Sepsis
Conditions
Keywords
Sepsis, Septic shock
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.
Interventions
24 microgram/kilogram/hour, intravenous, 96 hours (hr)
DRUGPlacebo
0.9% sodium chloride, intravenous, 96 hours
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 28-Day All-Cause Mortality | Day 28 | Expressed as percentage of participants who died from any cause at Day 28 endpoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 | — |
| 180-Day Mortality | Day 180 | Expressed as percentage of participants who died from any cause at Day 180 endpoint. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Australia, Belgium, Brazil, Canada, Czechia, Finland, France, Germany, India, Italy, Mexico, Netherlands, New Zealand, Portugal, Spain, Switzerland, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Drotrecogin Alfa (Activated) 24 microgram/kilogram/hour, intravenous, 96 hours | 851 |
| Placebo 0.9% sodium chloride, intravenous, 96 hours | 845 |
| Total | 1,696 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Baseline to Day 28 | Death | 223 | 202 |
| Baseline to Day 28 | Lost to Follow-up | 2 | 4 |
| Baseline to Day 28 | Withdrawal by Subject | 3 | 7 |
| Day 29 to Day 90 | Death | 64 | 67 |
| Day 29 to Day 90 | Lost to Follow-up | 4 | 6 |
| Day 29 to Day 90 | Withdrawal by Subject | 0 | 6 |
| Day 91 to Day 180 | Death | 19 | 23 |
| Day 91 to Day 180 | Lost to Follow-up | 6 | 8 |
| Day 91 to Day 180 | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Placebo | Drotrecogin Alfa (Activated) |
|---|---|---|---|
| Acute Physiology and Chronic Health Evaluation II (APACHE II) Score | 25.31 units on a scale STANDARD_DEVIATION 8.1 | 25.45 units on a scale STANDARD_DEVIATION 8.14 | 25.17 units on a scale STANDARD_DEVIATION 8.06 |
| Age Continuous | 63.06 years STANDARD_DEVIATION 15.92 | 62.70 years STANDARD_DEVIATION 16.41 | 63.42 years STANDARD_DEVIATION 15.42 |
| Cardiovascular Sequential Organ Failure Assessment (SOFA) Score | 3.90 units on a scale STANDARD_DEVIATION 0.33 | 3.89 units on a scale STANDARD_DEVIATION 0.35 | 3.91 units on a scale STANDARD_DEVIATION 0.32 |
| Coagulation Sequential Organ Failure Assessment (SOFA) Score | 0.74 units on a scale STANDARD_DEVIATION 0.96 | 0.71 units on a scale STANDARD_DEVIATION 0.96 | 0.76 units on a scale STANDARD_DEVIATION 0.97 |
| Liver Sequential Organ Failure Assessment (SOFA) Score | 0.54 units on a scale STANDARD_DEVIATION 0.87 | 0.53 units on a scale STANDARD_DEVIATION 0.88 | 0.55 units on a scale STANDARD_DEVIATION 0.85 |
| Primary Site of Infection Abdomen | 509 participants | 246 participants | 263 participants |
| Primary Site of Infection Blood | 65 participants | 25 participants | 40 participants |
| Primary Site of Infection Bone | 4 participants | 2 participants | 2 participants |
| Primary Site of Infection Central Nervous System | 20 participants | 9 participants | 11 participants |
| Primary Site of Infection Head | 5 participants | 3 participants | 2 participants |
| Primary Site of Infection Heart | 6 participants | 3 participants | 3 participants |
| Primary Site of Infection Lung | 744 participants | 375 participants | 369 participants |
| Primary Site of Infection Other | 28 participants | 17 participants | 11 participants |
| Primary Site of Infection Pleura | 7 participants | 5 participants | 2 participants |
| Primary Site of Infection Reproductive Tract | 4 participants | 2 participants | 2 participants |
| Primary Site of Infection Skin or Skin Structure | 93 participants | 45 participants | 48 participants |
| Primary Site of Infection Unknown | 2 participants | 1 participants | 1 participants |
| Primary Site of Infection Urinary Tract | 209 participants | 112 participants | 97 participants |
| Race/Ethnicity, Customized Aboriginal/Torres Strait Islander | 8 participants | 6 participants | 2 participants |
| Race/Ethnicity, Customized African | 57 participants | 27 participants | 30 participants |
| Race/Ethnicity, Customized Caucasian | 1461 participants | 721 participants | 740 participants |
| Race/Ethnicity, Customized East Asian/Pacific | 31 participants | 10 participants | 21 participants |
| Race/Ethnicity, Customized Hispanic | 53 participants | 32 participants | 21 participants |
| Race/Ethnicity, Customized Native American | 7 participants | 4 participants | 3 participants |
| Race/Ethnicity, Customized West Asian (Indian Subcontinent) | 79 participants | 45 participants | 34 participants |
| Region of Enrollment Australia | 64 participants | 28 participants | 36 participants |
| Region of Enrollment Belgium | 139 participants | 70 participants | 69 participants |
| Region of Enrollment Brazil | 36 participants | 18 participants | 18 participants |
| Region of Enrollment Canada | 79 participants | 43 participants | 36 participants |
| Region of Enrollment Czech Republic | 54 participants | 24 participants | 30 participants |
| Region of Enrollment Finland | 87 participants | 42 participants | 45 participants |
| Region of Enrollment France | 464 participants | 229 participants | 235 participants |
| Region of Enrollment Germany | 45 participants | 23 participants | 22 participants |
| Region of Enrollment India | 81 participants | 41 participants | 40 participants |
| Region of Enrollment Italy | 107 participants | 53 participants | 54 participants |
| Region of Enrollment Mexico | 14 participants | 7 participants | 7 participants |
| Region of Enrollment Netherlands | 30 participants | 15 participants | 15 participants |
| Region of Enrollment New Zealand | 46 participants | 22 participants | 24 participants |
| Region of Enrollment Portugal | 8 participants | 5 participants | 3 participants |
| Region of Enrollment Spain | 171 participants | 84 participants | 87 participants |
| Region of Enrollment Switzerland | 18 participants | 10 participants | 8 participants |
| Region of Enrollment United Kingdom | 93 participants | 49 participants | 44 participants |
| Region of Enrollment United States | 160 participants | 82 participants | 78 participants |
| Renal Sequential Organ Failure Assessment (SOFA) Score | 1.63 units on a scale STANDARD_DEVIATION 1.33 | 1.60 units on a scale STANDARD_DEVIATION 1.34 | 1.67 units on a scale STANDARD_DEVIATION 1.33 |
| Respiratory Sequential Organ Failure Assessment (SOFA) Score | 2.76 units on a scale STANDARD_DEVIATION 1.08 | 2.74 units on a scale STANDARD_DEVIATION 1.08 | 2.78 units on a scale STANDARD_DEVIATION 1.07 |
| Sex: Female, Male Female | 739 Participants | 379 Participants | 360 Participants |
| Sex: Female, Male Male | 957 Participants | 466 Participants | 491 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 151 / 833 | 119 / 833 |
| serious Total, serious adverse events | 119 / 833 | 96 / 833 |
Outcome results
Primary
28-Day All-Cause Mortality
Expressed as percentage of participants who died from any cause at Day 28 endpoint.
Time frame: Day 28
Population: All randomized participants with known mortality status at Day 28.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Drotrecogin Alfa (Activated) | 28-Day All-Cause Mortality | 26.4 percentage of participants |
| Placebo | 28-Day All-Cause Mortality | 24.2 percentage of participants |
Comparison: 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.p-value: 0.31395% CI: [0.923, 1.283]Chi-squared
Secondary
180-Day Mortality
Expressed as percentage of participants who died from any cause at Day 180 endpoint.
Time frame: Day 180
Population: All randomized participants with known mortality status at Day 180.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Drotrecogin Alfa (Activated) | 180-Day Mortality | 36.6 percentage of participants |
| Placebo | 180-Day Mortality | 35.9 percentage of participants |
p-value: 0.75895% CI: [0.898, 1.16]Chi-squared
Secondary
28-Day All-Cause Mortality in Participants With Severe Protein C Deficiency
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
Population: All randomized participants with severe protein C deficiency at Baseline with known mortality status at Day 28.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Drotrecogin Alfa (Activated) | 28-Day All-Cause Mortality in Participants With Severe Protein C Deficiency | 28.7 percentage of participants |
| Placebo | 28-Day All-Cause Mortality in Participants With Severe Protein C Deficiency | 30.8 percentage of participants |
p-value: 0.5495% CI: [0.737, 1.173]Chi-squared
Secondary
90-Day Mortality
Expressed as percentage of participants who died from any cause at Day 90 endpoint.
Time frame: Day 90
Population: All randomized participants with known mortality status at Day 90.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Drotrecogin Alfa (Activated) | 90-Day Mortality | 34.1 percentage of participants |
| Placebo | 90-Day Mortality | 32.7 percentage of participants |
p-value: 0.55695% CI: [0.909, 1.193]Chi-squared
Secondary
Average Cardiovascular Sequential Organ Failure Assessment (SOFA) Score 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.
Time frame: Day 1 through Day 28
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drotrecogin Alfa (Activated) | Average Cardiovascular Sequential Organ Failure Assessment (SOFA) Score Day 1 Through Day 28 | 1.92 units on a scale | Standard Deviation 1.31 |
| Placebo | Average Cardiovascular Sequential Organ Failure Assessment (SOFA) Score Day 1 Through Day 28 | 1.84 units on a scale | Standard Deviation 1.31 |
p-value: 0.181ANOVA
Secondary
Average Renal Sequential Organ Failure Assessment (SOFA) Score 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.
Time frame: Day 1 through Day 28
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drotrecogin Alfa (Activated) | Average Renal Sequential Organ Failure Assessment (SOFA) Score Day 1 Through Day 28 | 1.38 units on a scale | Standard Deviation 1.42 |
| Placebo | Average Renal Sequential Organ Failure Assessment (SOFA) Score Day 1 Through Day 28 | 1.28 units on a scale | Standard Deviation 1.4 |
p-value: 0.122ANOVA
Secondary
Average Respiratory Sequential Organ Failure Assessment (SOFA) Score 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.
Time frame: Day 1 through Day 28
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drotrecogin Alfa (Activated) | Average Respiratory Sequential Organ Failure Assessment (SOFA) Score Day 1 Through Day 28 | 2.31 units on a scale | Standard Deviation 1.05 |
| Placebo | Average Respiratory Sequential Organ Failure Assessment (SOFA) Score Day 1 Through Day 28 | 2.29 units on a scale | Standard Deviation 1.05 |
p-value: 0.733ANOVA
Secondary
EuroQoL Questionnaire-5 Dimensions (EQ-5D) Total Scores at Baseline, Days 28, 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).
Time frame: Baseline and Days 28 and 90 and 180
Population: All randomized participants with EQ-5D total score data at the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Drotrecogin Alfa (Activated) | EuroQoL Questionnaire-5 Dimensions (EQ-5D) Total Scores at Baseline, Days 28, 90 and 180 | Baseline (n=702, 705) | 0.60 units on a scale | Standard Deviation 0.35 |
| Drotrecogin Alfa (Activated) | EuroQoL Questionnaire-5 Dimensions (EQ-5D) Total Scores at Baseline, Days 28, 90 and 180 | Day 90 (n=480, 473) | 0.71 units on a scale | Standard Deviation 0.27 |
| Drotrecogin Alfa (Activated) | EuroQoL Questionnaire-5 Dimensions (EQ-5D) Total Scores at Baseline, Days 28, 90 and 180 | Day 180 (n=458, 448) | 0.77 units on a scale | Standard Deviation 0.23 |
| Drotrecogin Alfa (Activated) | EuroQoL Questionnaire-5 Dimensions (EQ-5D) Total Scores at Baseline, Days 28, 90 and 180 | Day 28 (n=509, 486) | 0.51 units on a scale | Standard Deviation 0.33 |
| Placebo | EuroQoL Questionnaire-5 Dimensions (EQ-5D) Total Scores at Baseline, Days 28, 90 and 180 | Day 90 (n=480, 473) | 0.71 units on a scale | Standard Deviation 0.28 |
| Placebo | EuroQoL Questionnaire-5 Dimensions (EQ-5D) Total Scores at Baseline, Days 28, 90 and 180 | Baseline (n=702, 705) | 0.60 units on a scale | Standard Deviation 0.35 |
| Placebo | EuroQoL Questionnaire-5 Dimensions (EQ-5D) Total Scores at Baseline, Days 28, 90 and 180 | Day 28 (n=509, 486) | 0.53 units on a scale | Standard Deviation 0.33 |
| Placebo | EuroQoL Questionnaire-5 Dimensions (EQ-5D) Total Scores at Baseline, Days 28, 90 and 180 | Day 180 (n=458, 448) | 0.76 units on a scale | Standard Deviation 0.25 |
p-value: 0.697ANOVA
p-value: 0.306ANOVA
p-value: 0.645ANOVA
p-value: 0.69ANOVA
Secondary
EuroQoL Questionnaire-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Scores at Baseline, Days 28, 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.
Time frame: Baseline and Days 28 and 90 and 180
Population: All randomized participants with EQ-5D VAS data at the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Drotrecogin Alfa (Activated) | EuroQoL Questionnaire-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Scores at Baseline, Days 28, 90 and 180 | Baseline (n=685, 679) | 54.21 units on a scale | Standard Deviation 26.99 |
| Drotrecogin Alfa (Activated) | EuroQoL Questionnaire-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Scores at Baseline, Days 28, 90 and 180 | Day 28 (n=500, 476) | 54.78 units on a scale | Standard Deviation 23.46 |
| Drotrecogin Alfa (Activated) | EuroQoL Questionnaire-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Scores at Baseline, Days 28, 90 and 180 | Day 90 (n=474, 469) | 64.41 units on a scale | Standard Deviation 21 |
| Drotrecogin Alfa (Activated) | EuroQoL Questionnaire-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Scores at Baseline, Days 28, 90 and 180 | Day 180 (n=456, 443) | 68.94 units on a scale | Standard Deviation 20.19 |
| Placebo | EuroQoL Questionnaire-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Scores at Baseline, Days 28, 90 and 180 | Day 180 (n=456, 443) | 69.08 units on a scale | Standard Deviation 20.5 |
| Placebo | EuroQoL Questionnaire-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Scores at Baseline, Days 28, 90 and 180 | Baseline (n=685, 679) | 54.37 units on a scale | Standard Deviation 27.95 |
| Placebo | EuroQoL Questionnaire-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Scores at Baseline, Days 28, 90 and 180 | Day 90 (n=474, 469) | 65.18 units on a scale | Standard Deviation 20.15 |
| Placebo | EuroQoL Questionnaire-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Scores at Baseline, Days 28, 90 and 180 | Day 28 (n=500, 476) | 55.24 units on a scale | Standard Deviation 22.89 |
p-value: 0.788ANOVA
p-value: 0.73ANOVA
p-value: 0.662ANOVA
p-value: 0.846ANOVA
Secondary
Median Survival Time
Time frame: Day 180
Population: All randomized participants excluding those with unknown mortality status at Day 180.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Drotrecogin Alfa (Activated) | Median Survival Time | NA days |
| Placebo | Median Survival Time | NA days |
Secondary
Percentage of Participants Discontinued Due to Adverse Events Any Time From Baseline Through Day 28 Endpoint
Time frame: Baseline through Day 28
Population: Participants who received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Drotrecogin Alfa (Activated) | Percentage of Participants Discontinued Due to Adverse Events Any Time From Baseline Through Day 28 Endpoint | 4.4 percentage of participants |
| Placebo | Percentage of Participants Discontinued Due to Adverse Events Any Time From Baseline Through Day 28 Endpoint | 3.0 percentage of participants |
p-value: 0.154Fisher Exact
Secondary
Quality of Life Short Form-12 (SF-12) Scores at Baseline, Days 28, 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.
Time frame: Baseline and Days 28 and 90 and 180
Population: All randomized participants with SF-12 score data at the specified time points.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Drotrecogin Alfa (Activated) | Quality of Life Short Form-12 (SF-12) Scores at Baseline, Days 28, 90 and 180 | Mental Component at Day 28 (n=484, 465) | 40.57 units on a scale | Standard Deviation 13.12 |
| Drotrecogin Alfa (Activated) | Quality of Life Short Form-12 (SF-12) Scores at Baseline, Days 28, 90 and 180 | Physical Component at Day 28 (n=484, 465) | 31.14 units on a scale | Standard Deviation 10.29 |
| Drotrecogin Alfa (Activated) | Quality of Life Short Form-12 (SF-12) Scores at Baseline, Days 28, 90 and 180 | Mental Component at Day 180 (n=450, 444) | 50.42 units on a scale | Standard Deviation 11.5 |
| Drotrecogin Alfa (Activated) | Quality of Life Short Form-12 (SF-12) Scores at Baseline, Days 28, 90 and 180 | Physical Component at Day 90 (n=474, 459) | 38.09 units on a scale | Standard Deviation 11.17 |
| Drotrecogin Alfa (Activated) | Quality of Life Short Form-12 (SF-12) Scores at Baseline, Days 28, 90 and 180 | Mental Component at Day 90 (n=474, 459) | 47.53 units on a scale | Standard Deviation 12.08 |
| Drotrecogin Alfa (Activated) | Quality of Life Short Form-12 (SF-12) Scores at Baseline, Days 28, 90 and 180 | Physical Component at Day 180 (n=450, 444) | 42.26 units on a scale | Standard Deviation 10.8 |
| Drotrecogin Alfa (Activated) | Quality of Life Short Form-12 (SF-12) Scores at Baseline, Days 28, 90 and 180 | Physical Component at Baseline (n=683, 696) | 39.14 units on a scale | Standard Deviation 12.04 |
| Drotrecogin Alfa (Activated) | Quality of Life Short Form-12 (SF-12) Scores at Baseline, Days 28, 90 and 180 | Mental Component at Baseline (n=683, 696) | 45.44 units on a scale | Standard Deviation 13.07 |
| Placebo | Quality of Life Short Form-12 (SF-12) Scores at Baseline, Days 28, 90 and 180 | Physical Component at Baseline (n=683, 696) | 39.22 units on a scale | Standard Deviation 12.1 |
| Placebo | Quality of Life Short Form-12 (SF-12) Scores at Baseline, Days 28, 90 and 180 | Mental Component at Day 28 (n=484, 465) | 41.45 units on a scale | Standard Deviation 12.59 |
| Placebo | Quality of Life Short Form-12 (SF-12) Scores at Baseline, Days 28, 90 and 180 | Mental Component at Day 90 (n=474, 459) | 48.52 units on a scale | Standard Deviation 12.36 |
| Placebo | Quality of Life Short Form-12 (SF-12) Scores at Baseline, Days 28, 90 and 180 | Mental Component at Day 180 (n=450, 444) | 50.55 units on a scale | Standard Deviation 11.7 |
| Placebo | Quality of Life Short Form-12 (SF-12) Scores at Baseline, Days 28, 90 and 180 | Mental Component at Baseline (n=683, 696) | 46.03 units on a scale | Standard Deviation 12.88 |
| Placebo | Quality of Life Short Form-12 (SF-12) Scores at Baseline, Days 28, 90 and 180 | Physical Component at Day 28 (n=484, 465) | 31.13 units on a scale | Standard Deviation 9.84 |
| Placebo | Quality of Life Short Form-12 (SF-12) Scores at Baseline, Days 28, 90 and 180 | Physical Component at Day 90 (n=474, 459) | 40.03 units on a scale | Standard Deviation 11.23 |
| Placebo | Quality of Life Short Form-12 (SF-12) Scores at Baseline, Days 28, 90 and 180 | Physical Component at Day 180 (n=450, 444) | 41.59 units on a scale | Standard Deviation 11.28 |
Comparison: Analysis on ranked data.p-value: 0.482ANOVA
Comparison: Analysis on ranked data.p-value: 0.584ANOVA
Comparison: Analysis on ranked data.p-value: 0.164ANOVA
Comparison: Analysis on ranked data.p-value: 0.666ANOVA
Comparison: Analysis on ranked data.p-value: 0.786ANOVA
Comparison: Analysis on ranked data.p-value: 0.16ANOVA
Comparison: Analysis on ranked data.p-value: 0.696ANOVA
Comparison: Analysis on ranked data.p-value: 0.966ANOVA
Other Pre-specified
Percentage of Participants With Serious Bleeding Events Within System Organ Class Any Time From 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.
Time frame: Baseline through Day 28
Population: Participants who received study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Drotrecogin Alfa (Activated) | Percentage of Participants With Serious Bleeding Events Within System Organ Class Any Time From Baseline Through Day 28 | with ≥1 event | 2.4 percentage of participants |
| Drotrecogin Alfa (Activated) | Percentage of Participants With Serious Bleeding Events Within System Organ Class Any Time From Baseline Through Day 28 | Gastrointestinal Disorders | 1.1 percentage of participants |
| Drotrecogin Alfa (Activated) | Percentage of Participants With Serious Bleeding Events Within System Organ Class Any Time From Baseline Through Day 28 | Injury, Poisoning And Procedural Complications | 0 percentage of participants |
| Drotrecogin Alfa (Activated) | Percentage of Participants With Serious Bleeding Events Within System Organ Class Any Time From Baseline Through Day 28 | Nervous System Disorders | 0.4 percentage of participants |
| Drotrecogin Alfa (Activated) | Percentage of Participants With Serious Bleeding Events Within System Organ Class Any Time From Baseline Through Day 28 | Renal And Urinary Disorders | 0.1 percentage of participants |
| Drotrecogin Alfa (Activated) | Percentage of Participants With Serious Bleeding Events Within System Organ Class Any Time From Baseline Through Day 28 | Respiratory, Thoracic And Mediastinal Disorders | 0.4 percentage of participants |
| Drotrecogin Alfa (Activated) | Percentage of Participants With Serious Bleeding Events Within System Organ Class Any Time From Baseline Through Day 28 | Vascular Disorders | 0.5 percentage of participants |
| Placebo | Percentage of Participants With Serious Bleeding Events Within System Organ Class Any Time From Baseline Through Day 28 | Injury, Poisoning And Procedural Complications | 0.6 percentage of participants |
| Placebo | Percentage of Participants With Serious Bleeding Events Within System Organ Class Any Time From Baseline Through Day 28 | with ≥1 event | 2.8 percentage of participants |
| Placebo | Percentage of Participants With Serious Bleeding Events Within System Organ Class Any Time From Baseline Through Day 28 | Renal And Urinary Disorders | 0 percentage of participants |
| Placebo | Percentage of Participants With Serious Bleeding Events Within System Organ Class Any Time From Baseline Through Day 28 | Gastrointestinal Disorders | 0.7 percentage of participants |
| Placebo | Percentage of Participants With Serious Bleeding Events Within System Organ Class Any Time From Baseline Through Day 28 | Vascular Disorders | 1.0 percentage of participants |
| Placebo | Percentage of Participants With Serious Bleeding Events Within System Organ Class Any Time From Baseline Through Day 28 | Respiratory, Thoracic And Mediastinal Disorders | 0.4 percentage of participants |
| Placebo | Percentage of Participants With Serious Bleeding Events Within System Organ Class Any Time From Baseline Through Day 28 | Nervous System Disorders | 0.4 percentage of participants |
p-value: 0.758Fisher Exact