Severe Sepsis
Conditions
Brief summary
In this trial, patients with severe sepsis and low protein C levels will receive drotrecogin alfa (activated) at the normal, approved dose and time of administration \[24 microgram/kilogram/hour (mcg/kg/hour) for 96 hours\] or will receive the normal, approved dose or higher doses than the approved dose for a longer administration time. After the drug administration is complete, the protein C levels from the patients receiving the normal, approved dose will be compared to protein C levels from patients receiving the normal, approved dose or higher dose for a longer duration to determine if the protein C levels improve faster if given higher dose and/or longer administration time. Note: The protocol was amended to remove the option of shorter infusion durations.
Interventions
intravenous
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 a suspected or proven infection * Must have two or more sepsis-associated organ dysfunctions
Exclusion criteria
* Documented multiple organ dysfunction greater than 24 hours prior to start of study drug * Actual body weight less than 30 kg or more than 135 kg * Platelet count less than 30,000/mm\^3 * Active internal bleeding or at increased risk of bleeding * Not expected to survive 28 days given the patient's pre-existing uncorrectable medical condition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Protein C Levels From Day 1 to Day 7 | Day 1, Day 7 | Mean change in protein C from Study Day 1 to Study Day 7 was tested using an unadjusted two-sample t-test with a two-sided alpha of 0.05. To be included in the primary analysis, Intention-to-Treat (ITT) patients must have at least 1 protein C value available at 24 hours or earlier and at least 1 protein C value at a post-24-hour timepoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Protein C Level From Study Day 1 to Study Day 7 in Patients With Moderate and Severe Protein C Deficiency | Day 1, Day 7 | Moderate Protein C Deficiency: A protein C level greater than half the lower limit of normal. Severe Protein C Deficiency: A protein C level less than or equal to half the lower limit of normal. |
| Day 28 All-Cause Mortality | Day 0 through Day 28 | — |
| Hospital Mortality (up to Day 90) | Day 0 to hospital discharge or Day 90 | — |
| Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period | Day 0 through Day 28 | Serious bleeding events (SBE): intracranial hemorrhage, life-threatening or fatal bleed, or bleeding event assessed as an SAE. Patients may have multiple events with onset in different time periods. SAEs include SBEs. The 3 SBEs in Alternative-Moderate Deficiency arm (days 5-8) occurred after completion of study drug infusion. One event (pleural haemorrhage) occurred same day of completion of infusion and 2 events (cerebral haemorrhage, shock haemorrhagic) occurred day after completion. |
| Mortality by Protein C Normalized Versus Not-normalized | 28 days | Normalization was defined as having 2 consecutive protein C measurements above the lower limit of normal through Study Day 7. |
| 28-Day Time Averaged Sequential Organ Failure (SOFA) Score | Day 0, Day 28 | 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). SOFA scores were time-averaged. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mortality for Severe Protein C Deficiency | 28 Days, up to 90 days | Twenty-eight day mortality is the patient's mortality status at the predefined timepoint of 672 hours from the start of study drug infusion. Hospital mortality is the patient's survival status at the end of the hospital stay or study day 90 (if the patient remains in the hospital). |
Countries
Belgium, Canada, Finland, France, Germany, Puerto Rico, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
Efficacy results are only provided for the intent-to-treat (ITT) population (patients who actually received the randomized treatment after the 24 hour pretreatment period).
Participants by arm
| Arm | Count |
|---|---|
| Standard Therapy 24 mcg/kg/hr for 24 hours, followed by 24 mcg/kg/hr for an additional 72 hours | 227 |
| Alternative Therapy Moderate Protein C Deficiency: 24 mcg/kg/hr for 24 hours, followed by 24 mcg/kg/hr for an additional 72 to 144 hours Severe Protein C Deficiency: 24 mcg/kg/hr for 24 hours, followed by 30 or 36 mcg/kg/hr for an additional 72 to 144 hours | 206 |
| Randomized Non-ITT Population | 53 |
| Total | 486 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Physician Decision | 3 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Randomized Non-ITT Population | Standard Therapy | Total | Alternative Therapy |
|---|---|---|---|---|
| Acute Physiology And Chronic Health Evaluation (APACHE) II Score | 28.26 units on a scale STANDARD_DEVIATION 8.05 | 26.34 units on a scale STANDARD_DEVIATION 7.7 | 26.47 units on a scale STANDARD_DEVIATION 7.59 | 26.15 units on a scale STANDARD_DEVIATION 7.31 |
| Age Continuous | 66.63 years STANDARD_DEVIATION 12.82 | 62.31 years STANDARD_DEVIATION 16.11 | 62.61 years STANDARD_DEVIATION 15.12 | 61.91 years STANDARD_DEVIATION 14.44 |
| Central laboratory protein C class Moderate deficiency | 9 participants | 94 participants | 179 participants | 76 participants |
| Central laboratory protein C class Normal | 0 participants | 9 participants | 18 participants | 9 participants |
| Central laboratory protein C class Severe deficiency | 31 participants | 97 participants | 228 participants | 100 participants |
| Central laboratory protein C class Unknown | 13 participants | 27 participants | 61 participants | 21 participants |
| Mechanical ventilation No | 9 participants | 49 participants | 106 participants | 48 participants |
| Mechanical ventilation Yes | 44 participants | 178 participants | 380 participants | 158 participants |
| Number of organ dysfunctions | 3.28 organ dysfunctions STANDARD_DEVIATION 0.93 | 3.08 organ dysfunctions STANDARD_DEVIATION 0.86 | 3.10 organ dysfunctions STANDARD_DEVIATION 0.86 | 3.08 organ dysfunctions STANDARD_DEVIATION 0.84 |
| Protein C level | 30 Percent Protein C Activity STANDARD_DEVIATION 18 | 44 Percent Protein C Activity STANDARD_DEVIATION 19 | 42 Percent Protein C Activity STANDARD_DEVIATION 20 | 41 Percent Protein C Activity STANDARD_DEVIATION 20 |
| Race/Ethnicity, Customized African | 2 Participants | 13 Participants | 19 Participants | 4 Participants |
| Race/Ethnicity, Customized Caucasian | 51 Participants | 204 Participants | 444 Participants | 189 Participants |
| Race/Ethnicity, Customized East Asian | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Hispanic | 0 Participants | 9 Participants | 17 Participants | 8 Participants |
| Race/Ethnicity, Customized Native American | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized West Asian | 0 Participants | 1 Participants | 3 Participants | 2 Participants |
| Recent Surgery No | 28 participants | 159 participants | 331 participants | 144 participants |
| Recent Surgery Unknown | 0 participants | 0 participants | 1 participants | 1 participants |
| Recent Surgery Yes | 25 participants | 68 participants | 154 participants | 61 participants |
| Region of Enrollment Australia | 1 participants | 2 participants | 4 participants | 1 participants |
| Region of Enrollment Belgium | 6 participants | 27 participants | 56 participants | 23 participants |
| Region of Enrollment Canada | 4 participants | 22 participants | 47 participants | 21 participants |
| Region of Enrollment Finland | 2 participants | 29 participants | 61 participants | 30 participants |
| Region of Enrollment France | 9 participants | 37 participants | 79 participants | 33 participants |
| Region of Enrollment Germany | 1 participants | 14 participants | 27 participants | 12 participants |
| Region of Enrollment Italy | 0 participants | 1 participants | 2 participants | 1 participants |
| Region of Enrollment Puerto Rico | 0 participants | 2 participants | 6 participants | 4 participants |
| Region of Enrollment Spain | 12 participants | 19 participants | 47 participants | 16 participants |
| Region of Enrollment United Kingdom | 10 participants | 32 participants | 71 participants | 29 participants |
| Region of Enrollment United States | 8 participants | 42 participants | 86 participants | 36 participants |
| Sex: Female, Male Female | 20 Participants | 90 Participants | 186 Participants | 76 Participants |
| Sex: Female, Male Male | 33 Participants | 137 Participants | 300 Participants | 130 Participants |
| Time of onset of Second organ dysfunction to start of drug infusion | 15.8 hours STANDARD_DEVIATION 7.2 | 15.3 hours STANDARD_DEVIATION 7 | 15.3 hours STANDARD_DEVIATION 7 | 15.0 hours STANDARD_DEVIATION 7 |
| Total Sequential Organ Failure Assessment (SOFA) score | 9.09 units on a scale STANDARD_DEVIATION 2.25 | 8.38 units on a scale STANDARD_DEVIATION 2.83 | 8.57 units on a scale STANDARD_DEVIATION 2.72 | 8.65 units on a scale STANDARD_DEVIATION 2.7 |
| Use of vasopressor No | 2 participants | 37 participants | 62 participants | 23 participants |
| Use of vasopressor Yes | 51 participants | 190 participants | 424 participants | 183 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 51 / 250 | 46 / 236 |
| serious Total, serious adverse events | 33 / 250 | 48 / 236 |
Outcome results
Primary
Mean Change in Protein C Levels From Day 1 to Day 7
Mean change in protein C from Study Day 1 to Study Day 7 was tested using an unadjusted two-sample t-test with a two-sided alpha of 0.05. To be included in the primary analysis, Intention-to-Treat (ITT) patients must have at least 1 protein C value available at 24 hours or earlier and at least 1 protein C value at a post-24-hour timepoint.
Time frame: Day 1, Day 7
Population: Intent to Treat (ITT) Last Observation Carried Forward (LOCF) population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard Therapy | Mean Change in Protein C Levels From Day 1 to Day 7 | Protein C Day 1, n=226, n=205 | 55 Percent Protein C Activity | Standard Deviation 24 |
| Standard Therapy | Mean Change in Protein C Levels From Day 1 to Day 7 | Protein C Day 7, n=221, n=203 | 79 Percent Protein C Activity | Standard Deviation 33 |
| Standard Therapy | Mean Change in Protein C Levels From Day 1 to Day 7 | Change in Protein C, Day 1 to Day 7, n=221, n=202 | 24 Percent Protein C Activity | Standard Deviation 29 |
| Alternative Therapy | Mean Change in Protein C Levels From Day 1 to Day 7 | Protein C Day 1, n=226, n=205 | 52 Percent Protein C Activity | Standard Deviation 24 |
| Alternative Therapy | Mean Change in Protein C Levels From Day 1 to Day 7 | Protein C Day 7, n=221, n=203 | 83 Percent Protein C Activity | Standard Deviation 35 |
| Alternative Therapy | Mean Change in Protein C Levels From Day 1 to Day 7 | Change in Protein C, Day 1 to Day 7, n=221, n=202 | 31 Percent Protein C Activity | Standard Deviation 29 |
p-value: 0.011t-test, 2 sided
Secondary
28-Day Time Averaged Sequential Organ Failure (SOFA) 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). SOFA scores were time-averaged.
Time frame: Day 0, Day 28
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard Therapy | 28-Day Time Averaged Sequential Organ Failure (SOFA) Score | Total | 5.96 Units on a scale | Standard Deviation 5.21 |
| Standard Therapy | 28-Day Time Averaged Sequential Organ Failure (SOFA) Score | Cardiovascular | 1.28 Units on a scale | Standard Deviation 1.21 |
| Standard Therapy | 28-Day Time Averaged Sequential Organ Failure (SOFA) Score | Respiratory | 2.22 Units on a scale | Standard Deviation 0.99 |
| Standard Therapy | 28-Day Time Averaged Sequential Organ Failure (SOFA) Score | Renal | 0.92 Units on a scale | Standard Deviation 1.28 |
| Standard Therapy | 28-Day Time Averaged Sequential Organ Failure (SOFA) Score | Hematology | 0.80 Units on a scale | Standard Deviation 1.16 |
| Standard Therapy | 28-Day Time Averaged Sequential Organ Failure (SOFA) Score | Liver | 0.78 Units on a scale | Standard Deviation 1.22 |
| Alternative Therapy | 28-Day Time Averaged Sequential Organ Failure (SOFA) Score | Hematology | 0.93 Units on a scale | Standard Deviation 1.2 |
| Alternative Therapy | 28-Day Time Averaged Sequential Organ Failure (SOFA) Score | Total | 6.62 Units on a scale | Standard Deviation 5.23 |
| Alternative Therapy | 28-Day Time Averaged Sequential Organ Failure (SOFA) Score | Renal | 1.04 Units on a scale | Standard Deviation 1.31 |
| Alternative Therapy | 28-Day Time Averaged Sequential Organ Failure (SOFA) Score | Cardiovascular | 1.41 Units on a scale | Standard Deviation 1.26 |
| Alternative Therapy | 28-Day Time Averaged Sequential Organ Failure (SOFA) Score | Liver | 0.89 Units on a scale | Standard Deviation 1.21 |
| Alternative Therapy | 28-Day Time Averaged Sequential Organ Failure (SOFA) Score | Respiratory | 2.38 Units on a scale | Standard Deviation 0.88 |
p-value: 0.19t-test, 2 sided
p-value: 0.268t-test, 2 sided
p-value: 0.082t-test, 2 sided
p-value: 0.367t-test, 2 sided
p-value: 0.274t-test, 2 sided
p-value: 0.341t-test, 2 sided
Secondary
Day 28 All-Cause Mortality
Time frame: Day 0 through Day 28
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard Therapy | Day 28 All-Cause Mortality | Deceased at Day 28 | 16.1 percentage of participants |
| Standard Therapy | Day 28 All-Cause Mortality | Alive at Day 28 | 83.9 percentage of participants |
| Alternative Therapy | Day 28 All-Cause Mortality | Deceased at Day 28 | 24.9 percentage of participants |
| Alternative Therapy | Day 28 All-Cause Mortality | Alive at Day 28 | 75.1 percentage of participants |
p-value: 0.03Fisher Exact
Secondary
Hospital Mortality (up to Day 90)
Time frame: Day 0 to hospital discharge or Day 90
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard Therapy | Hospital Mortality (up to Day 90) | Discharged Alive | 79.5 Percentage of participants |
| Standard Therapy | Hospital Mortality (up to Day 90) | Deceased | 20.5 Percentage of participants |
| Alternative Therapy | Hospital Mortality (up to Day 90) | Discharged Alive | 72.2 Percentage of participants |
| Alternative Therapy | Hospital Mortality (up to Day 90) | Deceased | 27.8 Percentage of participants |
p-value: 0.09Fisher Exact
Secondary
Mean Change in Protein C Level From Study Day 1 to Study Day 7 in Patients With Moderate and Severe Protein C Deficiency
Moderate Protein C Deficiency: A protein C level greater than half the lower limit of normal. Severe Protein C Deficiency: A protein C level less than or equal to half the lower limit of normal.
Time frame: Day 1, Day 7
Population: ITT moderately deficient population, ITT severely deficient population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard Therapy | Mean Change in Protein C Level From Study Day 1 to Study Day 7 in Patients With Moderate and Severe Protein C Deficiency | Moderate n=175, n=171 | 24 Percent Protein C Activity | Standard Deviation 28 |
| Standard Therapy | Mean Change in Protein C Level From Study Day 1 to Study Day 7 in Patients With Moderate and Severe Protein C Deficiency | Severe n=46, n=31 | 25 Percent Protein C Activity | Standard Deviation 32 |
| Alternative Therapy | Mean Change in Protein C Level From Study Day 1 to Study Day 7 in Patients With Moderate and Severe Protein C Deficiency | Moderate n=175, n=171 | 30 Percent Protein C Activity | Standard Deviation 29 |
| Alternative Therapy | Mean Change in Protein C Level From Study Day 1 to Study Day 7 in Patients With Moderate and Severe Protein C Deficiency | Severe n=46, n=31 | 38 Percent Protein C Activity | Standard Deviation 27 |
p-value: 0.047t-test, 2 sided
p-value: 0.063t-test, 2 sided
Secondary
Mortality by Protein C Normalized Versus Not-normalized
Normalization was defined as having 2 consecutive protein C measurements above the lower limit of normal through Study Day 7.
Time frame: 28 days
Population: ITT Population - All patients who are randomly assigned to treatment and receive any amount of randomized therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Therapy | Mortality by Protein C Normalized Versus Not-normalized | 10.3 Percentage of participants |
| Alternative Therapy | Mortality by Protein C Normalized Versus Not-normalized | 32.0 Percentage of participants |
p-value: <0.0001Fisher Exact
Secondary
Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period
Serious bleeding events (SBE): intracranial hemorrhage, life-threatening or fatal bleed, or bleeding event assessed as an SAE. Patients may have multiple events with onset in different time periods. SAEs include SBEs. The 3 SBEs in Alternative-Moderate Deficiency arm (days 5-8) occurred after completion of study drug infusion. One event (pleural haemorrhage) occurred same day of completion of infusion and 2 events (cerebral haemorrhage, shock haemorrhagic) occurred day after completion.
Time frame: Day 0 through Day 28
Population: Randomized participants who received randomized therapy (intention to treat population).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard Therapy | Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period | Serious Bleeding Events: Study Days 0 through 4 | 0 number of patients with at least 1 event |
| Standard Therapy | Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period | Serious Bleeding Events: Study Days 5 through 8 | 1 number of patients with at least 1 event |
| Standard Therapy | Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period | Serious Bleeding Events: Study Days 9 through 28 | 0 number of patients with at least 1 event |
| Standard Therapy | Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period | Serious Adverse Events: Study Days 0 through 4 | 0 number of patients with at least 1 event |
| Standard Therapy | Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period | Serious Adverse Events: Study Days 5 through 8 | 2 number of patients with at least 1 event |
| Standard Therapy | Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period | Serious Adverse Events: Study Days 9 through 28 | 3 number of patients with at least 1 event |
| Alternative Therapy | Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period | Serious Adverse Events: Study Days 9 through 28 | 8 number of patients with at least 1 event |
| Alternative Therapy | Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period | Serious Adverse Events: Study Days 0 through 4 | 10 number of patients with at least 1 event |
| Alternative Therapy | Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period | Serious Bleeding Events: Study Days 0 through 4 | 2 number of patients with at least 1 event |
| Alternative Therapy | Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period | Serious Bleeding Events: Study Days 9 through 28 | 1 number of patients with at least 1 event |
| Alternative Therapy | Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period | Serious Bleeding Events: Study Days 5 through 8 | 0 number of patients with at least 1 event |
| Alternative Therapy | Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period | Serious Adverse Events: Study Days 5 through 8 | 4 number of patients with at least 1 event |
| Alternative Therapy - Severe Deficiency | Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period | Serious Bleeding Events: Study Days 5 through 8 | 0 number of patients with at least 1 event |
| Alternative Therapy - Severe Deficiency | Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period | Serious Bleeding Events: Study Days 9 through 28 | 0 number of patients with at least 1 event |
| Alternative Therapy - Severe Deficiency | Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period | Serious Adverse Events: Study Days 0 through 4 | 5 number of patients with at least 1 event |
| Alternative Therapy - Severe Deficiency | Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period | Serious Adverse Events: Study Days 9 through 28 | 4 number of patients with at least 1 event |
| Alternative Therapy - Severe Deficiency | Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period | Serious Adverse Events: Study Days 5 through 8 | 1 number of patients with at least 1 event |
| Alternative Therapy - Severe Deficiency | Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period | Serious Bleeding Events: Study Days 0 through 4 | 0 number of patients with at least 1 event |
| Alternative Therapy - Moderate Deficiency | Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period | Serious Adverse Events: Study Days 5 through 8 | 8 number of patients with at least 1 event |
| Alternative Therapy - Moderate Deficiency | Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period | Serious Adverse Events: Study Days 9 through 28 | 14 number of patients with at least 1 event |
| Alternative Therapy - Moderate Deficiency | Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period | Serious Bleeding Events: Study Days 5 through 8 | 3 number of patients with at least 1 event |
| Alternative Therapy - Moderate Deficiency | Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period | Serious Adverse Events: Study Days 0 through 4 | 17 number of patients with at least 1 event |
| Alternative Therapy - Moderate Deficiency | Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period | Serious Bleeding Events: Study Days 0 through 4 | 9 number of patients with at least 1 event |
| Alternative Therapy - Moderate Deficiency | Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period | Serious Bleeding Events: Study Days 9 through 28 | 1 number of patients with at least 1 event |
Post Hoc
Mortality for Moderate Protein C Deficiency by Infusion Duration
Time frame: 28 Days
Population: ITT Population - ITT Switch-No Population, ITT patients who did not answer yes to the switch question.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard Therapy | Mortality for Moderate Protein C Deficiency by Infusion Duration | <97 Hours n=65, n=71 | 13.8 percent participants deceased |
| Standard Therapy | Mortality for Moderate Protein C Deficiency by Infusion Duration | >=97 Hours n=70, n=71 | 11.4 percent participants deceased |
| Alternative Therapy | Mortality for Moderate Protein C Deficiency by Infusion Duration | <97 Hours n=65, n=71 | 28.2 percent participants deceased |
| Alternative Therapy | Mortality for Moderate Protein C Deficiency by Infusion Duration | >=97 Hours n=70, n=71 | 23.9 percent participants deceased |
Other Pre-specified
Mortality for Severe Protein C Deficiency
Twenty-eight day mortality is the patient's mortality status at the predefined timepoint of 672 hours from the start of study drug infusion. Hospital mortality is the patient's survival status at the end of the hospital stay or study day 90 (if the patient remains in the hospital).
Time frame: 28 Days, up to 90 days
Population: ITT Population - All patients who are randomly assigned to treatment and receive any amount of randomized therapy. ITT patients with severe protein C deficiency. Severe deficiency is defined by the 24-hour local laboratory protein C value reported to the Interactive voice response system (IVRS).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard Therapy | Mortality for Severe Protein C Deficiency | 28 Day Mortality - Alive at Day 28 | 68.6 Percentage of participants |
| Standard Therapy | Mortality for Severe Protein C Deficiency | 28 Day Mortality - Deceased at Day 28 | 31.4 Percentage of participants |
| Standard Therapy | Mortality for Severe Protein C Deficiency | Hospital Mortality - Deceased | 33.3 Percentage of participants |
| Standard Therapy | Mortality for Severe Protein C Deficiency | Hospital Mortality - Discharged Alive | 66.7 Percentage of participants |
| Alternative Therapy | Mortality for Severe Protein C Deficiency | Hospital Mortality - Discharged Alive | 69.7 Percentage of participants |
| Alternative Therapy | Mortality for Severe Protein C Deficiency | Hospital Mortality - Deceased | 30.3 Percentage of participants |
| Alternative Therapy | Mortality for Severe Protein C Deficiency | 28 Day Mortality - Deceased at Day 28 | 24.2 Percentage of participants |
| Alternative Therapy | Mortality for Severe Protein C Deficiency | 28 Day Mortality - Alive at Day 28 | 75.8 Percentage of participants |
p-value: 0.622Pearson's chi-square test
p-value: 0.815Fisher Exact