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| ID | Type | Description | Link |
|---|---|---|---|
| F1K-US-EVDA |
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The study will evaluate the vasopressor requirement, hemodynamic response and measures of tissue perfusion in patients with septic shock receiving an infusion of drotrecogin alfa (activated) compared to patients not receiving drotrecogin alfa (activated).
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| drotrecogin alfa (activated) | Drug |
| Measure | Description | Time Frame |
|---|---|---|
| Cumulative Vasopressor Index (CVI) | CVI is sum of rankings for all vasopressors being used by patient at given time. Based on relative potency and dosing range for each vasopressor, each vasopressor was assigned ranking of 1 (low dosage) to 4 (high dosage). Range of CVI is between 1 and 20. | baseline to 24 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to 96 Hour Endpoint in Cumulative Vasopressor Index (CVI) | CVI is sum of rankings for all vasopressors being used by patient at given time. Based on relative potency and dosing range for each vasopressor, each vasopressor was assigned ranking of 1 (low dosage) to 4 (high dosage). Range of CVI is between 1 and 20. | Baseline, 96 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Bleeding Events | Serious bleeding event resulted in one of following outcomes, or was significant for any reason: initial/ prolonged inpatient hospitalization; life-threatening experience; persistent or significant disability/incapacity; congenital anomaly/birth defect. Intracranial hemorrhage was also considered serious bleeding event. | baseline to 7 days |
Inclusion:
Exclusion:
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| Name | Affiliation | Role |
|---|---|---|
| Call 1-877-CTLILLY (1-877-285-4559) or 1-317-651-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) | Eli Lilly and Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 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. | Camden | New Jersey | 08103 |
Although 22 and 21 patients were randomized to drotrecogin alfa (activated) [DrotA(a)] and control, respectively, 3 patients in DrotA(a) and 2 patients in control did not receive the per-protocol treatment, and as such, they have been excluded from the baseline demographics and the per-protocol efficacy analyses.
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| ID | Title | Description |
|---|---|---|
| FG000 | Drotrecogin Cohort | Group received drotrecogin alfa (activated) per physician-directed therapy |
| FG001 | Control Cohort | Group did not receive drotrecogin alfa (activated) per physician-directed therapy |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Drotrecogin Cohort | Group received drotrecogin alfa (activated) per physician-directed therapy |
| BG001 | Control Cohort | Group did not receive drotrecogin alfa (activated) per physician-directed therapy |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Cumulative Vasopressor Index (CVI) | CVI is sum of rankings for all vasopressors being used by patient at given time. Based on relative potency and dosing range for each vasopressor, each vasopressor was assigned ranking of 1 (low dosage) to 4 (high dosage). Range of CVI is between 1 and 20. | Number of per-protocol participants with values at baseline and 24 hours. | Posted | Mean | Standard Deviation | units on a scale | baseline to 24 hours |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Drotrecogin Cohort | Group received drotrecogin alfa (activated) per physician-directed therapy |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bradycardia | Cardiac disorders | MedDRA (10.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrilation | Cardiac disorders | MedDRA (9.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 1-800-545-5979 |
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| ID | Term |
|---|---|
| D018805 | Sepsis |
| D012772 | Shock, Septic |
| ID | Term |
|---|---|
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| C421124 | drotrecogin alfa activated |
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| Mean Arterial Pressure | baseline to 24 hours |
| Cardiovascular Performance Measures Obtained With a Pulmonary Artery Catheter - Cardiac Index | Cardiac Index = cardiac output divided by body surface area. | Baseline to 24 Hours |
| Lactate Level | Measures of global tissue perfusion and oxygenation were assessed via lactate levels. | Baseline to 6 Hours |
| Microcirculatory Measures From Sidestream Darkfield (SDF) Microscopy - Small Vessel Microvascular Flow Index (MFI) | Per vessel category (and per quadrant), scored flow as follows: no flow=0, intermediate flow=1, sluggish flow=2, continuous flow=3. The MFI per vessel category calculated with formula (Q1+Q2+Q3+Q4)/4. Scores could range from 0 (sluggish flow) to 3 (continuous flow). | Baseline to 24 Hours |
| Sequential Organ Failure Assessment (SOFA) Score at Baseline and 24 Hours | The presence of 5 organ dysfunctions (cardiovascular, respiratory, renal, hepatic, coagulation) was assessed using a Sequential Organ Failure Assessment (SOFA) score. Each organ has a possible dysfunction score of 0 to 4, for a total SOFA score range of 0 (no organ dysfunction) to 20 (all organs with dysfunction). | Baseline and 24 Hours |
| Change From Baseline in Creatinine Clearance (CrCl) at 24 Hours | CrCl = (urine creatinine*urine volume)/(plasma creatinine*time period of urine collection). Corrected CrCl = CrCl*1.73/body surface area. Change in CrCl = Endpoint minus baseline. | Baseline and 24 hours |
| 7 Day All-cause In-hospital Mortality | baseline to 7 days |
| Endogenous Protein C Level | Baseline to 24 Hours |
| Mixed Venous Oxygen Saturation | Cardiovascular performance measures obtained with a pulmonary catheter as assessed by mixed venous oxygen saturation. | Baseline to 24 Hours |
| United States |
| 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. | Akron | Ohio | 44307 | United States |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Race/Ethnicity | Number | participants |
|
| Cardiac Index | Cardiac Index = cardiac output divided by body surface area. | Mean | Standard Deviation | liters/minute/meters squared |
|
| Creatinine Clearance | CrCl = (urine creatinine*urine volume)/(plasma creatinine*time period of urine collection). Corrected CrCl = CrCl*1.73/body surface area. Change in CrCl = Endpoint minus baseline. | Mean | Standard Deviation | milliliter per minute |
|
| Cumulative Vasopressor Index (CVI) | CVI is sum of rankings for all vasopressors being used by patient at given time. Based on relative potency and dosing range for each vasopressor, each vasopressor was assigned ranking of 1 (low dosage) to 4 (high dosage). Range of CVI is between 1 and 20. | Mean | Standard Deviation | units on a scale |
|
| Lactate Levels | Measures of global tissue perfusion and oxygenation were assessed via lactate levels. | Mean | Standard Deviation | millimoles per Liter |
|
| Mean Arterial Pressure (MAP) | Mean | Standard Deviation | mm Hg |
|
| Mixed Venous Oxygen Saturation | Cardiovascular performance measures obtained with a pulmonary catheter as assessed by mixed venous oxygen saturation. | Mean | Standard Deviation | percent saturation mixed venous oxygen |
|
| Number of Organ Dysfunctions | Mean | Standard Deviation | number of organ dysfunctions |
|
| Ratio of Arterial Partial Pressure of Oxygen to Fraction of Inspired Oxygen (PaO2/FiO2) | Mean | Inter-Quartile Range | mm Hg / percent inspired oxygen |
|
| Total Sequential Organ Failure Assessment Score | The presence of 5 organ dysfunctions (cardiovascular, respiratory, renal, hepatic, coagulation) was assessed using a Sequential Organ Failure Assessment (SOFA) score. Each organ has a possible dysfunction score of 0 to 4, for a total SOFA score range of 0 (no organ dysfunction) to 20 (all organs with dysfunction). | Mean | Standard Deviation | units on a scale |
|
|
|
|
| Secondary | Change From Baseline to 96 Hour Endpoint in Cumulative Vasopressor Index (CVI) | CVI is sum of rankings for all vasopressors being used by patient at given time. Based on relative potency and dosing range for each vasopressor, each vasopressor was assigned ranking of 1 (low dosage) to 4 (high dosage). Range of CVI is between 1 and 20. | Number of per-protocol participants with values at baseline and 96 hours. | Posted | Mean | Standard Deviation | units on a scale | Baseline, 96 hours |
|
|
|
|
| Secondary | Mean Arterial Pressure | Number of per-protocol participants with values at baseline and 24 hours. | Posted | Mean | Standard Deviation | mm Hg | baseline to 24 hours |
|
|
|
|
| Secondary | Cardiovascular Performance Measures Obtained With a Pulmonary Artery Catheter - Cardiac Index | Cardiac Index = cardiac output divided by body surface area. | Number of per-protocol participants with values at baseline and 24 hours. | Posted | Mean | Standard Deviation | liters/minute/meters squared | Baseline to 24 Hours |
|
|
|
|
| Secondary | Lactate Level | Measures of global tissue perfusion and oxygenation were assessed via lactate levels. | Number of per-protocol participants with values at baseline and 6 hours. | Posted | Mean | Standard Deviation | millimoles per Liter | Baseline to 6 Hours |
|
|
|
|
| Secondary | Microcirculatory Measures From Sidestream Darkfield (SDF) Microscopy - Small Vessel Microvascular Flow Index (MFI) | Per vessel category (and per quadrant), scored flow as follows: no flow=0, intermediate flow=1, sluggish flow=2, continuous flow=3. The MFI per vessel category calculated with formula (Q1+Q2+Q3+Q4)/4. Scores could range from 0 (sluggish flow) to 3 (continuous flow). | Number of per-protocol participants with values at baseline, 12, and 24 hours. | Posted | Mean | Standard Deviation | units on a scale | Baseline to 24 Hours |
|
|
|
|
| Secondary | Sequential Organ Failure Assessment (SOFA) Score at Baseline and 24 Hours | The presence of 5 organ dysfunctions (cardiovascular, respiratory, renal, hepatic, coagulation) was assessed using a Sequential Organ Failure Assessment (SOFA) score. Each organ has a possible dysfunction score of 0 to 4, for a total SOFA score range of 0 (no organ dysfunction) to 20 (all organs with dysfunction). | Number of per-protocol participants with values at baseline and 24 hours. | Posted | Mean | Standard Deviation | units on a scale | Baseline and 24 Hours |
|
|
|
|
| Secondary | Change From Baseline in Creatinine Clearance (CrCl) at 24 Hours | CrCl = (urine creatinine*urine volume)/(plasma creatinine*time period of urine collection). Corrected CrCl = CrCl*1.73/body surface area. Change in CrCl = Endpoint minus baseline. | Number of per-protocol participants with values at baseline and 24 hours. | Posted | Mean | Standard Deviation | milliliter per minute | Baseline and 24 hours |
|
|
|
|
| Secondary | 7 Day All-cause In-hospital Mortality | All enrolled patients | Posted | Number | partipants | baseline to 7 days |
|
|
|
| Secondary | Endogenous Protein C Level | Number of per-protocol participants with values at baseline, 12, and 24 hours. | Posted | Mean | Standard Deviation | percentage of Protein C activity | Baseline to 24 Hours |
|
|
|
|
| Other Pre-specified | Number of Participants With Bleeding Events | Serious bleeding event resulted in one of following outcomes, or was significant for any reason: initial/ prolonged inpatient hospitalization; life-threatening experience; persistent or significant disability/incapacity; congenital anomaly/birth defect. Intracranial hemorrhage was also considered serious bleeding event. | All enrolled patients | Posted | Number | participants | baseline to 7 days |
|
|
|
| Secondary | Mixed Venous Oxygen Saturation | Cardiovascular performance measures obtained with a pulmonary catheter as assessed by mixed venous oxygen saturation. | Number of per-protocol participants with values at baseline and 24 hours. | Posted | Mean | Standard Deviation | percent saturation mixed venous oxygen | Baseline to 24 Hours |
|
|
|
|
| 4 |
| 4 |
| EG001 | Control Cohort | Group did not receive drotrecogin alfa (activated) per physician-directed therapy | 3 | 0 |
| Cardiac arrest | Cardiac disorders | MedDRA (9.0) | Systematic Assessment |
|
| Ventricular tachycardia | Cardiac disorders | MedDRA (9.0) | Systematic Assessment |
|
| Right sided hemothorax | Injury, poisoning and procedural complications | MedDRA (9.0) | Systematic Assessment |
|
| Hemorrage intraperitoneal | Vascular disorders | MedDRA (10.0) | Systematic Assessment |
|
| Gastrointestinal bleeding | Gastrointestinal disorders | MedDRA (9.0) | Systematic Assessment |
|
| Gross hematuria | Renal and urinary disorders | MedDRA (9.1) | Systematic Assessment |
|
| Oropharynx blood and ecchymoses | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
|
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| D013568 |
| Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |
| 0.871 |
24-Hour Change from Baseline p-value |
| 95 |
| No |
| Superiority or Other |
| 0.702 |
24-Hour Change from Baseline p-value |
| 95 |
| No |
| Superiority or Other |
| 0.027 |
6-Hour Change from Baseline p-value |
| 95 |
| No |
| Superiority or Other |
| 24 Hour |
|
| 24 Hour Change from Baseline |
|
| 0.083 |
12-Hour p-value |
| 95 |
| No |
| Superiority or Other |
| Repeated Measures - propensity adjusted | 0.810 | 24-Hour p-value | 95 | No | Superiority or Other |
| Repeated Measures - propensity adjusted | 0.623 | 24-Hour Change from Baseline p-value | 95 | No | Superiority or Other |
| 0.575 |
24-Hour p-value |
| 95 |
| No |
| Superiority or Other |
| 24 Hours |
|
| 24 Hour Change from Baseline |
|
| 0.129 |
12-Hour p-value |
| 95 |
| No |
| Superiority or Other |
| Repeated Measures - propensity adjusted | 0.030 | 24-Hour p-value | 95 | No | Superiority or Other |
| Repeated Measures - propensity adjusted | 0.002 | 24-Hour Change from Baseline p-value | 95 | No | Superiority or Other |
| 0.234 |
24-Hour Change from Baseline p-value |
| 95 |
| No |
| Superiority or Other |