | 7 |
| Myocarditis | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Ventricular tachycardia | 1/833 (0.1%) | 1 | 1/833 (0.1%) | 2 |
| Ear and labyrinth disorders | ||||
| Deafness bilateral | 1/833 (0.1%) | 2 | 0/833 (0%) | 0 |
| Ear haemorrhage | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Eye disorders | ||||
| Conjunctival haemorrhage | 4/833 (0.5%) | 10 | 3/833 (0.4%) | 4 |
| Scleral haemorrhage | 1/833 (0.1%) | 3 | 1/833 (0.1%) | 4 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 0/833 (0%) | 0 | 1/833 (0.1%) | 2 |
| Abdominal wall haemorrhage | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Diarrhoea haemorrhagic | 1/833 (0.1%) | 2 | 0/833 (0%) | 0 |
| Gastric haemorrhage | 6/833 (0.7%) | 9 | 2/833 (0.2%) | 2 |
| Gastric ulcer haemorrhage | 0/833 (0%) | 0 | 2/833 (0.2%) | 2 |
| Gastritis | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Gastrointestinal haemorrhage | 3/833 (0.4%) | 4 | 6/833 (0.7%) | 7 |
| Gingival bleeding | 1/833 (0.1%) | 2 | 0/833 (0%) | 0 |
| Haematemesis | 2/833 (0.2%) | 3 | 1/833 (0.1%) | 1 |
| Haematochezia | 3/833 (0.4%) | 3 | 0/833 (0%) | 0 |
| Intestinal haemorrhage | 2/833 (0.2%) | 2 | 1/833 (0.1%) | 1 |
| Intestinal ischaemia | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Large intestinal haemorrhage | 1/833 (0.1%) | 2 | 0/833 (0%) | 0 |
| Lower gastrointestinal haemorrhage | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Melaena | 3/833 (0.4%) | 5 | 6/833 (0.7%) | 7 |
| Mouth haemorrhage | 3/833 (0.4%) | 4 | 1/833 (0.1%) | 1 |
| Nausea | 0/833 (0%) | 0 | 1/833 (0.1%) | 2 |
| Peritonitis | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Rectal haemorrhage | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Rectal ulcer haemorrhage | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Upper gastrointestinal haemorrhage | 2/833 (0.2%) | 2 | 0/833 (0%) | 0 |
| General disorders | ||||
| Bloody discharge | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Catheter site haemorrhage | 9/833 (1.1%) | 9 | 4/833 (0.5%) | 6 |
| Infusion site extravasation | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Injection site haematoma | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Local swelling | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Mucosal haemorrhage | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Vessel puncture site haemorrhage | 1/833 (0.1%) | 1 | 1/833 (0.1%) | 1 |
| Infections and infestations | ||||
| Clostridial infection | 0/833 (0%) | 0 | 1/833 (0.1%) | 4 |
| Endocarditis | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Hepatic haematoma | 1/833 (0.1%) | 2 | 0/833 (0%) | 0 |
| Incision site haemorrhage | 4/833 (0.5%) | 5 | 1/833 (0.1%) | 1 |
| Operative haemorrhage | 1/833 (0.1%) | 2 | 2/833 (0.2%) | 2 |
| Post procedural haematuria | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Post procedural haemorrhage | 8/833 (1%) | 9 | 2/833 (0.2%) | 2 |
| Subcutaneous haematoma | 0/833 (0%) | 0 | 1/833 (0.1%) | 2 |
| Wound evisceration | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Wound haemorrhage | 6/833 (0.7%) | 7 | 1/833 (0.1%) | 1 |
| Investigations | ||||
| Activated partial thromboplastin time prolonged | 11/833 (1.3%) | 18 | 2/833 (0.2%) | 5 |
| Alanine aminotransferase increased | 1/833 (0.1%) | 4 | 0/833 (0%) | 0 |
| Haemoglobin decreased | 2/833 (0.2%) | 2 | 0/833 (0%) | 0 |
| International normalised ratio increased | 2/833 (0.2%) | 2 | 0/833 (0%) | 0 |
| Occult blood positive | 2/833 (0.2%) | 3 | 2/833 (0.2%) | 2 |
| Platelet count decreased | 3/833 (0.4%) | 4 | 1/833 (0.1%) | 1 |
| Prothrombin time prolonged | 2/833 (0.2%) | 5 | 0/833 (0%) | 0 |
| Prothrombin time shortened | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Troponin increased | 0/833 (0%) | 0 | 1/833 (0.1%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||
| Fistula | 1/833 (0.1%) | 3 | 0/833 (0%) | 0 |
| Muscle haemorrhage | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Metastases to central nervous system | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Nervous system disorders | ||||
| Ischaemic stroke | 0/833 (0%) | 0 | 1/833 (0.1%) | 3 |
| Transient ischaemic attack | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Renal and urinary disorders | ||||
| Haematuria | 11/833 (1.3%) | 12 | 9/833 (1.1%) | 18 |
| Renal haemorrhage | 1/833 (0.1%) | 1 | 1/833 (0.1%) | 2 |
| Renal infarct | 1/833 (0.1%) | 3 | 0/833 (0%) | 0 |
| Urinary bladder haemorrhage | 0/833 (0%) | 0 | 1/833 (0.1%) | 3 |
| Reproductive system and breast disorders | ||||
| Menorrhagia | 1/833 (0.1%) | 4 | 0/833 (0%) | 0 |
| Metrorrhagia | 1/833 (0.1%) | 2 | 0/833 (0%) | 0 |
| Scrotal haematocoele | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Vaginal haemorrhage | 0/833 (0%) | 0 | 2/833 (0.2%) | 3 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Bronchial haemorrhage | 0/833 (0%) | 0 | 1/833 (0.1%) | 1 |
| Epistaxis | 6/833 (0.7%) | 7 | 4/833 (0.5%) | 4 |
| Haemoptysis | 6/833 (0.7%) | 6 | 3/833 (0.4%) | 3 |
| Haemothorax | 1/833 (0.1%) | 1 | 1/833 (0.1%) | 1 |
| Pharyngeal haemorrhage | 1/833 (0.1%) | 2 | 1/833 (0.1%) | 1 |
| Pleural effusion | 0/833 (0%) | 0 | 1/833 (0.1%) | 2 |
| Pleural haemorrhage | 0/833 (0%) | 0 | 2/833 (0.2%) | 3 |
| Pneumothorax | 1/833 (0.1%) | 2 | 1/833 (0.1%) | 1 |
| Pulmonary embolism | 2/833 (0.2%) | 2 | 2/833 (0.2%) | 6 |
| Pulmonary haemorrhage | 2/833 (0.2%) | 3 | 0/833 (0%) | 0 |
| Pulmonary oedema | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Respiratory tract haemorrhage | 2/833 (0.2%) | 2 | 1/833 (0.1%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Dermatitis exfoliative | 0/833 (0%) | 0 | 1/833 (0.1%) | 2 |
| Ecchymosis | 0/833 (0%) | 0 | 1/833 (0.1%) | 2 |
| Vascular disorders | ||||
| Arterial thrombosis | 1/833 (0.1%) | 2 | 0/833 (0%) | 0 |
| Arterial thrombosis limb | 1/833 (0.1%) | 2 | 0/833 (0%) | 0 |
| Axillary vein thrombosis | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Deep vein thrombosis | 10/833 (1.2%) | 26 | 5/833 (0.6%) | 17 |
| Haematoma | 1/833 (0.1%) | 1 | 1/833 (0.1%) | 1 |
| Haemorrhage | 2/833 (0.2%) | 2 | 2/833 (0.2%) | 2 |
| Intra-abdominal haematoma | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
| Intra-abdominal haemorrhage | 2/833 (0.2%) | 2 | 0/833 (0%) | 0 |
| Jugular vein thrombosis | 1/833 (0.1%) | 1 | 2/833 (0.2%) | 4 |
| Necrosis ischaemic | 0/833 (0%) | 0 | 1/833 (0.1%) | 3 |
| Phlebitis | 0/833 (0%) | 0 | 1/833 (0.1%) | 3 |
| Subclavian vein thrombosis | 1/833 (0.1%) | 1 | 1/833 (0.1%) | 4 |
| Thrombophlebitis | 1/833 (0.1%) | 1 | 2/833 (0.2%) | 2 |
| Thrombophlebitis superficial | 0/833 (0%) | 0 | 4/833 (0.5%) | 10 |
| Thrombosis | 1/833 (0.1%) | 4 | 3/833 (0.4%) | 6 |
| Vena cava thrombosis | 1/833 (0.1%) | 1 | 1/833 (0.1%) | 4 |
| Venous thrombosis | 0/833 (0%) | 0 | 1/833 (0.1%) | 2 |
| Venous thrombosis limb | 1/833 (0.1%) | 1 | 0/833 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the site 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 from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo. An independent Steering Committee responsible for data analyses and publications did not have an embargo.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Eli Lilly and Company |
| Phone | 800-545-5979 |
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00604214
Other Study ID Numbers:
- 11940
- F1K-MC-EVDP
First Posted:
Jan 30, 2008
Last Update Posted:
Sep 18, 2012
Last Verified:
Aug 1, 2012