Septic Shock
Conditions
Brief summary
This is a double-blind, randomised, placebo-controlled, two-part adaptive clinical trial. The trial is designed to investigate the efficacy and safety of multiple dosing regimens of selepressin and to confirm the efficacy and safety of one dosing regimen in treatment of adult patients with septic shock requiring vasopressor.
Interventions
DRUGselepressin
DRUGplacebo
Sponsors
Ferring Pharmaceuticals
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
* 18 years of age or older * Proven or suspected infection * Septic shock defined as hypotension requiring vasopressor treatment despite adequate fluid resuscitation * Informed consent obtained in accordance with local regulations
Exclusion criteria
* Not possible to initiate trial drug treatment within 12 hours from onset of vasopressor treatment for septic shock * Primary cause of hypotension not due to sepsis * Previous severe sepsis with intensive care unit admission within this hospital stay * Known/suspected acute mesenteric ischaemia * Suspicion of concomitant acute coronary syndrome based on clinical symptoms and/or ECG during this episode of septic shock * Chronic mechanical ventilation for any reason OR severe chronic obstructive pulmonary disease (COPD) requiring either continuous daily oxygen use during the preceding 30 days or mechanical ventilation (for acute exacerbation of COPD) during the preceding 30 days * Received bone marrow transplant during the preceding 6 months or chemotherapy during the preceding 30 days for lymphoma or leukemia * Known to be pregnant * Decision to limit full care taken before obtaining informed consent * Use of vasopressin in the past 12 hours prior to start of trial drug treatment or use of terlipressin within 7 days prior to start of trial drug treatment * Prior enrolment in the trial * Prior use of an investigational medicinal product within the last month OR planned or concurrent participation in a clinical trial for any investigational drug or investigational device
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Vasopressor- and Mechanical Ventilator-free Days (PVFDs) | Up to Day 30 | Composite endpoint defined as number of days from start of treatment to 30 days thereafter during which subject is: 1. Alive. However, if patient dies within these 30-days then PVFDs will be zero even if there is a period during which subject is alive and free of both vasopressor treatment and mechanical ventilation; 2. Free of treatment with vasopressors: Less than 60 min during any contiguous 24-h period. If a patient requires vasopressors longer than 60 min in total during any 24-h period, the intervening intervals during which they are free of vasopressors will not be included in the determination of PVFDs; 3. Free of any mechanical ventilation: Less than 60 min during any contiguous 24-h period. If a patient requires mechanical ventilation longer than 60 min in total during any 24-h period, the intervening intervals during which they are not receiving mechanical ventilation will not be included in the period free of mechanical ventilation in the determination of PVFDs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Renal Replacement Therapy (RRT)-Free Days | Up to Day 30 | RRT-free days was defined as the number of days a subject is free of treatment with any form of RRT (continuous RRT, intermittent hemodialysis or peritoneal dialysis) and the intermittent periods were not included. RRT-free days was analyzed excluding subjects on RRT for chronic renal failure at time of randomization. |
| Intensive Care Unit (ICU)-Free Days | Up to Day 30 | The ICU free days, as for the PVFDs, reflect the time from last discharge of the ICU to Day 30 with an absolute penalty for mortality, i.e., any subject that died within this 30-day period was assigned zero value). |
| Vasopressor-free Days up to Day 30 | Up to Day 30 | Number of days from start of treatment to 30 days thereafter during which the subject is free of treatment with vasopressors, i.e. less than 60 min during any contiguous 24-h period. |
| Mechanical Ventilator-free Days up to Day 30 | Up to Day 30 | Number of days from start of treatment to 30 days thereafter during which the subject is free of any mechanical ventilation, i.e. less than 60 min during any contiguous 24-h period. |
| Duration of Septic Shock (i.e. Vasopressor Use) up to Day 30 | Up to Day 30 | The duration of septic shock was defined as the cumulative periods (\>1 h), from start of investigational medicinal product (IMP) treatment until Day 30, on IMP or vasopressors. |
| Duration of Mechanical Ventilation up to Day 30 | Up to Day 30 | The duration of mechanical ventilation was defined as the cumulative periods (\>1 h), from start of the IMP treatment until Day 30, on mechanical ventilation. |
| The Percentage of Subjects With RRT up to Day 30 (Counting Subjects Who Died as on RRT and Excluding Subjects on RRT for Chronic Renal Failure at the Time of Randomization) | Up to Day 30 | Renal replacement therapy is defined as continuous RRT, intermittent hemodialysis, or peritoneal dialysis. In order to ensure that any reduction in the incidence of RRT was not caused by an increase in mortality, all subjects dying within the 30-day period were counted as on RRT. |
| Duration of RRT up to Day 90 (Excluding Subjects on RRT for Chronic Failure at the Time of Randomization) | Up to Day 90 | The duration of RRT was defined as the cumulative periods (\>1 h) from start of IMP until Day 90 with RRT (continuous renal replacement therapy, intermittent hemodialysis, or peritoneal dialysis). Subjects on RRT for chronic renal failure at time of randomization were not included in the analysis. |
| All-cause Mortality | At Day 90 | All-cause mortality defined as the percentage of subjects that have died, regardless of cause. |
| Percentage of Subjects With New Organ Dysfunction and New Organ Failure (Based on the SOFA Score) up to Day 7 and Day 30 | Up to Day 7 and Day 30 | The presence of 5 organ dysfunctions (cardiovascular, respiratory, renal, hepatic, coagulation) was assessed using a SOFA score. Each organ has a possible dysfunction score of 0 (no organ dysfunction) to 4 (all organs with dysfunction). Incidence of new organ dysfunction is defined as an increase ≥ 1 from baseline to post baseline up until the end of the period (e.g. going from 1-2) in any of the individual SOFA scores. Incidence of new organ failures is defined as a change in any of the individual SOFA scores from (0-2) at baseline to (3-4) post baseline up until the end of the period (Day 7 or 30) (if the SOFA scores goes from (0-2) to (3-4) and back to (0-2) again within the period, that will still count as a new organ failure). Percentage of subjects with new organ dysfunction and new organ failure (based on the SOFA Score) up to Day 7 and Day 30 are reported. |
| ICU Length of Stay up to Day 30 | Up to Day 30 | ICU length of stay is defined as the cumulative periods (\>1 h) spent in ICU from start of IMP to 30 days after. |
| All-cause Mortality (Defined as the Percentage of Subjects That Have Died, Regardless of Cause) at Day 30 and Day 180 | At Day 30 and Day 180 | All-cause mortality defined as the percentage of subjects that have died, regardless of cause. |
| Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Baseline and Days 1-7 | Fluid balance (as a rate of time) calculated for fluid administered during episode of severe sepsis/septic shock will be presented until ICU discharge (for a maximum of 7 days). |
| Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Baseline and Days 1-7 | Cumulative fluid balance (total volume) calculated for fluid administered during episode of severe sepsis/septic shock will be presented until ICU discharge (for a maximum of 7 days). |
| Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Baseline and Days 1-7 | — |
| Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Baseline and Days 1-7 | Cumulative urinary output (absolute values) will be presented until ICU discharge (for a maximum of 7 Days). |
| Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | Baseline and Days 30, 60, 90 and 180 | The EuroQoL-5-Dimensions (EQ-5D™) was used to assess the overall health of each subject. EQ-5D™ is a standardised instrument for use as a measure of health outcome. The first part of the instrument includes 5 dimensions where the subject indicates which of the given statements best describes the health state on the day of questionnaire completion. The second part contains a visual analogue scale (VAS) where the subject indicates how good or bad his or her own health is on the day of questionnaire completion. EQ-5D-5L will be analyzed by the index value (Range: 0-1; 0=dead state, 1=full health state), the overall quality-adjusted life year (QALY), and the VAS score (Range: 0-100; 0=worst health state, 100=best health state). The EQ-5D-5L was completed at baseline and at the scheduled follow-up days (i.e. Day 30, Day 60, Day 90, and Day 180). Data for EQ VAS score and EQ-5D-5L index score are reported in this endpoint. |
| Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Days 1, 3, and 7 or discharge from ICU | The presence of 5 organ dysfunctions (cardiovascular, respiratory, renal, hepatic, coagulation) was assessed using a modified Sequential Organ Failure Assessment (SOFA) (i.e. SOFA except the Glasgow Coma Scale). In addition, any dose of vasopressors or positive ionotropes will attribute 3 or 2 points on the cardiovascular scale, respectively. Each organ has a possible dysfunction score of 0 (no organ dysfunction) to 4 (dysfunctional organ), for a total modified SOFA score range of 0 (no organ dysfunction) to 23 (all organs with dysfunction). |
Countries
Belgium, Denmark, France, Netherlands, United States
Participant flow
Recruitment details
A total of 63 sites were authorized to recruit subjects for the trial between July 2015 and August 2017. Eleven of these sites did not recruit any subjects. The trial sites that randomized subjects to the trial were: 11 in Belgium, 5 in Denmark, 17 in France, 5 in the Netherlands, and 14 in the United States of America (USA).
Pre-assignment details
A total of 6377 subjects were screened, of which 868 subjects were randomized (585 subjects were allocated to selepressin \[three doses\] and 283 subjects were allocated to placebo). Up to four dosing regimens of selepressin were planned to be investigated in the trial. However, the highest dosing regimen was not used.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Sterile 0.9% sodium chloride solution given as an infusion, was used as the placebo. | 266 |
| Selepressin 2.5 ng/kg/Min Starting dose: 1.7 ng/kg/min selepressin; Maximum dose: 2.5 ng/kg/min selepressin, given as an infusion. | 191 |
| Selepressin 3.75 ng/kg/Min Starting dose: 2.5 ng/kg/min selepressin; Maximum dose: 3.75 ng/kg/min selepressin, given as an infusion. | 177 |
| Selepressin 5.25 ng/kg/Min Starting dose: 3.5 ng/kg/min selepressin; Maximum dose: 5.25 ng/kg/min selepressin, given as an infusion. | 194 |
| Total | 828 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Investigator withdrew the subject | 1 | 2 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 | 0 | 1 |
| Overall Study | Post randomization screening failure | 12 | 4 | 9 | 3 |
| Overall Study | Withdrawal by Subject | 4 | 6 | 5 | 6 |
Baseline characteristics
| Characteristic | Placebo | Selepressin 2.5 ng/kg/Min | Selepressin 3.75 ng/kg/Min | Selepressin 5.25 ng/kg/Min | Total |
|---|---|---|---|---|---|
| Age, Continuous | 65.7 years STANDARD_DEVIATION 14.56 | 66.0 years STANDARD_DEVIATION 12.76 | 67.2 years STANDARD_DEVIATION 13.13 | 66.8 years STANDARD_DEVIATION 12.47 | 66.3 years STANDARD_DEVIATION 13.37 |
| Baseline BMI | 27.47 kg/m^2 STANDARD_DEVIATION 7.234 | 27.56 kg/m^2 STANDARD_DEVIATION 8.778 | 28.04 kg/m^2 STANDARD_DEVIATION 7.885 | 27.98 kg/m^2 STANDARD_DEVIATION 8.565 | 27.73 kg/m^2 STANDARD_DEVIATION 8.055 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 3 Participants | 1 Participants | 4 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 262 Participants | 188 Participants | 176 Participants | 190 Participants | 816 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 5 Participants | 4 Participants | 12 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 3 Participants | 11 Participants | 7 Participants | 25 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 260 Participants | 186 Participants | 161 Participants | 183 Participants | 790 Participants |
| Sex: Female, Male Female | 121 Participants | 80 Participants | 70 Participants | 70 Participants | 341 Participants |
| Sex: Female, Male Male | 145 Participants | 111 Participants | 107 Participants | 124 Participants | 487 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 116 / 266 | 80 / 191 | 76 / 177 | 85 / 194 | 241 / 562 |
| other Total, other adverse events | 94 / 266 | 54 / 191 | 63 / 177 | 60 / 194 | 177 / 562 |
| serious Total, serious adverse events | 85 / 266 | 57 / 191 | 65 / 177 | 57 / 194 | 179 / 562 |
Outcome results
Primary
Vasopressor- and Mechanical Ventilator-free Days (PVFDs)
Composite endpoint defined as number of days from start of treatment to 30 days thereafter during which subject is: 1. Alive. However, if patient dies within these 30-days then PVFDs will be zero even if there is a period during which subject is alive and free of both vasopressor treatment and mechanical ventilation; 2. Free of treatment with vasopressors: Less than 60 min during any contiguous 24-h period. If a patient requires vasopressors longer than 60 min in total during any 24-h period, the intervening intervals during which they are free of vasopressors will not be included in the determination of PVFDs; 3. Free of any mechanical ventilation: Less than 60 min during any contiguous 24-h period. If a patient requires mechanical ventilation longer than 60 min in total during any 24-h period, the intervening intervals during which they are not receiving mechanical ventilation will not be included in the period free of mechanical ventilation in the determination of PVFDs.
Time frame: Up to Day 30
Population: The FAS comprised of all subjects who were enrolled (i.e. randomized \[as planned\]) and dosed. The primary comparison to determine statistical and clinical significance was between all subjects in all selepressin arms (pooled together and treated as a single arm) and all subjects in the placebo arm, to control Type 1 error.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Vasopressor- and Mechanical Ventilator-free Days (PVFDs) | 14.45 days |
| Selepressin Pooled | Vasopressor- and Mechanical Ventilator-free Days (PVFDs) | 15.00 days |
Comparison: The primary endpoint was analyzed using a van Elteren test. The analysis included a test of superiority using a two-sided 5% significance level.p-value: 0.301595% CI: [-1.34, 2.43]van Elteren test
Secondary
All-cause Mortality
All-cause mortality defined as the percentage of subjects that have died, regardless of cause.
Time frame: At Day 90
Population: The FAS comprised of all subjects who were enrolled (i.e. randomized \[as planned\]) and dosed. The primary comparison to determine statistical and clinical significance was between all subjects in all selepressin arms (pooled together and treated as a single arm) and all subjects in the placebo arm, to control Type 1 error.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | All-cause Mortality | 39.44 percentage of subjects |
| Selepressin Pooled | All-cause Mortality | 40.59 percentage of subjects |
Comparison: Mortality was analyzed using a logistic regression model with the individual sequential organ failure assessment (SOFA) scores and age as covariates and treatment arm as factor.p-value: 0.769495% CI: [0.762, 1.445]Regression, Logistic
Secondary
All-cause Mortality (Defined as the Percentage of Subjects That Have Died, Regardless of Cause) at Day 30 and Day 180
All-cause mortality defined as the percentage of subjects that have died, regardless of cause.
Time frame: At Day 30 and Day 180
Population: The FAS comprised of all subjects who were enrolled (i.e. randomized \[as planned\]) and dosed.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Placebo | All-cause Mortality (Defined as the Percentage of Subjects That Have Died, Regardless of Cause) at Day 30 and Day 180 | Day 30 | Yes | 91 Participants |
| Placebo | All-cause Mortality (Defined as the Percentage of Subjects That Have Died, Regardless of Cause) at Day 30 and Day 180 | Day 180 | Yes | 116 Participants |
| Placebo | All-cause Mortality (Defined as the Percentage of Subjects That Have Died, Regardless of Cause) at Day 30 and Day 180 | Day 30 | No | 174 Participants |
| Placebo | All-cause Mortality (Defined as the Percentage of Subjects That Have Died, Regardless of Cause) at Day 30 and Day 180 | Day 180 | No | 147 Participants |
| Selepressin Pooled | All-cause Mortality (Defined as the Percentage of Subjects That Have Died, Regardless of Cause) at Day 30 and Day 180 | Day 30 | No | 121 Participants |
| Selepressin Pooled | All-cause Mortality (Defined as the Percentage of Subjects That Have Died, Regardless of Cause) at Day 30 and Day 180 | Day 180 | Yes | 80 Participants |
| Selepressin Pooled | All-cause Mortality (Defined as the Percentage of Subjects That Have Died, Regardless of Cause) at Day 30 and Day 180 | Day 30 | Yes | 66 Participants |
| Selepressin Pooled | All-cause Mortality (Defined as the Percentage of Subjects That Have Died, Regardless of Cause) at Day 30 and Day 180 | Day 180 | No | 104 Participants |
| Selepressin 3.75 ng/kg/Min | All-cause Mortality (Defined as the Percentage of Subjects That Have Died, Regardless of Cause) at Day 30 and Day 180 | Day 180 | Yes | 76 Participants |
| Selepressin 3.75 ng/kg/Min | All-cause Mortality (Defined as the Percentage of Subjects That Have Died, Regardless of Cause) at Day 30 and Day 180 | Day 180 | No | 96 Participants |
| Selepressin 3.75 ng/kg/Min | All-cause Mortality (Defined as the Percentage of Subjects That Have Died, Regardless of Cause) at Day 30 and Day 180 | Day 30 | No | 114 Participants |
| Selepressin 3.75 ng/kg/Min | All-cause Mortality (Defined as the Percentage of Subjects That Have Died, Regardless of Cause) at Day 30 and Day 180 | Day 30 | Yes | 62 Participants |
| Selepressin 5.25 ng/kg/Min | All-cause Mortality (Defined as the Percentage of Subjects That Have Died, Regardless of Cause) at Day 30 and Day 180 | Day 180 | Yes | 85 Participants |
| Selepressin 5.25 ng/kg/Min | All-cause Mortality (Defined as the Percentage of Subjects That Have Died, Regardless of Cause) at Day 30 and Day 180 | Day 180 | No | 102 Participants |
| Selepressin 5.25 ng/kg/Min | All-cause Mortality (Defined as the Percentage of Subjects That Have Died, Regardless of Cause) at Day 30 and Day 180 | Day 30 | Yes | 65 Participants |
| Selepressin 5.25 ng/kg/Min | All-cause Mortality (Defined as the Percentage of Subjects That Have Died, Regardless of Cause) at Day 30 and Day 180 | Day 30 | No | 124 Participants |
| Selepressin Pooled | All-cause Mortality (Defined as the Percentage of Subjects That Have Died, Regardless of Cause) at Day 30 and Day 180 | Day 30 | No | 359 Participants |
| Selepressin Pooled | All-cause Mortality (Defined as the Percentage of Subjects That Have Died, Regardless of Cause) at Day 30 and Day 180 | Day 180 | Yes | 241 Participants |
| Selepressin Pooled | All-cause Mortality (Defined as the Percentage of Subjects That Have Died, Regardless of Cause) at Day 30 and Day 180 | Day 180 | No | 302 Participants |
| Selepressin Pooled | All-cause Mortality (Defined as the Percentage of Subjects That Have Died, Regardless of Cause) at Day 30 and Day 180 | Day 30 | Yes | 193 Participants |
Secondary
Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days)
Cumulative fluid balance (total volume) calculated for fluid administered during episode of severe sepsis/septic shock will be presented until ICU discharge (for a maximum of 7 days).
Time frame: Baseline and Days 1-7
Population: The FAS comprised of all subjects who were enrolled (i.e. randomized \[as planned\]) and dosed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 3 | 4179.02 mL | Standard Deviation 5054.24 |
| Placebo | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 2 | 3688.96 mL | Standard Deviation 4071.55 |
| Placebo | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 7 | 4978.66 mL | Standard Deviation 7803.61 |
| Placebo | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 6 | 4750.10 mL | Standard Deviation 7322.08 |
| Placebo | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 1 | 2513.84 mL | Standard Deviation 2649.6 |
| Placebo | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Baseline | 3715.19 mL | Standard Deviation 2191.23 |
| Placebo | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 5 | 4600.67 mL | Standard Deviation 6723.02 |
| Placebo | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 4 | 4347.58 mL | Standard Deviation 6027.04 |
| Selepressin Pooled | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Baseline | 4043.77 mL | Standard Deviation 2650.73 |
| Selepressin Pooled | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 1 | 2283.24 mL | Standard Deviation 2805.64 |
| Selepressin Pooled | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 2 | 3470.11 mL | Standard Deviation 4148.24 |
| Selepressin Pooled | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 3 | 4020.24 mL | Standard Deviation 4939.49 |
| Selepressin Pooled | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 5 | 4307.39 mL | Standard Deviation 5636.37 |
| Selepressin Pooled | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 6 | 4312.81 mL | Standard Deviation 6564.9 |
| Selepressin Pooled | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 7 | 4418.66 mL | Standard Deviation 7263.42 |
| Selepressin Pooled | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 4 | 4094.19 mL | Standard Deviation 5122.49 |
| Selepressin 3.75 ng/kg/Min | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 3 | 3684.97 mL | Standard Deviation 4584.27 |
| Selepressin 3.75 ng/kg/Min | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 1 | 2083.09 mL | Standard Deviation 2684.72 |
| Selepressin 3.75 ng/kg/Min | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 5 | 5126.22 mL | Standard Deviation 6910.78 |
| Selepressin 3.75 ng/kg/Min | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 4 | 4633.22 mL | Standard Deviation 5855.47 |
| Selepressin 3.75 ng/kg/Min | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 6 | 5263.21 mL | Standard Deviation 7595.18 |
| Selepressin 3.75 ng/kg/Min | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 7 | 5628.59 mL | Standard Deviation 8471.78 |
| Selepressin 3.75 ng/kg/Min | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 2 | 3114.71 mL | Standard Deviation 3588.75 |
| Selepressin 3.75 ng/kg/Min | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Baseline | 4250.88 mL | Standard Deviation 2943.81 |
| Selepressin 5.25 ng/kg/Min | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 6 | 4224.47 mL | Standard Deviation 7163.95 |
| Selepressin 5.25 ng/kg/Min | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 3 | 3212.04 mL | Standard Deviation 4932.67 |
| Selepressin 5.25 ng/kg/Min | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 2 | 2584.89 mL | Standard Deviation 3621.66 |
| Selepressin 5.25 ng/kg/Min | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 1 | 1600.21 mL | Standard Deviation 2326.52 |
| Selepressin 5.25 ng/kg/Min | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 7 | 4425.98 mL | Standard Deviation 7977.33 |
| Selepressin 5.25 ng/kg/Min | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Baseline | 3874.96 mL | Standard Deviation 2499.8 |
| Selepressin 5.25 ng/kg/Min | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 4 | 3880.32 mL | Standard Deviation 5643.93 |
| Selepressin 5.25 ng/kg/Min | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 5 | 4079.52 mL | Standard Deviation 6367.01 |
| Selepressin Pooled | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 2 | 3049.40 mL | Standard Deviation 3809.45 |
| Selepressin Pooled | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Baseline | 4050.78 mL | Standard Deviation 2696.92 |
| Selepressin Pooled | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 1 | 1984.43 mL | Standard Deviation 2621.8 |
| Selepressin Pooled | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 6 | 4582.04 mL | Standard Deviation 7121.18 |
| Selepressin Pooled | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 5 | 4497.16 mL | Standard Deviation 6342.44 |
| Selepressin Pooled | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 3 | 3630.48 mL | Standard Deviation 4825.32 |
| Selepressin Pooled | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 4 | 4195.31 mL | Standard Deviation 5546.47 |
| Selepressin Pooled | Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 7 | 4814.08 mL | Standard Deviation 7919.51 |
Secondary
Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days)
Cumulative urinary output (absolute values) will be presented until ICU discharge (for a maximum of 7 Days).
Time frame: Baseline and Days 1-7
Population: The FAS comprised of all subjects who were enrolled (i.e. randomized \[as planned\]) and dosed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Baseline | 888.834 mL | Standard Deviation 1197.4426 |
| Placebo | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 1 | 2046.658 mL | Standard Deviation 1687.7381 |
| Placebo | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 2 | 4343.786 mL | Standard Deviation 2909.9212 |
| Placebo | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 3 | 6885.176 mL | Standard Deviation 4100.2125 |
| Placebo | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 4 | 9501.722 mL | Standard Deviation 5247.553 |
| Placebo | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 5 | 12600.503 mL | Standard Deviation 6293.7322 |
| Placebo | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 6 | 15159.980 mL | Standard Deviation 7264.4502 |
| Placebo | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 7 | 17817.979 mL | Standard Deviation 8226.0238 |
| Selepressin Pooled | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 2 | 4702.538 mL | Standard Deviation 3199.5558 |
| Selepressin Pooled | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 5 | 13219.597 mL | Standard Deviation 6695.6766 |
| Selepressin Pooled | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Baseline | 898.056 mL | Standard Deviation 1020.789 |
| Selepressin Pooled | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 3 | 7527.805 mL | Standard Deviation 4401.3731 |
| Selepressin Pooled | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 1 | 2430.485 mL | Standard Deviation 1929.94 |
| Selepressin Pooled | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 7 | 19269.682 mL | Standard Deviation 9081.2013 |
| Selepressin Pooled | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 4 | 10239.275 mL | Standard Deviation 5486.118 |
| Selepressin Pooled | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 6 | 16354.712 mL | Standard Deviation 7864.2281 |
| Selepressin 3.75 ng/kg/Min | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 6 | 14522.098 mL | Standard Deviation 7391.7707 |
| Selepressin 3.75 ng/kg/Min | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 7 | 17034.774 mL | Standard Deviation 8635.0531 |
| Selepressin 3.75 ng/kg/Min | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 3 | 6587.704 mL | Standard Deviation 3849.2099 |
| Selepressin 3.75 ng/kg/Min | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 5 | 11132.418 mL | Standard Deviation 6230.4688 |
| Selepressin 3.75 ng/kg/Min | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 2 | 4534.714 mL | Standard Deviation 2825.174 |
| Selepressin 3.75 ng/kg/Min | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 1 | 2262.948 mL | Standard Deviation 1703.529 |
| Selepressin 3.75 ng/kg/Min | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Baseline | 947.843 mL | Standard Deviation 1264.9054 |
| Selepressin 3.75 ng/kg/Min | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 4 | 8786.522 mL | Standard Deviation 5086.7347 |
| Selepressin 5.25 ng/kg/Min | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 1 | 2497.173 mL | Standard Deviation 1821.3014 |
| Selepressin 5.25 ng/kg/Min | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 2 | 4814.544 mL | Standard Deviation 3091.735 |
| Selepressin 5.25 ng/kg/Min | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 3 | 7322.964 mL | Standard Deviation 4322.9651 |
| Selepressin 5.25 ng/kg/Min | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 4 | 9851.841 mL | Standard Deviation 5478.3671 |
| Selepressin 5.25 ng/kg/Min | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 5 | 12795.773 mL | Standard Deviation 6400.6821 |
| Selepressin 5.25 ng/kg/Min | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 7 | 18380.119 mL | Standard Deviation 8479.7547 |
| Selepressin 5.25 ng/kg/Min | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Baseline | 1017.646 mL | Standard Deviation 1076.2691 |
| Selepressin 5.25 ng/kg/Min | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 6 | 15674.783 mL | Standard Deviation 7202.3158 |
| Selepressin Pooled | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 3 | 7150.914 mL | Standard Deviation 4211.3049 |
| Selepressin Pooled | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 7 | 18222.202 mL | Standard Deviation 8736.1728 |
| Selepressin Pooled | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 2 | 4689.788 mL | Standard Deviation 3045.8065 |
| Selepressin Pooled | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 6 | 15514.875 mL | Standard Deviation 7479.2644 |
| Selepressin Pooled | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Baseline | 955.426 mL | Standard Deviation 1121.3215 |
| Selepressin Pooled | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 5 | 12372.680 mL | Standard Deviation 6480.0818 |
| Selepressin Pooled | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 1 | 2400.740 mL | Standard Deviation 1822.8019 |
| Selepressin Pooled | Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 4 | 9630.976 mL | Standard Deviation 5377.6356 |
Secondary
Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days)
Fluid balance (as a rate of time) calculated for fluid administered during episode of severe sepsis/septic shock will be presented until ICU discharge (for a maximum of 7 days).
Time frame: Baseline and Days 1-7
Population: The FAS comprised of all subjects who were enrolled (i.e. randomized \[as planned\]) and dosed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 5 | -0.30 mL/h | Standard Deviation 72.84 |
| Placebo | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 3 | 19.71 mL/h | Standard Deviation 79.94 |
| Placebo | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 6 | -4.70 mL/h | Standard Deviation 61.16 |
| Placebo | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 4 | 2.34 mL/h | Standard Deviation 75.41 |
| Placebo | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 1 | 104.74 mL/h | Standard Deviation 110.4 |
| Placebo | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Baseline | 339.10 mL/h | Standard Deviation 236.53 |
| Placebo | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 2 | 51.78 mL/h | Standard Deviation 79.27 |
| Placebo | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 7 | -5.84 mL/h | Standard Deviation 62.52 |
| Selepressin Pooled | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 3 | 24.87 mL/h | Standard Deviation 65.2 |
| Selepressin Pooled | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Baseline | 342.23 mL/h | Standard Deviation 218.17 |
| Selepressin Pooled | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 4 | 6.76 mL/h | Standard Deviation 59.14 |
| Selepressin Pooled | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 1 | 95.14 mL/h | Standard Deviation 116.9 |
| Selepressin Pooled | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 7 | -7.36 mL/h | Standard Deviation 63.51 |
| Selepressin Pooled | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 6 | -12.19 mL/h | Standard Deviation 80.3 |
| Selepressin Pooled | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 5 | 1.08 mL/h | Standard Deviation 62.02 |
| Selepressin Pooled | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 2 | 52.75 mL/h | Standard Deviation 74.12 |
| Selepressin 3.75 ng/kg/Min | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 4 | 22.28 mL/h | Standard Deviation 70.95 |
| Selepressin 3.75 ng/kg/Min | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 1 | 86.80 mL/h | Standard Deviation 111.86 |
| Selepressin 3.75 ng/kg/Min | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 5 | 5.94 mL/h | Standard Deviation 71.72 |
| Selepressin 3.75 ng/kg/Min | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 6 | -3.49 mL/h | Standard Deviation 75.52 |
| Selepressin 3.75 ng/kg/Min | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 7 | 4.17 mL/h | Standard Deviation 67.38 |
| Selepressin 3.75 ng/kg/Min | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Baseline | 365.14 mL/h | Standard Deviation 255.92 |
| Selepressin 3.75 ng/kg/Min | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 2 | 48.95 mL/h | Standard Deviation 65.47 |
| Selepressin 3.75 ng/kg/Min | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 3 | 33.34 mL/h | Standard Deviation 67.61 |
| Selepressin 5.25 ng/kg/Min | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 6 | -5.91 mL/h | Standard Deviation 64.72 |
| Selepressin 5.25 ng/kg/Min | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 5 | 3.06 mL/h | Standard Deviation 62.49 |
| Selepressin 5.25 ng/kg/Min | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 3 | 29.14 mL/h | Standard Deviation 75.19 |
| Selepressin 5.25 ng/kg/Min | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 4 | 19.50 mL/h | Standard Deviation 66.09 |
| Selepressin 5.25 ng/kg/Min | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 2 | 44.35 mL/h | Standard Deviation 73.82 |
| Selepressin 5.25 ng/kg/Min | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 1 | 66.68 mL/h | Standard Deviation 96.94 |
| Selepressin 5.25 ng/kg/Min | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Baseline | 350.51 mL/h | Standard Deviation 278.28 |
| Selepressin 5.25 ng/kg/Min | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 7 | -12.71 mL/h | Standard Deviation 58.19 |
| Selepressin Pooled | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Baseline | 352.38 mL/h | Standard Deviation 252.01 |
| Selepressin Pooled | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 1 | 82.68 mL/h | Standard Deviation 109.24 |
| Selepressin Pooled | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 6 | -7.05 mL/h | Standard Deviation 73.03 |
| Selepressin Pooled | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 2 | 48.62 mL/h | Standard Deviation 71.39 |
| Selepressin Pooled | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 5 | 3.41 mL/h | Standard Deviation 65.4 |
| Selepressin Pooled | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 7 | -5.55 mL/h | Standard Deviation 63.12 |
| Selepressin Pooled | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 4 | 16.25 mL/h | Standard Deviation 65.76 |
| Selepressin Pooled | Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days) | Day 3 | 29.11 mL/h | Standard Deviation 69.52 |
Secondary
Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days)
Time frame: Baseline and Days 1-7
Population: The FAS comprised of all subjects who were enrolled (i.e. randomized \[as planned\]) and dosed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 7 | 116.082 mL/h | Standard Deviation 65.9402 |
| Placebo | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 3 | 104.124 mL/h | Standard Deviation 67.7586 |
| Placebo | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Baseline | 73.726 mL/h | Standard Deviation 94.7641 |
| Placebo | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 1 | 85.277 mL/h | Standard Deviation 70.3224 |
| Placebo | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 2 | 88.425 mL/h | Standard Deviation 61.2134 |
| Placebo | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 5 | 116.732 mL/h | Standard Deviation 65.1159 |
| Placebo | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 4 | 110.078 mL/h | Standard Deviation 73.3563 |
| Placebo | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 6 | 119.087 mL/h | Standard Deviation 65.7102 |
| Selepressin Pooled | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 4 | 103.459 mL/h | Standard Deviation 69.8165 |
| Selepressin Pooled | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 6 | 126.512 mL/h | Standard Deviation 83.3418 |
| Selepressin Pooled | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 5 | 110.129 mL/h | Standard Deviation 65.7571 |
| Selepressin Pooled | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 7 | 121.751 mL/h | Standard Deviation 68.1265 |
| Selepressin Pooled | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 1 | 101.270 mL/h | Standard Deviation 80.4142 |
| Selepressin Pooled | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 2 | 89.404 mL/h | Standard Deviation 64.9307 |
| Selepressin Pooled | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Baseline | 72.944 mL/h | Standard Deviation 82.3338 |
| Selepressin Pooled | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 3 | 104.833 mL/h | Standard Deviation 66.4533 |
| Selepressin 3.75 ng/kg/Min | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 2 | 88.210 mL/h | Standard Deviation 59.6632 |
| Selepressin 3.75 ng/kg/Min | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 5 | 100.581 mL/h | Standard Deviation 75.5667 |
| Selepressin 3.75 ng/kg/Min | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 3 | 85.403 mL/h | Standard Deviation 61.566 |
| Selepressin 3.75 ng/kg/Min | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Baseline | 74.530 mL/h | Standard Deviation 92.8984 |
| Selepressin 3.75 ng/kg/Min | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 6 | 116.799 mL/h | Standard Deviation 79.3092 |
| Selepressin 3.75 ng/kg/Min | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 7 | 111.499 mL/h | Standard Deviation 72.8493 |
| Selepressin 3.75 ng/kg/Min | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 1 | 94.290 mL/h | Standard Deviation 70.9804 |
| Selepressin 3.75 ng/kg/Min | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 4 | 92.311 mL/h | Standard Deviation 65.0558 |
| Selepressin 5.25 ng/kg/Min | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 7 | 114.284 mL/h | Standard Deviation 69.5828 |
| Selepressin 5.25 ng/kg/Min | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 3 | 97.312 mL/h | Standard Deviation 67.8895 |
| Selepressin 5.25 ng/kg/Min | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 5 | 117.152 mL/h | Standard Deviation 68.3988 |
| Selepressin 5.25 ng/kg/Min | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 2 | 92.400 mL/h | Standard Deviation 61.8536 |
| Selepressin 5.25 ng/kg/Min | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 4 | 102.859 mL/h | Standard Deviation 64.2044 |
| Selepressin 5.25 ng/kg/Min | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Baseline | 83.773 mL/h | Standard Deviation 86.5417 |
| Selepressin 5.25 ng/kg/Min | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 6 | 118.269 mL/h | Standard Deviation 72.291 |
| Selepressin 5.25 ng/kg/Min | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 1 | 104.049 mL/h | Standard Deviation 75.8876 |
| Selepressin Pooled | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 5 | 109.494 mL/h | Standard Deviation 70.2288 |
| Selepressin Pooled | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 2 | 90.085 mL/h | Standard Deviation 62.1593 |
| Selepressin Pooled | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 3 | 95.902 mL/h | Standard Deviation 65.7529 |
| Selepressin Pooled | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 6 | 120.311 mL/h | Standard Deviation 77.8633 |
| Selepressin Pooled | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 7 | 115.720 mL/h | Standard Deviation 70.0786 |
| Selepressin Pooled | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Baseline | 77.212 mL/h | Standard Deviation 87.2301 |
| Selepressin Pooled | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 1 | 100.031 mL/h | Standard Deviation 75.9501 |
| Selepressin Pooled | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | Day 4 | 99.618 mL/h | Standard Deviation 66.3843 |
Secondary
Duration of Mechanical Ventilation up to Day 30
The duration of mechanical ventilation was defined as the cumulative periods (\>1 h), from start of the IMP treatment until Day 30, on mechanical ventilation.
Time frame: Up to Day 30
Population: The FAS comprised of all subjects who were enrolled (i.e. randomized \[as planned\]) and dosed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Duration of Mechanical Ventilation up to Day 30 | 2.255 days |
| Selepressin Pooled | Duration of Mechanical Ventilation up to Day 30 | 1.690 days |
| Selepressin 3.75 ng/kg/Min | Duration of Mechanical Ventilation up to Day 30 | 2.800 days |
| Selepressin 5.25 ng/kg/Min | Duration of Mechanical Ventilation up to Day 30 | 1.910 days |
| Selepressin Pooled | Duration of Mechanical Ventilation up to Day 30 | 1.990 days |
Secondary
Duration of RRT up to Day 90 (Excluding Subjects on RRT for Chronic Failure at the Time of Randomization)
The duration of RRT was defined as the cumulative periods (\>1 h) from start of IMP until Day 90 with RRT (continuous renal replacement therapy, intermittent hemodialysis, or peritoneal dialysis). Subjects on RRT for chronic renal failure at time of randomization were not included in the analysis.
Time frame: Up to Day 90
Population: The FAS comprised of all subjects who were enrolled (i.e. randomized \[as planned\]) and dosed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Duration of RRT up to Day 90 (Excluding Subjects on RRT for Chronic Failure at the Time of Randomization) | 1.634 days | Standard Deviation 5.538 |
| Selepressin Pooled | Duration of RRT up to Day 90 (Excluding Subjects on RRT for Chronic Failure at the Time of Randomization) | 1.739 days | Standard Deviation 5.5593 |
| Selepressin 3.75 ng/kg/Min | Duration of RRT up to Day 90 (Excluding Subjects on RRT for Chronic Failure at the Time of Randomization) | 1.876 days | Standard Deviation 6.03 |
| Selepressin 5.25 ng/kg/Min | Duration of RRT up to Day 90 (Excluding Subjects on RRT for Chronic Failure at the Time of Randomization) | 2.459 days | Standard Deviation 10.1365 |
| Selepressin Pooled | Duration of RRT up to Day 90 (Excluding Subjects on RRT for Chronic Failure at the Time of Randomization) | 2.030 days | Standard Deviation 7.564 |
Secondary
Duration of Septic Shock (i.e. Vasopressor Use) up to Day 30
The duration of septic shock was defined as the cumulative periods (\>1 h), from start of investigational medicinal product (IMP) treatment until Day 30, on IMP or vasopressors.
Time frame: Up to Day 30
Population: The FAS comprised of all subjects who were enrolled (i.e. randomized \[as planned\]) and dosed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Duration of Septic Shock (i.e. Vasopressor Use) up to Day 30 | 2.220 days |
| Selepressin Pooled | Duration of Septic Shock (i.e. Vasopressor Use) up to Day 30 | 1.660 days |
| Selepressin 3.75 ng/kg/Min | Duration of Septic Shock (i.e. Vasopressor Use) up to Day 30 | 1.790 days |
| Selepressin 5.25 ng/kg/Min | Duration of Septic Shock (i.e. Vasopressor Use) up to Day 30 | 1.465 days |
| Selepressin Pooled | Duration of Septic Shock (i.e. Vasopressor Use) up to Day 30 | 1.635 days |
Secondary
ICU Length of Stay up to Day 30
ICU length of stay is defined as the cumulative periods (\>1 h) spent in ICU from start of IMP to 30 days after.
Time frame: Up to Day 30
Population: The FAS comprised of all subjects who were enrolled (i.e. randomized \[as planned\]) and dosed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | ICU Length of Stay up to Day 30 | 6.755 days |
| Selepressin Pooled | ICU Length of Stay up to Day 30 | 4.940 days |
| Selepressin 3.75 ng/kg/Min | ICU Length of Stay up to Day 30 | 6.460 days |
| Selepressin 5.25 ng/kg/Min | ICU Length of Stay up to Day 30 | 5.960 days |
| Selepressin Pooled | ICU Length of Stay up to Day 30 | 5.695 days |
Secondary
Intensive Care Unit (ICU)-Free Days
The ICU free days, as for the PVFDs, reflect the time from last discharge of the ICU to Day 30 with an absolute penalty for mortality, i.e., any subject that died within this 30-day period was assigned zero value).
Time frame: Up to Day 30
Population: The FAS comprised of all subjects who were enrolled (i.e. randomized \[as planned\]) and dosed. The primary comparison to determine statistical and clinical significance was between all subjects in all selepressin arms (pooled together and treated as a single arm) and all subjects in the placebo arm, to control Type 1 error.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Intensive Care Unit (ICU)-Free Days | 12.15 days |
| Selepressin Pooled | Intensive Care Unit (ICU)-Free Days | 12.64 days |
Comparison: This endpoint was analyzed using a van Elteren test. The analysis was a test of superiority using a two-sided 5% significance level.p-value: 0.412495% CI: [-1.22, 2.19]van Elteren test
Secondary
Mechanical Ventilator-free Days up to Day 30
Number of days from start of treatment to 30 days thereafter during which the subject is free of any mechanical ventilation, i.e. less than 60 min during any contiguous 24-h period.
Time frame: Up to Day 30
Population: The FAS comprised of all subjects who were enrolled (i.e. randomized \[as planned\]) and dosed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Mechanical Ventilator-free Days up to Day 30 | 19.80 days |
| Selepressin Pooled | Mechanical Ventilator-free Days up to Day 30 | 18.90 days |
| Selepressin 3.75 ng/kg/Min | Mechanical Ventilator-free Days up to Day 30 | 17.20 days |
| Selepressin 5.25 ng/kg/Min | Mechanical Ventilator-free Days up to Day 30 | 17.50 days |
| Selepressin Pooled | Mechanical Ventilator-free Days up to Day 30 | 17.50 days |
Secondary
Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge
The presence of 5 organ dysfunctions (cardiovascular, respiratory, renal, hepatic, coagulation) was assessed using a modified Sequential Organ Failure Assessment (SOFA) (i.e. SOFA except the Glasgow Coma Scale). In addition, any dose of vasopressors or positive ionotropes will attribute 3 or 2 points on the cardiovascular scale, respectively. Each organ has a possible dysfunction score of 0 (no organ dysfunction) to 4 (dysfunctional organ), for a total modified SOFA score range of 0 (no organ dysfunction) to 23 (all organs with dysfunction).
Time frame: Days 1, 3, and 7 or discharge from ICU
Population: The FAS comprised of all subjects who were enrolled (i.e. randomized \[as planned\]) and dosed. The primary comparison to determine statistical and clinical significance was between all subjects in all selepressin arms (pooled together and treated as a single arm) and all subjects in the placebo arm, to control Type 1 error.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Liver) score Day 7 | 1.17 score on a scale |
| Placebo | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Respiratory) score Day 7 | 2.38 score on a scale |
| Placebo | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Cardiovascular) score Day 1 | 3.66 score on a scale |
| Placebo | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Cardiovascular) score Day 3 | 2.33 score on a scale |
| Placebo | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Renal) score Day 3 | 1.52 score on a scale |
| Placebo | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Renal) score Day 7 | 1.46 score on a scale |
| Placebo | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Coagulation) score Day 3 | 1.50 score on a scale |
| Placebo | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Coagulation) score Day 7 | 1.30 score on a scale |
| Placebo | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Liver) score Day 3 | 1.11 score on a scale |
| Placebo | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Overall score (Day 1) | 9.95 score on a scale |
| Placebo | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Overall score (Day 3) | 8.95 score on a scale |
| Placebo | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Overall score (Day 7) | 8.08 score on a scale |
| Placebo | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Respiratory) score Day 1 | 2.58 score on a scale |
| Placebo | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Respiratory) score Day 3 | 2.43 score on a scale |
| Placebo | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Cardiovascular) score Day 7 | 1.79 score on a scale |
| Placebo | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Renal) score Day 1 | 1.64 score on a scale |
| Placebo | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Coagulation) score Day 1 | 1.15 score on a scale |
| Placebo | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Liver) score Day 1 | 0.87 score on a scale |
| Selepressin Pooled | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Cardiovascular) score Day 1 | 3.23 score on a scale |
| Selepressin Pooled | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Overall score (Day 1) | 9.44 score on a scale |
| Selepressin Pooled | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Respiratory) score Day 7 | 2.41 score on a scale |
| Selepressin Pooled | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Coagulation) score Day 3 | 1.73 score on a scale |
| Selepressin Pooled | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Overall score (Day 3) | 9.06 score on a scale |
| Selepressin Pooled | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Cardiovascular) score Day 3 | 2.08 score on a scale |
| Selepressin Pooled | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Renal) score Day 1 | 1.59 score on a scale |
| Selepressin Pooled | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Cardiovascular) score Day 7 | 1.65 score on a scale |
| Selepressin Pooled | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Renal) score Day 3 | 1.61 score on a scale |
| Selepressin Pooled | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Overall score (Day 7) | 8.63 score on a scale |
| Selepressin Pooled | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Renal) score Day 7 | 1.63 score on a scale |
| Selepressin Pooled | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Coagulation) score Day 1 | 1.27 score on a scale |
| Selepressin Pooled | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Respiratory) score Day 3 | 2.40 score on a scale |
| Selepressin Pooled | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Respiratory) score Day 1 | 2.50 score on a scale |
| Selepressin Pooled | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Coagulation) score Day 7 | 1.53 score on a scale |
| Selepressin Pooled | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Liver) score Day 1 | 0.72 score on a scale |
| Selepressin Pooled | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Liver) score Day 3 | 1.07 score on a scale |
| Selepressin Pooled | Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge | Individual (Liver) score Day 7 | 1.35 score on a scale |
Comparison: Overall score using a modified version of the SOFA on Day 1p-value: 0.200995% CI: [-1.3, 0.27]ANCOVA
Comparison: Overall score using a modified version of the SOFA on Day 3p-value: 0.789495% CI: [-0.68, 0.9]ANCOVA
Comparison: Overall score using a modified version of the SOFA on Day 7p-value: 0.188895% CI: [-0.27, 1.37]ANCOVA
Comparison: Individual organ (respiratory) score using a modified version of the SOFA on Day 1p-value: 0.299795% CI: [-0.24, 0.07]ANCOVA
Comparison: Individual organ (respiratory) score using a modified version of the SOFA on Day 3p-value: 0.679695% CI: [-0.19, 0.12]ANCOVA
Comparison: Individual organ (respiratory) score using a modified version of the SOFA on Day 7p-value: 0.746795% CI: [-0.14, 0.19]ANCOVA
Comparison: Individual organ (cardiovascular) score using a modified version of the SOFA on Day 1p-value: 0.000395% CI: [-0.65, -0.19]ANCOVA
Comparison: Individual organ (cardiovascular) score using a modified version of the SOFA on Day 3p-value: 0.034995% CI: [-0.49, -0.02]ANCOVA
Comparison: Individual organ (cardiovascular) score using a modified version of the SOFA on Day 7p-value: 0.278795% CI: [-0.39, 0.11]ANCOVA
Comparison: Individual organ (renal) score using a modified version of the SOFA on Day 1p-value: 0.647695% CI: [-0.26, 0.16]ANCOVA
Comparison: Individual organ (renal) score using a modified version of the SOFA on Day 3p-value: 0.431395% CI: [-0.13, 0.29]ANCOVA
Comparison: Individual organ (renal) score using a modified version of the SOFA on Day 7p-value: 0.133495% CI: [-0.05, 0.39]ANCOVA
Comparison: Individual organ (coagulation) score using a modified version of the SOFA on Day 1p-value: 0.212695% CI: [-0.07, 0.3]ANCOVA
Comparison: Individual organ (coagulation) score using a modified version of the SOFA on Day 3p-value: 0.017495% CI: [0.04, 0.41]ANCOVA
Comparison: Individual organ (coagulation) score using a modified version of the SOFA on Day 7p-value: 0.019495% CI: [0.04, 0.43]ANCOVA
Comparison: Individual organ (liver) score using a modified version of the SOFA on Day 1p-value: 0.128495% CI: [-0.35, 0.04]ANCOVA
Comparison: Individual organ (liver) score using a modified version of the SOFA on Day 3p-value: 0.654295% CI: [-0.25, 0.15]ANCOVA
Comparison: Individual organ (liver) score using a modified version of the SOFA on Day 7p-value: 0.107995% CI: [-0.04, 0.38]ANCOVA
Secondary
Percentage of Subjects With New Organ Dysfunction and New Organ Failure (Based on the SOFA Score) up to Day 7 and Day 30
The presence of 5 organ dysfunctions (cardiovascular, respiratory, renal, hepatic, coagulation) was assessed using a SOFA score. Each organ has a possible dysfunction score of 0 (no organ dysfunction) to 4 (all organs with dysfunction). Incidence of new organ dysfunction is defined as an increase ≥ 1 from baseline to post baseline up until the end of the period (e.g. going from 1-2) in any of the individual SOFA scores. Incidence of new organ failures is defined as a change in any of the individual SOFA scores from (0-2) at baseline to (3-4) post baseline up until the end of the period (Day 7 or 30) (if the SOFA scores goes from (0-2) to (3-4) and back to (0-2) again within the period, that will still count as a new organ failure). Percentage of subjects with new organ dysfunction and new organ failure (based on the SOFA Score) up to Day 7 and Day 30 are reported.
Time frame: Up to Day 7 and Day 30
Population: The FAS comprised of all subjects who were enrolled (i.e. randomized \[as planned\]) and dosed. The primary comparison to determine statistical and clinical significance was between all subjects in all selepressin arms (pooled together and treated as a single arm) and all subjects in the placebo arm, to control Type 1 error.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Subjects With New Organ Dysfunction and New Organ Failure (Based on the SOFA Score) up to Day 7 and Day 30 | New organ failure (Day 7) | 44.18 percentage of subjects |
| Placebo | Percentage of Subjects With New Organ Dysfunction and New Organ Failure (Based on the SOFA Score) up to Day 7 and Day 30 | New organ dysfunction (Day 7) | 76.41 percentage of subjects |
| Placebo | Percentage of Subjects With New Organ Dysfunction and New Organ Failure (Based on the SOFA Score) up to Day 7 and Day 30 | New organ failure (Day 30) | 56.91 percentage of subjects |
| Placebo | Percentage of Subjects With New Organ Dysfunction and New Organ Failure (Based on the SOFA Score) up to Day 7 and Day 30 | New organ dysfunction (Day 30) | 80.44 percentage of subjects |
| Selepressin Pooled | Percentage of Subjects With New Organ Dysfunction and New Organ Failure (Based on the SOFA Score) up to Day 7 and Day 30 | New organ failure (Day 30) | 57.15 percentage of subjects |
| Selepressin Pooled | Percentage of Subjects With New Organ Dysfunction and New Organ Failure (Based on the SOFA Score) up to Day 7 and Day 30 | New organ dysfunction (Day 30) | 84.08 percentage of subjects |
| Selepressin Pooled | Percentage of Subjects With New Organ Dysfunction and New Organ Failure (Based on the SOFA Score) up to Day 7 and Day 30 | New organ failure (Day 7) | 47.39 percentage of subjects |
| Selepressin Pooled | Percentage of Subjects With New Organ Dysfunction and New Organ Failure (Based on the SOFA Score) up to Day 7 and Day 30 | New organ dysfunction (Day 7) | 81.95 percentage of subjects |
Comparison: Percentage of subjects with new organ dysfunction up to Day 7p-value: 0.06395% CI: [0.98, 2]Regression, Logistic
Comparison: Percentage of subjects with new organ dysfunction up to Day 30p-value: 0.187595% CI: [0.89, 1.86]Regression, Logistic
Comparison: Percentage of subjects with new organ failure up to Day 7p-value: 0.438295% CI: [0.82, 1.58]Regression, Logistic
Comparison: Percentage of subjects with new organ failure up to Day 30p-value: 0.952995% CI: [0.73, 1.39]Regression, Logistic
Secondary
Renal Replacement Therapy (RRT)-Free Days
RRT-free days was defined as the number of days a subject is free of treatment with any form of RRT (continuous RRT, intermittent hemodialysis or peritoneal dialysis) and the intermittent periods were not included. RRT-free days was analyzed excluding subjects on RRT for chronic renal failure at time of randomization.
Time frame: Up to Day 30
Population: The FAS comprised of all subjects who were enrolled (i.e. randomized \[as planned\]) and dosed. The primary comparison to determine statistical and clinical significance was between all subjects in all selepressin arms (pooled together and treated as a single arm) and all subjects in the placebo arm, to control Type 1 error.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Renal Replacement Therapy (RRT)-Free Days | 18.21 days |
| Selepressin Pooled | Renal Replacement Therapy (RRT)-Free Days | 18.50 days |
Comparison: This endpoint was analyzed using a van Elteren test. The analysis was a test of superiority using a two-sided 5% significance level.p-value: 0.845895% CI: [-2.07, 2.65]van Elteren test
Secondary
The Percentage of Subjects With RRT up to Day 30 (Counting Subjects Who Died as on RRT and Excluding Subjects on RRT for Chronic Renal Failure at the Time of Randomization)
Renal replacement therapy is defined as continuous RRT, intermittent hemodialysis, or peritoneal dialysis. In order to ensure that any reduction in the incidence of RRT was not caused by an increase in mortality, all subjects dying within the 30-day period were counted as on RRT.
Time frame: Up to Day 30
Population: The FAS comprised of all subjects who were enrolled (i.e. randomized \[as planned\]) and dosed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | The Percentage of Subjects With RRT up to Day 30 (Counting Subjects Who Died as on RRT and Excluding Subjects on RRT for Chronic Renal Failure at the Time of Randomization) | No | 135 Participants |
| Placebo | The Percentage of Subjects With RRT up to Day 30 (Counting Subjects Who Died as on RRT and Excluding Subjects on RRT for Chronic Renal Failure at the Time of Randomization) | Yes | 126 Participants |
| Selepressin Pooled | The Percentage of Subjects With RRT up to Day 30 (Counting Subjects Who Died as on RRT and Excluding Subjects on RRT for Chronic Renal Failure at the Time of Randomization) | Yes | 85 Participants |
| Selepressin Pooled | The Percentage of Subjects With RRT up to Day 30 (Counting Subjects Who Died as on RRT and Excluding Subjects on RRT for Chronic Renal Failure at the Time of Randomization) | No | 102 Participants |
| Selepressin 3.75 ng/kg/Min | The Percentage of Subjects With RRT up to Day 30 (Counting Subjects Who Died as on RRT and Excluding Subjects on RRT for Chronic Renal Failure at the Time of Randomization) | Yes | 85 Participants |
| Selepressin 3.75 ng/kg/Min | The Percentage of Subjects With RRT up to Day 30 (Counting Subjects Who Died as on RRT and Excluding Subjects on RRT for Chronic Renal Failure at the Time of Randomization) | No | 89 Participants |
| Selepressin 5.25 ng/kg/Min | The Percentage of Subjects With RRT up to Day 30 (Counting Subjects Who Died as on RRT and Excluding Subjects on RRT for Chronic Renal Failure at the Time of Randomization) | No | 100 Participants |
| Selepressin 5.25 ng/kg/Min | The Percentage of Subjects With RRT up to Day 30 (Counting Subjects Who Died as on RRT and Excluding Subjects on RRT for Chronic Renal Failure at the Time of Randomization) | Yes | 89 Participants |
| Selepressin Pooled | The Percentage of Subjects With RRT up to Day 30 (Counting Subjects Who Died as on RRT and Excluding Subjects on RRT for Chronic Renal Failure at the Time of Randomization) | Yes | 259 Participants |
| Selepressin Pooled | The Percentage of Subjects With RRT up to Day 30 (Counting Subjects Who Died as on RRT and Excluding Subjects on RRT for Chronic Renal Failure at the Time of Randomization) | No | 291 Participants |
Secondary
Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180
The EuroQoL-5-Dimensions (EQ-5D™) was used to assess the overall health of each subject. EQ-5D™ is a standardised instrument for use as a measure of health outcome. The first part of the instrument includes 5 dimensions where the subject indicates which of the given statements best describes the health state on the day of questionnaire completion. The second part contains a visual analogue scale (VAS) where the subject indicates how good or bad his or her own health is on the day of questionnaire completion. EQ-5D-5L will be analyzed by the index value (Range: 0-1; 0=dead state, 1=full health state), the overall quality-adjusted life year (QALY), and the VAS score (Range: 0-100; 0=worst health state, 100=best health state). The EQ-5D-5L was completed at baseline and at the scheduled follow-up days (i.e. Day 30, Day 60, Day 90, and Day 180). Data for EQ VAS score and EQ-5D-5L index score are reported in this endpoint.
Time frame: Baseline and Days 30, 60, 90 and 180
Population: The FAS comprised of all subjects who were enrolled (i.e. randomized \[as planned\]) and dosed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L index score (Day 30) | 0.5706 score on a scale | Standard Deviation 0.29463 |
| Placebo | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ VAS score (Day 90) | 68.2 score on a scale | Standard Deviation 19.61 |
| Placebo | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L index score (Baseline) | 0.7305 score on a scale | Standard Deviation 0.25098 |
| Placebo | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ VAS score (Baseline) | 69.2 score on a scale | Standard Deviation 21.13 |
| Placebo | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L index score (Day 60) | 0.6707 score on a scale | Standard Deviation 0.2616 |
| Placebo | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ VAS score (Day 180) | 72.6 score on a scale | Standard Deviation 20.07 |
| Placebo | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ VAS score (Day 60) | 64.5 score on a scale | Standard Deviation 20.58 |
| Placebo | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L index score (Day 180) | 0.7627 score on a scale | Standard Deviation 0.2217 |
| Placebo | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ VAS score (Day 30) | 59.4 score on a scale | Standard Deviation 21.21 |
| Placebo | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L index score (Day 90) | 0.7207 score on a scale | Standard Deviation 0.22523 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L index score (Baseline) | 0.7648 score on a scale | Standard Deviation 0.22393 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L index score (Day 30) | 0.5600 score on a scale | Standard Deviation 0.27848 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ VAS score (Day 30) | 54.7 score on a scale | Standard Deviation 21.12 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ VAS score (Day 180) | 71.2 score on a scale | Standard Deviation 18.55 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ VAS score (Day 60) | 62.6 score on a scale | Standard Deviation 20.92 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ VAS score (Day 90) | 65.9 score on a scale | Standard Deviation 20.7 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ VAS score (Baseline) | 69.9 score on a scale | Standard Deviation 21.69 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L index score (Day 180) | 0.7572 score on a scale | Standard Deviation 0.19803 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L index score (Day 60) | 0.6788 score on a scale | Standard Deviation 0.22544 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L index score (Day 90) | 0.7018 score on a scale | Standard Deviation 0.26544 |
| Selepressin 3.75 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ VAS score (Day 30) | 53.8 score on a scale | Standard Deviation 19.63 |
| Selepressin 3.75 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ VAS score (Baseline) | 67.0 score on a scale | Standard Deviation 21.6 |
| Selepressin 3.75 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ VAS score (Day 90) | 67.0 score on a scale | Standard Deviation 17.5 |
| Selepressin 3.75 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ VAS score (Day 180) | 67.4 score on a scale | Standard Deviation 21.39 |
| Selepressin 3.75 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L index score (Day 30) | 0.5089 score on a scale | Standard Deviation 0.29004 |
| Selepressin 3.75 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L index score (Day 60) | 0.6719 score on a scale | Standard Deviation 0.21777 |
| Selepressin 3.75 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L index score (Day 180) | 0.7409 score on a scale | Standard Deviation 0.19813 |
| Selepressin 3.75 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ VAS score (Day 60) | 62.6 score on a scale | Standard Deviation 18.94 |
| Selepressin 3.75 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L index score (Baseline) | 0.7576 score on a scale | Standard Deviation 0.2307 |
| Selepressin 3.75 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L index score (Day 90) | 0.7290 score on a scale | Standard Deviation 0.21608 |
| Selepressin 5.25 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L index score (Baseline) | 0.7380 score on a scale | Standard Deviation 0.22152 |
| Selepressin 5.25 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ VAS score (Day 180) | 69.7 score on a scale | Standard Deviation 20.29 |
| Selepressin 5.25 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ VAS score (Day 90) | 68.1 score on a scale | Standard Deviation 18.63 |
| Selepressin 5.25 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L index score (Day 90) | 0.6810 score on a scale | Standard Deviation 0.2496 |
| Selepressin 5.25 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ VAS score (Day 60) | 63.8 score on a scale | Standard Deviation 20.3 |
| Selepressin 5.25 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ VAS score (Day 30) | 53.9 score on a scale | Standard Deviation 23.99 |
| Selepressin 5.25 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L index score (Day 180) | 0.7435 score on a scale | Standard Deviation 0.23729 |
| Selepressin 5.25 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ VAS score (Baseline) | 67.4 score on a scale | Standard Deviation 22.83 |
| Selepressin 5.25 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L index score (Day 30) | 0.5283 score on a scale | Standard Deviation 0.3358 |
| Selepressin 5.25 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L index score (Day 60) | 0.6746 score on a scale | Standard Deviation 0.25391 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L index score (Baseline) | 0.7525 score on a scale | Standard Deviation 0.22481 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ VAS score (Day 180) | 69.5 score on a scale | Standard Deviation 20.08 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L index score (Day 90) | 0.7032 score on a scale | Standard Deviation 0.24515 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ VAS score (Day 30) | 54.2 score on a scale | Standard Deviation 21.65 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ VAS score (Day 90) | 67.0 score on a scale | Standard Deviation 18.98 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L index score (Day 180) | 0.7472 score on a scale | Standard Deviation 0.21112 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ VAS score (Baseline) | 68.1 score on a scale | Standard Deviation 22.07 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L index score (Day 60) | 0.6753 score on a scale | Standard Deviation 0.23222 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L index score (Day 30) | 0.5335 score on a scale | Standard Deviation 0.30245 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ VAS score (Day 60) | 63.0 score on a scale | Standard Deviation 20.04 |
Secondary
Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180
The EQ-5D™ was used to assess the overall health of each subject. EQ-5D™ is a standardised instrument for use as a measure of health outcome. The first part of the instrument includes 5 dimensions where the subject indicates which of the given statements best describes the health state on the day of questionnaire completion. The second part contains a VAS where the subject indicates how good or bad his or her own health is on the day of questionnaire completion. EQ-5D-5L will be analyzed by the index value (Range: 0-1; 0=dead state, 1=full health state), the overall QALY, and the VAS score (Range: 0-100; 0=worst health state, 100=best health state). The EQ-5D-5L was completed at baseline and at the scheduled follow-up days (i.e. Day 30, Day 60, Day 90, and Day 180). Data for EQ-5D-5L QALY is reported in this endpoint.
Time frame: Days 30, 60, 90 and 180
Population: The FAS comprised of all subjects who were enrolled (i.e. randomized \[as planned\]) and dosed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L QALY (Day 60) | 0.088 Quality-adjusted life-year | Standard Deviation 0.0683 |
| Placebo | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L QALY (Day 30) | 0.036 Quality-adjusted life-year | Standard Deviation 0.0558 |
| Placebo | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L QALY (Day 90) | 0.144 Quality-adjusted life-year | Standard Deviation 0.0819 |
| Placebo | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L QALY (Day 180) | 0.330 Quality-adjusted life-year | Standard Deviation 0.1174 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L QALY (Day 30) | 0.039 Quality-adjusted life-year | Standard Deviation 0.0448 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L QALY (Day 90) | 0.146 Quality-adjusted life-year | Standard Deviation 0.0725 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L QALY (Day 180) | 0.338 Quality-adjusted life-year | Standard Deviation 0.1239 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L QALY (Day 60) | 0.093 Quality-adjusted life-year | Standard Deviation 0.0588 |
| Selepressin 3.75 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L QALY (Day 30) | 0.033 Quality-adjusted life-year | Standard Deviation 0.0388 |
| Selepressin 3.75 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L QALY (Day 60) | 0.085 Quality-adjusted life-year | Standard Deviation 0.0548 |
| Selepressin 3.75 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L QALY (Day 90) | 0.145 Quality-adjusted life-year | Standard Deviation 0.067 |
| Selepressin 3.75 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L QALY (Day 180) | 0.329 Quality-adjusted life-year | Standard Deviation 0.1011 |
| Selepressin 5.25 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L QALY (Day 30) | 0.030 Quality-adjusted life-year | Standard Deviation 0.0501 |
| Selepressin 5.25 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L QALY (Day 60) | 0.084 Quality-adjusted life-year | Standard Deviation 0.0643 |
| Selepressin 5.25 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L QALY (Day 90) | 0.139 Quality-adjusted life-year | Standard Deviation 0.076 |
| Selepressin 5.25 ng/kg/Min | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L QALY (Day 180) | 0.319 Quality-adjusted life-year | Standard Deviation 0.1155 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L QALY (Day 30) | 0.034 Quality-adjusted life-year | Standard Deviation 0.0451 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L QALY (Day 60) | 0.087 Quality-adjusted life-year | Standard Deviation 0.0595 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L QALY (Day 180) | 0.328 Quality-adjusted life-year | Standard Deviation 0.1137 |
| Selepressin Pooled | Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180 | EQ-5D-5L QALY (Day 90) | 0.143 Quality-adjusted life-year | Standard Deviation 0.0718 |
Secondary
Vasopressor-free Days up to Day 30
Number of days from start of treatment to 30 days thereafter during which the subject is free of treatment with vasopressors, i.e. less than 60 min during any contiguous 24-h period.
Time frame: Up to Day 30
Population: The FAS comprised of all subjects who were enrolled (i.e. randomized \[as planned\]) and dosed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Vasopressor-free Days up to Day 30 | 25.30 days |
| Selepressin Pooled | Vasopressor-free Days up to Day 30 | 25.60 days |
| Selepressin 3.75 ng/kg/Min | Vasopressor-free Days up to Day 30 | 23.30 days |
| Selepressin 5.25 ng/kg/Min | Vasopressor-free Days up to Day 30 | 25.30 days |
| Selepressin Pooled | Vasopressor-free Days up to Day 30 | 25.10 days |