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Selepressin Evaluation Programme for Sepsis-Induced Shock - Adaptive Clinical Trial (SEPSIS-ACT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02508649
Recruitment Status : Terminated (Terminated due to futility)
First Posted : July 27, 2015
Results First Posted : April 6, 2021
Last Update Posted : April 6, 2021
Sponsor:
Information provided by (Responsible Party):
Ferring Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Septic Shock
Interventions Drug: selepressin
Drug: placebo
Enrollment 868
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.

Arm/Group Title Placebo Selepressin 2.5 ng/kg/Min Selepressin 3.75 ng/kg/Min Selepressin 5.25 ng/kg/Min
Hide Arm/Group Description Sterile 0.9% sodium chloride solution given as an infusion, was used as the placebo. Starting dose: 1.7 ng/kg/min selepressin; Maximum dose: 2.5 ng/kg/min selepressin, given as an infusion. Starting dose: 2.5 ng/kg/min selepressin; Maximum dose: 3.75 ng/kg/min selepressin, given as an infusion. Starting dose: 3.5 ng/kg/min selepressin; Maximum dose: 5.25 ng/kg/min selepressin, given as an infusion.
Period Title: Overall Study
Started 283 197 189 199
Dosed 266 191 177 194
Completed 265 184 174 189
Not Completed 18 13 15 10
Reason Not Completed
Withdrawal by Subject             4             6             5             6
Investigator withdrew the subject             1             2             1             0
Post randomization screening failure             12             4             9             3
Lost to Follow-up             1             1             0             1
Arm/Group Title Placebo Selepressin 2.5 ng/kg/Min Selepressin 3.75 ng/kg/Min Selepressin 5.25 ng/kg/Min Total
Hide Arm/Group Description Sterile 0.9% sodium chloride solution given as an infusion, was used as the placebo. Starting dose: 1.7 ng/kg/min selepressin; Maximum dose: 2.5 ng/kg/min selepressin, given as an infusion. Starting dose: 2.5 ng/kg/min selepressin; Maximum dose: 3.75 ng/kg/min selepressin, given as an infusion. Starting dose: 3.5 ng/kg/min selepressin; Maximum dose: 5.25 ng/kg/min selepressin, given as an infusion. Total of all reporting groups
Overall Number of Baseline Participants 266 191 177 194 828
Hide Baseline Analysis Population Description
The full analysis set (FAS) comprised of all the subjects who were enrolled (i.e. randomized [as planned]) and dosed.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 266 participants 191 participants 177 participants 194 participants 828 participants
65.7  (14.56) 66.0  (12.76) 67.2  (13.13) 66.8  (12.47) 66.3  (13.37)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 266 participants 191 participants 177 participants 194 participants 828 participants
Female
121
  45.5%
80
  41.9%
70
  39.5%
70
  36.1%
341
  41.2%
Male
145
  54.5%
111
  58.1%
107
  60.5%
124
  63.9%
487
  58.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 266 participants 191 participants 177 participants 194 participants 828 participants
Hispanic or Latino
4
   1.5%
3
   1.6%
1
   0.6%
4
   2.1%
12
   1.4%
Not Hispanic or Latino
262
  98.5%
188
  98.4%
176
  99.4%
190
  97.9%
816
  98.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 266 participants 191 participants 177 participants 194 participants 828 participants
American Indian or Alaska Native
1
   0.4%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.1%
Asian
1
   0.4%
2
   1.0%
5
   2.8%
4
   2.1%
12
   1.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
4
   1.5%
3
   1.6%
11
   6.2%
7
   3.6%
25
   3.0%
White
260
  97.7%
186
  97.4%
161
  91.0%
183
  94.3%
790
  95.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Baseline BMI   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 265 participants 191 participants 176 participants 192 participants 824 participants
27.47  (7.234) 27.56  (8.778) 28.04  (7.885) 27.98  (8.565) 27.73  (8.055)
[1]
Measure Analysis Population Description: Number analyzed differs from the overall population as baseline body mass index (BMI) was not calculated for some of the subjects. The reason is that data was not collected for all subjects.
1.Primary Outcome
Title Vasopressor- and Mechanical Ventilator-free Days (PVFDs)
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Placebo Selepressin Pooled
Hide Arm/Group Description:
Sterile 0.9% sodium chloride solution given as an infusion, was used as the placebo.
All selepressin arms pooled together and treated as a single arm.
Overall Number of Participants Analyzed 266 562
Least Squares Mean (95% Confidence Interval)
Unit of Measure: days
14.45
(12.82 to 16.09)
15.00
(13.77 to 16.23)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Selepressin Pooled
Comments The primary endpoint was analyzed using a van Elteren test. The analysis included a test of superiority using a two-sided 5% significance level.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3015
Comments [Not Specified]
Method van Elteren test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.55
Confidence Interval (2-Sided) 95%
-1.34 to 2.43
Estimation Comments [Not Specified]
2.Secondary Outcome
Title All-cause Mortality
Hide Description All-cause mortality defined as the percentage of subjects that have died, regardless of cause.
Time Frame At Day 90
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Placebo Selepressin Pooled
Hide Arm/Group Description:
Sterile 0.9% sodium chloride solution given as an infusion, was used as the placebo.
All selepressin arms pooled together and treated as a single arm.
Overall Number of Participants Analyzed 257 526
Measure Type: Number
Unit of Measure: percentage of subjects
39.44 40.59
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Selepressin Pooled
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7694
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.049
Confidence Interval (2-Sided) 95%
0.762 to 1.445
Estimation Comments An odds ratio < 1 in proportion of subjects dying indicates lower mortality in the selepressin group.
3.Secondary Outcome
Title Renal Replacement Therapy (RRT)-Free Days
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Placebo Selepressin Pooled
Hide Arm/Group Description:
Sterile 0.9% sodium chloride solution given as an infusion, was used as the placebo.
All selepressin arms pooled together and treated as a single arm.
Overall Number of Participants Analyzed 261 550
Least Squares Mean (95% Confidence Interval)
Unit of Measure: days
18.21
(16.14 to 20.29)
18.50
(17.03 to 19.98)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Selepressin Pooled
Comments This endpoint was analyzed using a van Elteren test. The analysis was a test of superiority using a two-sided 5% significance level.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8458
Comments [Not Specified]
Method van Elteren test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.29
Confidence Interval (2-Sided) 95%
-2.07 to 2.65
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Intensive Care Unit (ICU)-Free Days
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Placebo Selepressin Pooled
Hide Arm/Group Description:
Sterile 0.9% sodium chloride solution given as an infusion, was used as the placebo.
All selepressin arms pooled together and treated as a single arm.
Overall Number of Participants Analyzed 266 562
Least Squares Mean (95% Confidence Interval)
Unit of Measure: days
12.15
(10.66 to 13.64)
12.64
(11.51 to 13.76)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Selepressin Pooled
Comments This endpoint was analyzed using a van Elteren test. The analysis was a test of superiority using a two-sided 5% significance level.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4124
Comments [Not Specified]
Method van Elteren test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.49
Confidence Interval (2-Sided) 95%
-1.22 to 2.19
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Vasopressor-free Days up to Day 30
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed.
Arm/Group Title Placebo Selepressin 2.5 ng/kg/Min Selepressin 3.75 ng/kg/Min Selepressin 5.25 ng/kg/Min Selepressin Pooled
Hide Arm/Group Description:
Sterile 0.9% sodium chloride solution given as an infusion, was used as the placebo.
Starting dose: 1.7 ng/kg/min selepressin; Maximum dose: 2.5 ng/kg/min selepressin, given as an infusion.
Starting dose: 2.5 ng/kg/min selepressin; Maximum dose: 3.75 ng/kg/min selepressin, given as an infusion.
Starting dose: 3.5 ng/kg/min selepressin; Maximum dose: 5.25 ng/kg/min selepressin, given as an infusion.
All selepressin arms pooled together and treated as a single arm.
Overall Number of Participants Analyzed 266 191 177 194 562
Median (Inter-Quartile Range)
Unit of Measure: days
25.30
(0.00 to 28.30)
25.60
(0.00 to 28.60)
23.30
(0.00 to 28.60)
25.30
(0.00 to 28.80)
25.10
(0.00 to 28.70)
6.Secondary Outcome
Title Mechanical Ventilator-free Days up to Day 30
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed.
Arm/Group Title Placebo Selepressin 2.5 ng/kg/Min Selepressin 3.75 ng/kg/Min Selepressin 5.25 ng/kg/Min Selepressin Pooled
Hide Arm/Group Description:
Sterile 0.9% sodium chloride solution given as an infusion, was used as the placebo.
Starting dose: 1.7 ng/kg/min selepressin; Maximum dose: 2.5 ng/kg/min selepressin, given as an infusion.
Starting dose: 2.5 ng/kg/min selepressin; Maximum dose: 3.75 ng/kg/min selepressin, given as an infusion.
Starting dose: 3.5 ng/kg/min selepressin; Maximum dose: 5.25 ng/kg/min selepressin, given as an infusion.
All selepressin arms pooled together and treated as a single arm.
Overall Number of Participants Analyzed 266 191 177 194 562
Median (Inter-Quartile Range)
Unit of Measure: days
19.80
(0.00 to 29.40)
18.90
(0.00 to 30.00)
17.20
(0.00 to 29.10)
17.50
(0.00 to 29.50)
17.50
(0.00 to 29.80)
7.Secondary Outcome
Title Duration of Septic Shock (i.e. Vasopressor Use) up to Day 30
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed.
Arm/Group Title Placebo Selepressin 2.5 ng/kg/Min Selepressin 3.75 ng/kg/Min Selepressin 5.25 ng/kg/Min Selepressin Pooled
Hide Arm/Group Description:
Sterile 0.9% sodium chloride solution given as an infusion, was used as the placebo.
Starting dose: 1.7 ng/kg/min selepressin; Maximum dose: 2.5 ng/kg/min selepressin, given as an infusion.
Starting dose: 2.5 ng/kg/min selepressin; Maximum dose: 3.75 ng/kg/min selepressin, given as an infusion.
Starting dose: 3.5 ng/kg/min selepressin; Maximum dose: 5.25 ng/kg/min selepressin, given as an infusion.
All selepressin arms pooled together and treated as a single arm.
Overall Number of Participants Analyzed 266 191 177 194 562
Median (Inter-Quartile Range)
Unit of Measure: days
2.220
(1.110 to 4.420)
1.660
(0.800 to 2.990)
1.790
(0.810 to 4.370)
1.465
(0.750 to 3.530)
1.635
(0.770 to 3.650)
8.Secondary Outcome
Title Duration of Mechanical Ventilation up to Day 30
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed.
Arm/Group Title Placebo Selepressin 2.5 ng/kg/Min Selepressin 3.75 ng/kg/Min Selepressin 5.25 ng/kg/Min Selepressin Pooled
Hide Arm/Group Description:
Sterile 0.9% sodium chloride solution given as an infusion, was used as the placebo.
Starting dose: 1.7 ng/kg/min selepressin; Maximum dose: 2.5 ng/kg/min selepressin, given as an infusion.
Starting dose: 2.5 ng/kg/min selepressin; Maximum dose: 3.75 ng/kg/min selepressin, given as an infusion.
Starting dose: 3.5 ng/kg/min selepressin; Maximum dose: 5.25 ng/kg/min selepressin, given as an infusion.
All selepressin arms pooled together and treated as a single arm.
Overall Number of Participants Analyzed 266 191 177 194 562
Median (Inter-Quartile Range)
Unit of Measure: days
2.255
(0.000 to 8.710)
1.690
(0.000 to 8.250)
2.800
(0.100 to 8.880)
1.910
(0.000 to 7.680)
1.990
(0.000 to 8.250)
9.Secondary Outcome
Title 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)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed.
Arm/Group Title Placebo Selepressin 2.5 ng/kg/Min Selepressin 3.75 ng/kg/Min Selepressin 5.25 ng/kg/Min Selepressin Pooled
Hide Arm/Group Description:
Sterile 0.9% sodium chloride solution given as an infusion, was used as the placebo.
Starting dose: 1.7 ng/kg/min selepressin; Maximum dose: 2.5 ng/kg/min selepressin, given as an infusion.
Starting dose: 2.5 ng/kg/min selepressin; Maximum dose: 3.75 ng/kg/min selepressin, given as an infusion.
Starting dose: 3.5 ng/kg/min selepressin; Maximum dose: 5.25 ng/kg/min selepressin, given as an infusion.
All selepressin arms pooled together and treated as a single arm.
Overall Number of Participants Analyzed 261 187 174 189 550
Measure Type: Count of Participants
Unit of Measure: Participants
No
135
  51.7%
102
  54.5%
89
  51.1%
100
  52.9%
291
  52.9%
Yes
126
  48.3%
85
  45.5%
85
  48.9%
89
  47.1%
259
  47.1%
10.Secondary Outcome
Title Duration of RRT up to Day 90 (Excluding Subjects on RRT for Chronic Failure at the Time of Randomization)
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed.
Arm/Group Title Placebo Selepressin 2.5 ng/kg/Min Selepressin 3.75 ng/kg/Min Selepressin 5.25 ng/kg/Min Selepressin Pooled
Hide Arm/Group Description:
Sterile 0.9% sodium chloride solution given as an infusion, was used as the placebo.
Starting dose: 1.7 ng/kg/min selepressin; Maximum dose: 2.5 ng/kg/min selepressin, given as an infusion.
Starting dose: 2.5 ng/kg/min selepressin; Maximum dose: 3.75 ng/kg/min selepressin, given as an infusion.
Starting dose: 3.5 ng/kg/min selepressin; Maximum dose: 5.25 ng/kg/min selepressin, given as an infusion.
All selepressin arms pooled together and treated as a single arm.
Overall Number of Participants Analyzed 261 187 174 189 550
Mean (Standard Deviation)
Unit of Measure: days
1.634  (5.5380) 1.739  (5.5593) 1.876  (6.0300) 2.459  (10.1365) 2.030  (7.5640)
11.Secondary Outcome
Title 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
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Placebo Selepressin Pooled
Hide Arm/Group Description:
Sterile 0.9% sodium chloride solution given as an infusion, was used as the placebo.
All selepressin arms pooled together and treated as a single arm.
Overall Number of Participants Analyzed 263 555
Least Squares Mean (95% Confidence Interval)
Unit of Measure: score on a scale
Overall score (Day 1) Number Analyzed 247 participants 515 participants
9.95
(9.31 to 10.60)
9.44
(9.00 to 9.89)
Overall score (Day 3) Number Analyzed 240 participants 474 participants
8.95
(8.30 to 9.59)
9.06
(8.60 to 9.51)
Overall score (Day 7) Number Analyzed 182 participants 382 participants
8.08
(7.41 to 8.76)
8.63
(8.17 to 9.10)
Individual (Respiratory) score Day 1 Number Analyzed 256 participants 532 participants
2.58
(2.45 to 2.71)
2.50
(2.41 to 2.59)
Individual (Respiratory) score Day 3 Number Analyzed 245 participants 483 participants
2.43
(2.30 to 2.56)
2.40
(2.31 to 2.49)
Individual (Respiratory) score Day 7 Number Analyzed 186 participants 388 participants
2.38
(2.24 to 2.52)
2.41
(2.31 to 2.50)
Individual (Cardiovascular) score Day 1 Number Analyzed 263 participants 555 participants
3.66
(3.47 to 3.85)
3.23
(3.10 to 3.36)
Individual (Cardiovascular) score Day 3 Number Analyzed 250 participants 496 participants
2.33
(2.14 to 2.53)
2.08
(1.95 to 2.22)
Individual (Cardiovascular) score Day 7 Number Analyzed 188 participants 396 participants
1.79
(1.58 to 1.99)
1.65
(1.51 to 1.79)
Individual (Renal) score Day 1 Number Analyzed 263 participants 555 participants
1.64
(1.47 to 1.81)
1.59
(1.48 to 1.71)
Individual (Renal) score Day 3 Number Analyzed 250 participants 496 participants
1.52
(1.35 to 1.69)
1.61
(1.49 to 1.73)
Individual (Renal) score Day 7 Number Analyzed 188 participants 396 participants
1.46
(1.28 to 1.64)
1.63
(1.50 to 1.75)
Individual (Coagulation) score Day 1 Number Analyzed 260 participants 551 participants
1.15
(1.00 to 1.30)
1.27
(1.16 to 1.37)
Individual (Coagulation) score Day 3 Number Analyzed 248 participants 495 participants
1.50
(1.35 to 1.66)
1.73
(1.62 to 1.84)
Individual (Coagulation) score Day 7 Number Analyzed 187 participants 395 participants
1.30
(1.14 to 1.46)
1.53
(1.42 to 1.64)
Individual (Liver) score Day 1 Number Analyzed 256 participants 540 participants
0.87
(0.71 to 1.03)
0.72
(0.61 to 0.83)
Individual (Liver) score Day 3 Number Analyzed 247 participants 488 participants
1.11
(0.95 to 1.28)
1.07
(0.95 to 1.18)
Individual (Liver) score Day 7 Number Analyzed 185 participants 391 participants
1.17
(1.00 to 1.35)
1.35
(1.23 to 1.46)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Selepressin Pooled
Comments Overall score using a modified version of the SOFA on Day 1
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2009
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.51
Confidence Interval (2-Sided) 95%
-1.30 to 0.27
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Selepressin Pooled
Comments Overall score using a modified version of the SOFA on Day 3
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7894
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.11
Confidence Interval (2-Sided) 95%
-0.68 to 0.90
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Selepressin Pooled
Comments Overall score using a modified version of the SOFA on Day 7
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1888
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.55
Confidence Interval (2-Sided) 95%
-0.27 to 1.37
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Selepressin Pooled
Comments Individual organ (respiratory) score using a modified version of the SOFA on Day 1
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2997
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.08
Confidence Interval (2-Sided) 95%
-0.24 to 0.07
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Selepressin Pooled
Comments Individual organ (respiratory) score using a modified version of the SOFA on Day 3
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6796
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-0.19 to 0.12
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Selepressin Pooled
Comments Individual organ (respiratory) score using a modified version of the SOFA on Day 7
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7467
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
-0.14 to 0.19
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, Selepressin Pooled
Comments Individual organ (cardiovascular) score using a modified version of the SOFA on Day 1
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.42
Confidence Interval (2-Sided) 95%
-0.65 to -0.19
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, Selepressin Pooled
Comments Individual organ (cardiovascular) score using a modified version of the SOFA on Day 3
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0349
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.25
Confidence Interval (2-Sided) 95%
-0.49 to -0.02
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, Selepressin Pooled
Comments Individual organ (cardiovascular) score using a modified version of the SOFA on Day 7
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2787
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.14
Confidence Interval (2-Sided) 95%
-0.39 to 0.11
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, Selepressin Pooled
Comments Individual organ (renal) score using a modified version of the SOFA on Day 1
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6476
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.05
Confidence Interval (2-Sided) 95%
-0.26 to 0.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, Selepressin Pooled
Comments Individual organ (renal) score using a modified version of the SOFA on Day 3
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4313
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
-0.13 to 0.29
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, Selepressin Pooled
Comments Individual organ (renal) score using a modified version of the SOFA on Day 7
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1334
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.17
Confidence Interval (2-Sided) 95%
-0.05 to 0.39
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Placebo, Selepressin Pooled
Comments Individual organ (coagulation) score using a modified version of the SOFA on Day 1
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2126
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.12
Confidence Interval (2-Sided) 95%
-0.07 to 0.30
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Placebo, Selepressin Pooled
Comments Individual organ (coagulation) score using a modified version of the SOFA on Day 3
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0174
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 0.23
Confidence Interval (2-Sided) 95%
0.04 to 0.41
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Placebo, Selepressin Pooled
Comments Individual organ (coagulation) score using a modified version of the SOFA on Day 7
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0194
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.23
Confidence Interval (2-Sided) 95%
0.04 to 0.43
Estimation Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Placebo, Selepressin Pooled
Comments Individual organ (liver) score using a modified version of the SOFA on Day 1
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1284
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-0.35 to 0.04
Estimation Comments [Not Specified]
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Placebo, Selepressin Pooled
Comments Individual organ (liver) score using a modified version of the SOFA on Day 3
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6542
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.05
Confidence Interval (2-Sided) 95%
-0.25 to 0.15
Estimation Comments [Not Specified]
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Placebo, Selepressin Pooled
Comments Individual organ (liver) score using a modified version of the SOFA on Day 7
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1079
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.17
Confidence Interval (2-Sided) 95%
-0.04 to 0.38
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Percentage of Subjects With New Organ Dysfunction and New Organ Failure (Based on the SOFA Score) up to Day 7 and Day 30
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Placebo Selepressin Pooled
Hide Arm/Group Description:
Sterile 0.9% sodium chloride solution given as an infusion, was used as the placebo.
All selepressin arms pooled together and treated as a single arm.
Overall Number of Participants Analyzed 256 536
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of subjects
New organ dysfunction (Day 7)
76.41
(70.42 to 81.51)
81.95
(77.92 to 85.38)
New organ dysfunction (Day 30)
80.44
(74.80 to 85.07)
84.08
(80.21 to 87.31)
New organ failure (Day 7)
44.18
(37.67 to 50.90)
47.39
(42.70 to 52.12)
New organ failure (Day 30)
56.91
(50.23 to 63.35)
57.15
(52.39 to 61.78)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Selepressin Pooled
Comments Percentage of subjects with new organ dysfunction up to Day 7
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0630
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.40
Confidence Interval (2-Sided) 95%
0.98 to 2.00
Estimation Comments Odds ratio is equal to Selepressin pooled/Placebo.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Selepressin Pooled
Comments Percentage of subjects with new organ dysfunction up to Day 30
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1875
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.28
Confidence Interval (2-Sided) 95%
0.89 to 1.86
Estimation Comments Odds ratio is equal to Selepressin pooled/Placebo.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Selepressin Pooled
Comments Percentage of subjects with new organ failure up to Day 7
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4382
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.14
Confidence Interval (2-Sided) 95%
0.82 to 1.58
Estimation Comments Odds ratio is equal to Selepressin pooled/Placebo.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Selepressin Pooled
Comments Percentage of subjects with new organ failure up to Day 30
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9529
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.73 to 1.39
Estimation Comments Odds ratio is equal to Selepressin pooled/Placebo.
13.Secondary Outcome
Title ICU Length of Stay up to Day 30
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed.
Arm/Group Title Placebo Selepressin 2.5 ng/kg/Min Selepressin 3.75 ng/kg/Min Selepressin 5.25 ng/kg/Min Selepressin Pooled
Hide Arm/Group Description:
Sterile 0.9% sodium chloride solution given as an infusion, was used as the placebo.
Starting dose: 1.7 ng/kg/min selepressin; Maximum dose: 2.5 ng/kg/min selepressin, given as an infusion.
Starting dose: 2.5 ng/kg/min selepressin; Maximum dose: 3.75 ng/kg/min selepressin, given as an infusion.
Starting dose: 3.5 ng/kg/min selepressin; Maximum dose: 5.25 ng/kg/min selepressin, given as an infusion.
All selepressin arms pooled together and treated as a single arm.
Overall Number of Participants Analyzed 266 191 177 194 562
Median (Inter-Quartile Range)
Unit of Measure: days
6.755
(3.110 to 16.110)
4.940
(2.500 to 13.530)
6.460
(2.880 to 15.530)
5.960
(2.790 to 14.380)
5.695
(2.710 to 14.430)
14.Secondary Outcome
Title All-cause Mortality (Defined as the Percentage of Subjects That Have Died, Regardless of Cause) at Day 30 and Day 180
Hide Description All-cause mortality defined as the percentage of subjects that have died, regardless of cause.
Time Frame At Day 30 and Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed.
Arm/Group Title Placebo Selepressin 2.5 ng/kg/Min Selepressin 3.75 ng/kg/Min Selepressin 5.25 ng/kg/Min Selepressin Pooled
Hide Arm/Group Description:
Sterile 0.9% sodium chloride solution given as an infusion, was used as the placebo.
Starting dose: 1.7 ng/kg/min selepressin; Maximum dose: 2.5 ng/kg/min selepressin, given as an infusion.
Starting dose: 2.5 ng/kg/min selepressin; Maximum dose: 3.75 ng/kg/min selepressin, given as an infusion.
Starting dose: 3.5 ng/kg/min selepressin; Maximum dose: 5.25 ng/kg/min selepressin, given as an infusion.
All selepressin arms pooled together and treated as a single arm.
Overall Number of Participants Analyzed 266 191 177 194 562
Measure Type: Count of Participants
Unit of Measure: Participants
Day 30 Number Analyzed 265 participants 187 participants 176 participants 189 participants 552 participants
No
174
  65.7%
121
  64.7%
114
  64.8%
124
  65.6%
359
  65.0%
Yes
91
  34.3%
66
  35.3%
62
  35.2%
65
  34.4%
193
  35.0%
Day 180 Number Analyzed 263 participants 184 participants 172 participants 187 participants 543 participants
No
147
  55.9%
104
  56.5%
96
  55.8%
102
  54.5%
302
  55.6%
Yes
116
  44.1%
80
  43.5%
76
  44.2%
85
  45.5%
241
  44.4%
15.Secondary Outcome
Title Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed.
Arm/Group Title Placebo Selepressin 2.5 ng/kg/Min Selepressin 3.75 ng/kg/Min Selepressin 5.25 ng/kg/Min Selepressin Pooled
Hide Arm/Group Description:
Sterile 0.9% sodium chloride solution given as an infusion, was used as the placebo.
Starting dose: 1.7 ng/kg/min selepressin; Maximum dose: 2.5 ng/kg/min selepressin, given as an infusion.
Starting dose: 2.5 ng/kg/min selepressin; Maximum dose: 3.75 ng/kg/min selepressin, given as an infusion.
Starting dose: 3.5 ng/kg/min selepressin; Maximum dose: 5.25 ng/kg/min selepressin, given as an infusion.
All selepressin arms pooled together and treated as a single arm.
Overall Number of Participants Analyzed 266 191 177 194 562
Mean (Standard Deviation)
Unit of Measure: mL/h
Baseline Number Analyzed 265 participants 187 participants 177 participants 194 participants 558 participants
339.10  (236.53) 342.23  (218.17) 365.14  (255.92) 350.51  (278.28) 352.38  (252.01)
Day 1 Number Analyzed 265 participants 191 participants 177 participants 194 participants 562 participants
104.74  (110.40) 95.14  (116.90) 86.80  (111.86) 66.68  (96.94) 82.68  (109.24)
Day 2 Number Analyzed 241 participants 175 participants 160 participants 181 participants 516 participants
51.78  (79.27) 52.75  (74.12) 48.95  (65.47) 44.35  (73.82) 48.62  (71.39)
Day 3 Number Analyzed 214 participants 148 participants 147 participants 157 participants 452 participants
19.71  (79.94) 24.87  (65.20) 33.34  (67.61) 29.14  (75.19) 29.11  (69.52)
Day 4 Number Analyzed 201 participants 130 participants 130 participants 139 participants 399 participants
2.34  (75.41) 6.76  (59.14) 22.28  (70.95) 19.50  (66.09) 16.25  (65.76)
Day 5 Number Analyzed 173 participants 105 participants 114 participants 124 participants 343 participants
-0.30  (72.84) 1.08  (62.02) 5.94  (71.72) 3.06  (62.49) 3.41  (65.40)
Day 6 Number Analyzed 154 participants 88 participants 92 participants 109 participants 289 participants
-4.70  (61.16) -12.19  (80.30) -3.49  (75.52) -5.91  (64.72) -7.05  (73.03)
Day 7 Number Analyzed 139 participants 84 participants 87 participants 97 participants 268 participants
-5.84  (62.52) -7.36  (63.51) 4.17  (67.38) -12.71  (58.19) -5.55  (63.12)
16.Secondary Outcome
Title Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed.
Arm/Group Title Placebo Selepressin 2.5 ng/kg/Min Selepressin 3.75 ng/kg/Min Selepressin 5.25 ng/kg/Min Selepressin Pooled
Hide Arm/Group Description:
Sterile 0.9% sodium chloride solution given as an infusion, was used as the placebo.
Starting dose: 1.7 ng/kg/min selepressin; Maximum dose: 2.5 ng/kg/min selepressin, given as an infusion.
Starting dose: 2.5 ng/kg/min selepressin; Maximum dose: 3.75 ng/kg/min selepressin, given as an infusion.
Starting dose: 3.5 ng/kg/min selepressin; Maximum dose: 5.25 ng/kg/min selepressin, given as an infusion.
All selepressin arms pooled together and treated as a single arm.
Overall Number of Participants Analyzed 266 191 177 194 562
Mean (Standard Deviation)
Unit of Measure: mL
Baseline Number Analyzed 265 participants 187 participants 177 participants 194 participants 558 participants
3715.19  (2191.23) 4043.77  (2650.73) 4250.88  (2943.81) 3874.96  (2499.80) 4050.78  (2696.92)
Day 1 Number Analyzed 265 participants 191 participants 177 participants 194 participants 562 participants
2513.84  (2649.60) 2283.24  (2805.64) 2083.09  (2684.72) 1600.21  (2326.52) 1984.43  (2621.80)
Day 2 Number Analyzed 241 participants 175 participants 160 participants 181 participants 516 participants
3688.96  (4071.55) 3470.11  (4148.24) 3114.71  (3588.75) 2584.89  (3621.66) 3049.40  (3809.45)
Day 3 Number Analyzed 214 participants 148 participants 147 participants 157 participants 452 participants
4179.02  (5054.24) 4020.24  (4939.49) 3684.97  (4584.27) 3212.04  (4932.67) 3630.48  (4825.32)
Day 4 Number Analyzed 201 participants 130 participants 130 participants 139 participants 399 participants
4347.58  (6027.04) 4094.19  (5122.49) 4633.22  (5855.47) 3880.32  (5643.93) 4195.31  (5546.47)
Day 5 Number Analyzed 173 participants 105 participants 114 participants 124 participants 343 participants
4600.67  (6723.02) 4307.39  (5636.37) 5126.22  (6910.78) 4079.52  (6367.01) 4497.16  (6342.44)
Day 6 Number Analyzed 154 participants 88 participants 92 participants 109 participants 289 participants
4750.10  (7322.08) 4312.81  (6564.90) 5263.21  (7595.18) 4224.47  (7163.95) 4582.04  (7121.18)
Day 7 Number Analyzed 139 participants 84 participants 87 participants 97 participants 268 participants
4978.66  (7803.61) 4418.66  (7263.42) 5628.59  (8471.78) 4425.98  (7977.33) 4814.08  (7919.51)
17.Secondary Outcome
Title Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days)
Hide Description [Not Specified]
Time Frame Baseline and Days 1-7
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed.
Arm/Group Title Placebo Selepressin 2.5 ng/kg/Min Selepressin 3.75 ng/kg/Min Selepressin 5.25 ng/kg/Min Selepressin Pooled
Hide Arm/Group Description:
Sterile 0.9% sodium chloride solution given as an infusion, was used as the placebo.
Starting dose: 1.7 ng/kg/min selepressin; Maximum dose: 2.5 ng/kg/min selepressin, given as an infusion.
Starting dose: 2.5 ng/kg/min selepressin; Maximum dose: 3.75 ng/kg/min selepressin, given as an infusion.
Starting dose: 3.5 ng/kg/min selepressin; Maximum dose: 5.25 ng/kg/min selepressin, given as an infusion.
All selepressin arms pooled together and treated as a single arm.
Overall Number of Participants Analyzed 266 191 177 194 562
Mean (Standard Deviation)
Unit of Measure: mL/h
Baseline Number Analyzed 265 participants 187 participants 177 participants 194 participants 558 participants
73.726  (94.7641) 72.944  (82.3338) 74.530  (92.8984) 83.773  (86.5417) 77.212  (87.2301)
Day 1 Number Analyzed 265 participants 191 participants 177 participants 194 participants 562 participants
85.277  (70.3224) 101.270  (80.4142) 94.290  (70.9804) 104.049  (75.8876) 100.031  (75.9501)
Day 2 Number Analyzed 241 participants 175 participants 160 participants 181 participants 516 participants
88.425  (61.2134) 89.404  (64.9307) 88.210  (59.6632) 92.400  (61.8536) 90.085  (62.1593)
Day 3 Number Analyzed 214 participants 148 participants 147 participants 157 participants 452 participants
104.124  (67.7586) 104.833  (66.4533) 85.403  (61.5660) 97.312  (67.8895) 95.902  (65.7529)
Day 4 Number Analyzed 201 participants 130 participants 130 participants 139 participants 399 participants
110.078  (73.3563) 103.459  (69.8165) 92.311  (65.0558) 102.859  (64.2044) 99.618  (66.3843)
Day 5 Number Analyzed 173 participants 105 participants 114 participants 124 participants 343 participants
116.732  (65.1159) 110.129  (65.7571) 100.581  (75.5667) 117.152  (68.3988) 109.494  (70.2288)
Day 6 Number Analyzed 154 participants 88 participants 92 participants 109 participants 289 participants
119.087  (65.7102) 126.512  (83.3418) 116.799  (79.3092) 118.269  (72.2910) 120.311  (77.8633)
Day 7 Number Analyzed 139 participants 84 participants 87 participants 97 participants 268 participants
116.082  (65.9402) 121.751  (68.1265) 111.499  (72.8493) 114.284  (69.5828) 115.720  (70.0786)
18.Secondary Outcome
Title Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days)
Hide Description Cumulative urinary output (absolute values) will be presented until ICU discharge (for a maximum of 7 Days).
Time Frame Baseline and Days 1-7
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed.
Arm/Group Title Placebo Selepressin 2.5 ng/kg/Min Selepressin 3.75 ng/kg/Min Selepressin 5.25 ng/kg/Min Selepressin Pooled
Hide Arm/Group Description:
Sterile 0.9% sodium chloride solution given as an infusion, was used as the placebo.
Starting dose: 1.7 ng/kg/min selepressin; Maximum dose: 2.5 ng/kg/min selepressin, given as an infusion.
Starting dose: 2.5 ng/kg/min selepressin; Maximum dose: 3.75 ng/kg/min selepressin, given as an infusion.
Starting dose: 3.5 ng/kg/min selepressin; Maximum dose: 5.25 ng/kg/min selepressin, given as an infusion.
All selepressin arms pooled together and treated as a single arm.
Overall Number of Participants Analyzed 266 191 177 194 562
Mean (Standard Deviation)
Unit of Measure: mL
Baseline Number Analyzed 265 participants 187 participants 177 participants 194 participants 558 participants
888.834  (1197.4426) 898.056  (1020.7890) 947.843  (1264.9054) 1017.646  (1076.2691) 955.426  (1121.3215)
Day 1 Number Analyzed 265 participants 191 participants 177 participants 194 participants 562 participants
2046.658  (1687.7381) 2430.485  (1929.9400) 2262.948  (1703.5290) 2497.173  (1821.3014) 2400.740  (1822.8019)
Day 2 Number Analyzed 241 participants 175 participants 160 participants 181 participants 516 participants
4343.786  (2909.9212) 4702.538  (3199.5558) 4534.714  (2825.1740) 4814.544  (3091.7350) 4689.788  (3045.8065)
Day 3 Number Analyzed 214 participants 148 participants 147 participants 157 participants 452 participants
6885.176  (4100.2125) 7527.805  (4401.3731) 6587.704  (3849.2099) 7322.964  (4322.9651) 7150.914  (4211.3049)
Day 4 Number Analyzed 201 participants 130 participants 130 participants 139 participants 399 participants
9501.722  (5247.5530) 10239.275  (5486.1180) 8786.522  (5086.7347) 9851.841  (5478.3671) 9630.976  (5377.6356)
Day 5 Number Analyzed 173 participants 105 participants 114 participants 124 participants 343 participants
12600.503  (6293.7322) 13219.597  (6695.6766) 11132.418  (6230.4688) 12795.773  (6400.6821) 12372.680  (6480.0818)
Day 6 Number Analyzed 154 participants 88 participants 92 participants 109 participants 289 participants
15159.980  (7264.4502) 16354.712  (7864.2281) 14522.098  (7391.7707) 15674.783  (7202.3158) 15514.875  (7479.2644)
Day 7 Number Analyzed 139 participants 84 participants 87 participants 97 participants 268 participants
17817.979  (8226.0238) 19269.682  (9081.2013) 17034.774  (8635.0531) 18380.119  (8479.7547) 18222.202  (8736.1728)
19.Secondary Outcome
Title Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed.
Arm/Group Title Placebo Selepressin 2.5 ng/kg/Min Selepressin 3.75 ng/kg/Min Selepressin 5.25 ng/kg/Min Selepressin Pooled
Hide Arm/Group Description:
Sterile 0.9% sodium chloride solution given as an infusion, was used as the placebo.
Starting dose: 1.7 ng/kg/min selepressin; Maximum dose: 2.5 ng/kg/min selepressin, given as an infusion.
Starting dose: 2.5 ng/kg/min selepressin; Maximum dose: 3.75 ng/kg/min selepressin, given as an infusion.
Starting dose: 3.5 ng/kg/min selepressin; Maximum dose: 5.25 ng/kg/min selepressin, given as an infusion.
All selepressin arms pooled together and treated as a single arm.
Overall Number of Participants Analyzed 266 191 177 194 562
Mean (Standard Deviation)
Unit of Measure: score on a scale
EQ VAS score (Baseline) Number Analyzed 166 participants 109 participants 108 participants 129 participants 346 participants
69.2  (21.13) 69.9  (21.69) 67.0  (21.60) 67.4  (22.83) 68.1  (22.07)
EQ VAS score (Day 30) Number Analyzed 130 participants 90 participants 77 participants 88 participants 255 participants
59.4  (21.21) 54.7  (21.12) 53.8  (19.63) 53.9  (23.99) 54.2  (21.65)
EQ VAS score (Day 60) Number Analyzed 132 participants 92 participants 82 participants 87 participants 261 participants
64.5  (20.58) 62.6  (20.92) 62.6  (18.94) 63.8  (20.30) 63.0  (20.04)
EQ VAS score (Day 90) Number Analyzed 130 participants 87 participants 80 participants 87 participants 254 participants
68.2  (19.61) 65.9  (20.70) 67.0  (17.50) 68.1  (18.63) 67.0  (18.98)
EQ VAS score (Day 180) Number Analyzed 129 participants 88 participants 85 participants 86 participants 259 participants
72.6  (20.07) 71.2  (18.55) 67.4  (21.39) 69.7  (20.29) 69.5  (20.08)
EQ-5D-5L index score (Baseline) Number Analyzed 168 participants 110 participants 109 participants 132 participants 351 participants
0.7305  (0.25098) 0.7648  (0.22393) 0.7576  (0.23070) 0.7380  (0.22152) 0.7525  (0.22481)
EQ-5D-5L index score (Day 30) Number Analyzed 130 participants 92 participants 80 participants 91 participants 263 participants
0.5706  (0.29463) 0.5600  (0.27848) 0.5089  (0.29004) 0.5283  (0.33580) 0.5335  (0.30245)
EQ-5D-5L index score (Day 60) Number Analyzed 133 participants 94 participants 83 participants 89 participants 266 participants
0.6707  (0.26160) 0.6788  (0.22544) 0.6719  (0.21777) 0.6746  (0.25391) 0.6753  (0.23222)
EQ-5D-5L index score (Day 90) Number Analyzed 131 participants 88 participants 81 participants 89 participants 258 participants
0.7207  (0.22523) 0.7018  (0.26544) 0.7290  (0.21608) 0.6810  (0.24960) 0.7032  (0.24515)
EQ-5D-5L index score (Day 180) Number Analyzed 130 participants 89 participants 88 participants 87 participants 264 participants
0.7627  (0.22170) 0.7572  (0.19803) 0.7409  (0.19813) 0.7435  (0.23729) 0.7472  (0.21112)
20.Secondary Outcome
Title Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed.
Arm/Group Title Placebo Selepressin 2.5 ng/kg/Min Selepressin 3.75 ng/kg/Min Selepressin 5.25 ng/kg/Min Selepressin Pooled
Hide Arm/Group Description:
Sterile 0.9% sodium chloride solution given as an infusion, was used as the placebo.
Starting dose: 1.7 ng/kg/min selepressin; Maximum dose: 2.5 ng/kg/min selepressin, given as an infusion.
Starting dose: 2.5 ng/kg/min selepressin; Maximum dose: 3.75 ng/kg/min selepressin, given as an infusion.
Starting dose: 3.5 ng/kg/min selepressin; Maximum dose: 5.25 ng/kg/min selepressin, given as an infusion.
All selepressin arms pooled together and treated as a single arm.
Overall Number of Participants Analyzed 266 191 177 194 562
Mean (Standard Deviation)
Unit of Measure: Quality-adjusted life-year
EQ-5D-5L QALY (Day 30) Number Analyzed 125 participants 86 participants 74 participants 86 participants 246 participants
0.036  (0.0558) 0.039  (0.0448) 0.033  (0.0388) 0.030  (0.0501) 0.034  (0.0451)
EQ-5D-5L QALY (Day 60) Number Analyzed 126 participants 84 participants 75 participants 82 participants 241 participants
0.088  (0.0683) 0.093  (0.0588) 0.085  (0.0548) 0.084  (0.0643) 0.087  (0.0595)
EQ-5D-5L QALY (Day 90) Number Analyzed 123 participants 80 participants 74 participants 82 participants 236 participants
0.144  (0.0819) 0.146  (0.0725) 0.145  (0.0670) 0.139  (0.0760) 0.143  (0.0718)
EQ-5D-5L QALY (Day 180) Number Analyzed 120 participants 80 participants 80 participants 81 participants 241 participants
0.330  (0.1174) 0.338  (0.1239) 0.329  (0.1011) 0.319  (0.1155) 0.328  (0.1137)
Time Frame All-cause mortality, defined as the percentage of subjects that have died regardless of cause, was recorded up to Day 180. Treatment-emergent adverse events (TEAEs) were collected during the treatment period, i.e., TEAEs occurring after IMP infusion to within 12 hours after the IMP infusion was stopped.
Adverse Event Reporting Description All treated subjects were included in the safety analysis set and were analyzed according to the actual treatment received.
 
Arm/Group Title Placebo Selepressin 2.5 ng/kg/Min Selepressin 3.75 ng/kg/Min Selepressin 5.25 ng/kg/Min Selepressin Pooled
Hide Arm/Group Description Sterile 0.9% sodium chloride solution given as an infusion, was used as the placebo. Starting dose: 1.7 ng/kg/min selepressin; Maximum dose: 2.5 ng/kg/min selepressin, given as an infusion. Starting dose: 2.5 ng/kg/min selepressin; Maximum dose: 3.75 ng/kg/min selepressin, given as an infusion. Starting dose: 3.5 ng/kg/min selepressin; Maximum dose: 5.25 ng/kg/min selepressin, given as an infusion. All selepressin arms pooled together and treated as a single arm.
All-Cause Mortality
Placebo Selepressin 2.5 ng/kg/Min Selepressin 3.75 ng/kg/Min Selepressin 5.25 ng/kg/Min Selepressin Pooled
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   116/266 (43.61%)      80/191 (41.88%)      76/177 (42.94%)      85/194 (43.81%)      241/562 (42.88%)    
Hide Serious Adverse Events
Placebo Selepressin 2.5 ng/kg/Min Selepressin 3.75 ng/kg/Min Selepressin 5.25 ng/kg/Min Selepressin Pooled
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   85/266 (31.95%)      57/191 (29.84%)      65/177 (36.72%)      57/194 (29.38%)      179/562 (31.85%)    
Blood and lymphatic system disorders           
Anaemia  1  0/266 (0.00%)  0 0/191 (0.00%)  0 0/177 (0.00%)  0 1/194 (0.52%)  1 1/562 (0.18%)  1
Disseminated intravascular coagulation  1  0/266 (0.00%)  0 0/191 (0.00%)  0 0/177 (0.00%)  0 1/194 (0.52%)  1 1/562 (0.18%)  1
Haemolysis  1  1/266 (0.38%)  1 0/191 (0.00%)  0 0/177 (0.00%)  0 0/194 (0.00%)  0 0/562 (0.00%)  0
Splenic necrosis  1  0/266 (0.00%)  0 0/191 (0.00%)  0 1/177 (0.56%)  1 0/194 (0.00%)  0 1/562 (0.18%)  1
Thrombocytopenia  1  0/266 (0.00%)  0 0/191 (0.00%)  0 1/177 (0.56%)  1 0/194 (0.00%)  0 1/562 (0.18%)  1
Cardiac disorders           
Cardiac arrest  1  3/266 (1.13%)  3 5/191 (2.62%)  7 5/177 (2.82%)  6 1/194 (0.52%)  1 11/562 (1.96%)  14
Myocardial ischaemia  1  1/266 (0.38%)  1 1/191 (0.52%)  1 4/177 (2.26%)  4 0/194 (0.00%)  0 5/562 (0.89%)  5
Acute myocardial infarction  1  0/266 (0.00%)  0 2/191 (1.05%)  2 1/177 (0.56%)  1 0/194 (0.00%)  0 3/562 (0.53%)  3
Cyanosis  1  0/266 (0.00%)  0 0/191 (0.00%)  0 1/177 (0.56%)  1 2/194 (1.03%)  2 3/562 (0.53%)  3
Pulseless electrical activity  1  0/266 (0.00%)  0 0/191 (0.00%)  0 2/177 (1.13%)  2 1/194 (0.52%)  1 3/562 (0.53%)  3
Cardiac failure  1  0/266 (0.00%)  0 0/191 (0.00%)  0 0/177 (0.00%)  0 2/194 (1.03%)  2 2/562 (0.36%)  2
Cardiogenic shock  1  1/266 (0.38%)  1 1/191 (0.52%)  1 1/177 (0.56%)  1 0/194 (0.00%)  0 2/562 (0.36%)  2
Supraventricular tachycardia  1  0/266 (0.00%)  0 0/191 (0.00%)  0 1/177 (0.56%)  1 1/194 (0.52%)  1 2/562 (0.36%)  2
Acute coronary syndrome  1  1/266 (0.38%)  1 1/191 (0.52%)  1 0/177 (0.00%)  0 0/194 (0.00%)  0 1/562 (0.18%)  1
Atrial fibrillation  1  1/266 (0.38%)  1 0/191 (0.00%)  0 0/177 (0.00%)  0 0/194 (0.00%)  0 0/562 (0.00%)  0
Defect conduction intraventricular  1  0/266 (0.00%)  0 1/191 (0.52%)  1 0/177 (0.00%)  0 0/194 (0.00%)  0 1/562 (0.18%)  1
Myocardial depression  1  0/266 (0.00%)  0 0/191 (0.00%)  0 0/177 (0.00%)  0 1/194 (0.52%)  1 1/562 (0.18%)  1
Myocardial infarction  1  1/266 (0.38%)  1 0/191 (0.00%)  0 0/177 (0.00%)  0 1/194 (0.52%)  1 1/562 (0.18%)  1
Myocardial stunning  1  0/266 (0.00%)  0 0/191 (0.00%)  0 1/177 (0.56%)  1 0/194 (0.00%)  0 1/562 (0.18%)  1
Right ventricular failure  1  1/266 (0.38%)  1 0/191 (0.00%)  0 0/177 (0.00%)  0 0/194 (0.00%)  0 0/562 (0.00%)  0
Sinus bradycardia  1  0/266 (0.00%)  0 0/191 (0.00%)  0 1/177 (0.56%)  1 0/194 (0.00%)  0 1/562 (0.18%)  1
Tachycardia  1  1/266 (0.38%)  1 0/191 (0.00%)  0 0/177 (0.00%)  0 0/194 (0.00%)  0 0/562 (0.00%)  0
Ventricular arrhythmia  1  1/266 (0.38%)  1 0/191 (0.00%)  0 0/177 (0.00%)  0 0/194 (0.00%)  0 0/562 (0.00%)  0
Ventricular fibrillation  1  1/266 (0.38%)  1 0/191 (0.00%)  0 0/177 (0.00%)  0 0/194 (0.00%)  0 0/562 (0.00%)  0
Ventricular tachycardia  1  1/266 (0.38%)  1 0/191 (0.00%)  0 0/177 (0.00%)  0 1/194 (0.52%)  1 1/562 (0.18%)  1
Gastrointestinal disorders           
Intestinal ischaemia  1  3/266 (1.13%)  3 4/191 (2.09%)  4 1/177 (0.56%)  1 2/194 (1.03%)  3 7/562 (1.25%)  8
Abdominal compartment syndrome  1  0/266 (0.00%)  0 0/191 (0.00%)  0 0/177 (0.00%)  0 1/194 (0.52%)  1 1/562 (0.18%)  1
Colitis ischaemic  1  0/266 (0.00%)  0 0/191 (0.00%)  0 1/177 (0.56%)  1 0/194 (0.00%)  0 1/562 (0.18%)  1
Colonic fistula  1  0/266 (0.00%)  0 0/191 (0.00%)  0 1/177 (0.56%)  1 0/194 (0.00%)  0 1/562 (0.18%)  1
Duodenal perforation  1  1/266 (0.38%)  1 0/191 (0.00%)  0 0/177 (0.00%)  0 0/194 (0.00%)  0 0/562 (0.00%)  0
Gastric haemorrhage  1  1/266 (0.38%)  1 0/191 (0.00%)  0 0/177 (0.00%)  0 0/194 (0.00%)  0 0/562 (0.00%)  0
Gastrointestinal ischaemia  1  1/266 (0.38%)  1 0/191 (0.00%)  0 0/177 (0.00%)  0 0/194 (0.00%)  0 0/562 (0.00%)  0
Gastrointestinal necrosis  1  0/266 (0.00%)  0 1/191 (0.52%)  1 0/177 (0.00%)  0 0/194 (0.00%)  0 1/562 (0.18%)  1
Ileus  1  0/266 (0.00%)  0 0/191 (0.00%)  0 1/177 (0.56%)  1 0/194 (0.00%)  0 1/562 (0.18%)  1
Large intestine perforation  1  0/266 (0.00%)  0 0/191 (0.00%)  0 1/177 (0.56%)  1 0/194 (0.00%)  0 1/562 (0.18%)  1
Peritoneal haemorrhage  1  1/266 (0.38%)  1 0/191 (0.00%)  0 0/177 (0.00%)  0 0/194 (0.00%)  0 0/562 (0.00%)  0
General disorders           
Multiple organ dysfunction syndrome  1  24/266 (9.02%)  24 10/191 (5.24%)  10 17/177 (9.60%)  17 12/194 (6.19%)  12 39/562 (6.94%)  39
Catheter site haemorrhage  1  0/266 (0.00%)  0 1/191 (0.52%)  1 0/177 (0.00%)  0 0/194 (0.00%)  0 1/562 (0.18%)  1
Disease progression  1  0/266 (0.00%)  0 1/191 (0.52%)  1 0/177 (0.00%)  0 0/194 (0.00%)  0 1/562 (0.18%)  1
General physical health deterioration  1  0/266 (0.00%)  0 1/191 (0.52%)  1 0/177 (0.00%)  0 0/194 (0.00%)  0 1/562 (0.18%)  1
Hyperthermia  1  1/266 (0.38%)  1 0/191 (0.00%)  0 0/177 (0.00%)  0 0/194 (0.00%)  0 0/562 (0.00%)  0
Organ failure  1  0/266 (0.00%)  0 0/191 (0.00%)  0 0/177 (0.00%)  0 1/194 (0.52%)  1 1/562 (0.18%)  1
Hepatobiliary disorders           
Hepatic failure  1  1/266 (0.38%)  1 1/191 (0.52%)  1 1/177 (0.56%)  1 0/194 (0.00%)  0 2/562 (0.36%)  2
Acute hepatic failure  1  0/266 (0.00%)  0 1/191 (0.52%)  1 0/177 (0.00%)  0 0/194 (0.00%)  0 1/562 (0.18%)  1
Cholecystitis  1  0/266 (0.00%)  0 0/191 (0.00%)  0 1/177 (0.56%)  1 0/194 (0.00%)  0 1/562 (0.18%)  1
Chronic hepatic failure  1  1/266 (0.38%)  1 0/191 (0.00%)  0 0/177 (0.00%)  0 0/194 (0.00%)  0 0/562 (0.00%)  0
Gallbladder disorder  1  0/266 (0.00%)  0 0/191 (0.00%)  0 0/177 (0.00%)  0 1/194 (0.52%)  1 1/562 (0.18%)  1
Hepatitis acute  1  0/266 (0.00%)  0 1/191 (0.52%)  1 0/177 (0.00%)  0 0/194 (0.00%)  0 1/562 (0.18%)  1
Hepatocellular injury  1  0/266 (0.00%)  0 1/191 (0.52%)  1 0/177 (0.00%)  0 0/194 (0.00%)  0 1/562 (0.18%)  1
Ischaemic hepatitis  1  0/266 (0.00%)  0 0/191 (0.00%)  0 0/177 (0.00%)  0 1/194 (0.52%)  1 1/562 (0.18%)  1
Infections and infestations           
Septic shock  1  15/266 (5.64%)  15 10/191 (5.24%)  10 12/177 (6.78%)  12 8/194 (4.12%)  8 30/562 (5.34%)  30
Pneumonia  1  4/266 (1.50%)  4 2/191 (1.05%)  2 2/177 (1.13%)  2 0/194 (0.00%)  0 4/562 (0.71%)  4
Sepsis  1  1/266 (0.38%)  1 0/191 (0.00%)  0 1/177 (0.56%)  1 3/194 (1.55%)  3 4/562 (0.71%)  4
Endocarditis  1  0/266 (0.00%)  0 1/191 (0.52%)  1 1/177 (0.56%)  1 1/194 (0.52%)  1 3/562 (0.53%)  3
Abscess  1  0/266 (0.00%)  0 0/191 (0.00%)  0 0/177 (0.00%)  0 1/194 (0.52%)  1 1/562 (0.18%)  1
Arthritis infective  1  0/266 (0.00%)  0 1/191 (0.52%)  1 0/177 (0.00%)  0 0/194 (0.00%)  0 1/562 (0.18%)  1
Cellulitis  1  0/266 (0.00%)  0 0/191 (0.00%)  0 0/177 (0.00%)  0 1/194 (0.52%)  1 1/562 (0.18%)  1
Device related sepsis  1  0/266 (0.00%)  0 0/191 (0.00%)  0 1/177 (0.56%)  1 0/194 (0.00%)  0 1/562 (0.18%)  1
Extradural abscess  1  0/266 (0.00%)  0 0/191 (0.00%)  0 0/177 (0.00%)  0 1/194 (0.52%)  1 1/562 (0.18%)  1
Klebsiella sepsis  1  0/266 (0.00%)  0 0/191 (0.00%)  0 1/177 (0.56%)  1 0/194 (0.00%)  0 1/562 (0.18%)  1
Necrotising fasciitis  1  0/266 (0.00%)  0 0/191 (0.00%)  0 0/177 (0.00%)  0 1/194 (0.52%)  1 1/562 (0.18%)  1
Peritonitis bacterial  1  0/266 (0.00%)  0 1/191 (0.52%)  1 0/177 (0.00%)  0 0/194 (0.00%)  0 1/562 (0.18%)  1
Injury, poisoning and procedural complications           
Anastomotic leak  1  0/266 (0.00%)  0 2/191 (1.05%)  2 0/177 (0.00%)  0 0/194 (0.00%)  0 2/562 (0.36%)  2
Endotracheal intubation complication  1  1/266 (0.38%)  1 0/191 (0.00%)  0 0/177 (0.00%)  0 0/194 (0.00%)  0 0/562 (0.00%)  0
Subarachnoid haemorrhage  1  0/266 (0.00%)  0 0/191 (0.00%)  0 0/177 (0.00%)  0 1/194 (0.52%)  1 1/562 (0.18%)  1
Traumatic haemothorax  1  0/266 (0.00%)  0 0/191 (0.00%)  0 1/177 (0.56%)  1 0/194 (0.00%)  0 1/562 (0.18%)  1
Investigations           
Cardiac output decreased  1  0/266 (0.00%)  0 0/191 (0.00%)  0 1/177 (0.56%)  1 0/194 (0.00%)  0 1/562 (0.18%)  1
Troponin I increased  1  1/266 (0.38%)  1 0/191 (0.00%)  0 0/177 (0.00%)  0 0/194 (0.00%)  0 0/562 (0.00%)  0
Troponin increased  1  0/266 (0.00%)  0 0/191 (0.00%)  0 0/177 (0.00%)  0 1/194 (0.52%)  1 1/562 (0.18%)  1
Metabolism and nutrition disorders           
Hyperkalaemia  1  1/266 (0.38%)  1 0/191 (0.00%)  0 1/177 (0.56%)  1 0/194 (0.00%)  0 1/562 (0.18%)  1
Hyperlactacidaemia  1  0/266 (0.00%)  0 1/191 (0.52%)  1 0/177 (0.00%)  0 0/194 (0.00%)  0 1/562 (0.18%)  1
Lactic acidosis  1  0/266 (0.00%)  0 0/191 (0.00%)  0 1/177 (0.56%)  1 0/194 (0.00%)  0 1/562 (0.18%)  1
Musculoskeletal and connective tissue disorders           
Fasciitis  1  1/266 (0.38%)  1 0/191 (0.00%)  0 0/177 (0.00%)  0 0/194 (0.00%)  0 0/562 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Lung adenocarcinoma  1  1/266 (0.38%)  1 0/191 (0.00%)  0 0/177 (0.00%)  0 0/194 (0.00%)  0 0/562 (0.00%)  0
Lung cancer metastatic  1  1/266 (0.38%)  1 0/191 (0.00%)  0 1/177 (0.56%)  1 0/194 (0.00%)  0 1/562 (0.18%)  1
Lymphoma  1  0/266 (0.00%)  0 0/191 (0.00%)  0 1/177 (0.56%)  1 0/194 (0.00%)  0 1/562 (0.18%)  1
Malignant neoplasm progression  1  0/266 (0.00%)  0 1/191 (0.52%)  1 0/177 (0.00%)  0 0/194 (0.00%)  0 1/562 (0.18%)  1
Metastatic carcinoma of the bladder  1  1/266 (0.38%)  1 0/191 (0.00%)  0 0/177 (0.00%)  0 0/194 (0.00%)  0 0/562 (0.00%)  0
Metastatic neoplasm  1  1/266 (0.38%)  1 0/191 (0.00%)  0 0/177 (0.00%)  0 0/194 (0.00%)  0 0/562 (0.00%)  0
Pancreatic carcinoma  1  0/266 (0.00%)  0 1/191 (0.52%)  1 0/177 (0.00%)  0 0/194 (0.00%)  0 1/562 (0.18%)  1
Nervous system disorders           
Encephalopathy  1  2/266 (0.75%)  2 0/191 (0.00%)  0 0/177 (0.00%)  0 1/194 (0.52%)  1 1/562 (0.18%)  1
Brain oedema  1  0/266 (0.00%)  0 0/191 (0.00%)  0 0/177 (0.00%)  0 1/194 (0.52%)  1 1/562 (0.18%)  1
Cerebral ischaemia  1  1/266 (0.38%)  1 1/191 (0.52%)  1 0/177 (0.00%)  0 0/194 (0.00%)  0 1/562 (0.18%)  1
Coma  1  0/266 (0.00%)  0 0/191 (0.00%)  0 0/177 (0.00%)  0 1/194 (0.52%)  1 1/562 (0.18%)  1
Vasculitis cerebral  1  1/266 (0.38%)  1 0/191 (0.00%)  0 0/177 (0.00%)  0 0/194 (0.00%)  0 0/562 (0.00%)  0
Renal and urinary disorders           
Acute kidney injury  1  5/266 (1.88%)  5 0/191 (0.00%)  0 2/177 (1.13%)  2 0/194 (0.00%)  0 2/562 (0.36%)  2
Renal failure  1  1/266 (0.38%)  1 1/191 (0.52%)  1 0/177 (0.00%)  0 2/194 (1.03%)  2 3/562 (0.53%)  3
Respiratory, thoracic and mediastinal disorders           
Acute respiratory distress syndrome  1  4/266 (1.50%)  4 3/191 (1.57%)  3 3/177 (1.69%)  3 1/194 (0.52%)  1 7/562 (1.25%)  7
Respiratory failure  1  3/266 (1.13%)  3 0/191 (0.00%)  0 1/177 (0.56%)  1 5/194 (2.58%)  5 6/562 (1.07%)  6
Hypoxia  1  0/266 (0.00%)  0 1/191 (0.52%)  1 2/177 (1.13%)  2 0/194 (0.00%)  0 3/562 (0.53%)  3
Acute respiratory failure  1  0/266 (0.00%)  0 0/191 (0.00%)  0 1/177 (0.56%)  1 0/194 (0.00%)  0 1/562 (0.18%)  1
Aspiration  1  1/266 (0.38%)  1 0/191 (0.00%)  0 0/177 (0.00%)  0 0/194 (0.00%)  0 0/562 (0.00%)  0
Mediastinal mass  1  0/266 (0.00%)  0 1/191 (0.52%)  1 0/177 (0.00%)  0 0/194 (0.00%)  0 1/562 (0.18%)  1
Pulmonary fibrosis  1  0/266 (0.00%)  0 1/191 (0.52%)  1 0/177 (0.00%)  0 0/194 (0.00%)  0 1/562 (0.18%)  1
Pulmonary haemorrhage  1  1/266 (0.38%)  1 0/191 (0.00%)  0 0/177 (0.00%)  0 0/194 (0.00%)  0 0/562 (0.00%)  0
Skin and subcutaneous tissue disorders           
Skin discolouration  1  1/266 (0.38%)  1 2/191 (1.05%)  2 2/177 (1.13%)  2 1/194 (0.52%)  1 5/562 (0.89%)  5
Vascular disorders           
Peripheral ischaemia  1  1/266 (0.38%)  1 1/191 (0.52%)  1 4/177 (2.26%)  4 2/194 (1.03%)  2 7/562 (1.25%)  7
Shock  1  4/266 (1.50%)  4 1/191 (0.52%)  1 1/177 (0.56%)  1 3/194 (1.55%)  3 5/562 (0.89%)  5
Hypotension  1  0/266 (0.00%)  0 0/191 (0.00%)  0 1/177 (0.56%)  1 3/194 (1.55%)  3 4/562 (0.71%)  4
Shock haemorrhagic  1  0/266 (0.00%)  0 0/191 (0.00%)  0 1/177 (0.56%)  1 1/194 (0.52%)  1 2/562 (0.36%)  2
Vasoconstriction  1  0/266 (0.00%)  0 1/191 (0.52%)  1 1/177 (0.56%)  1 0/194 (0.00%)  0 2/562 (0.36%)  2
Circulatory collapse  1  0/266 (0.00%)  0 1/191 (0.52%)  1 0/177 (0.00%)  0 0/194 (0.00%)  0 1/562 (0.18%)  1
Distributive shock  1  1/266 (0.38%)  1 0/191 (0.00%)  0 0/177 (0.00%)  0 0/194 (0.00%)  0 0/562 (0.00%)  0
Dry gangrene  1  0/266 (0.00%)  0 0/191 (0.00%)  0 1/177 (0.56%)  1 0/194 (0.00%)  0 1/562 (0.18%)  1
Extremity necrosis  1  0/266 (0.00%)  0 0/191 (0.00%)  0 0/177 (0.00%)  0 1/194 (0.52%)  1 1/562 (0.18%)  1
Hypertension  1  1/266 (0.38%)  1 0/191 (0.00%)  0 1/177 (0.56%)  1 0/194 (0.00%)  0 1/562 (0.18%)  1
Ischaemia  1  0/266 (0.00%)  0 0/191 (0.00%)  0 0/177 (0.00%)  0 1/194 (0.52%)  1 1/562 (0.18%)  1
Poor peripheral circulation  1  1/266 (0.38%)  1 0/191 (0.00%)  0 0/177 (0.00%)  0 0/194 (0.00%)  0 0/562 (0.00%)  0
Thrombosis  1  0/266 (0.00%)  0 0/191 (0.00%)  0 0/177 (0.00%)  0 1/194 (0.52%)  1 1/562 (0.18%)  1
1
Term from vocabulary, MedDRA (20.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Selepressin 2.5 ng/kg/Min Selepressin 3.75 ng/kg/Min Selepressin 5.25 ng/kg/Min Selepressin Pooled
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   94/266 (35.34%)      54/191 (28.27%)      63/177 (35.59%)      60/194 (30.93%)      177/562 (31.49%)    
Blood and lymphatic system disorders           
Thrombocytopenia  1  12/266 (4.51%)  13 9/191 (4.71%)  9 10/177 (5.65%)  10 11/194 (5.67%)  11 30/562 (5.34%)  30
Anaemia  1  24/266 (9.02%)  25 12/191 (6.28%)  13 6/177 (3.39%)  6 7/194 (3.61%)  7 25/562 (4.45%)  26
Cardiac disorders           
Atrial fibrillation  1  30/266 (11.28%)  43 22/191 (11.52%)  23 24/177 (13.56%)  27 22/194 (11.34%)  29 68/562 (12.10%)  79
Injury, poisoning and procedural complications           
Expired product administered  1  50/266 (18.80%)  94 26/191 (13.61%)  48 29/177 (16.38%)  47 31/194 (15.98%)  62 86/562 (15.30%)  157
Metabolism and nutrition disorders           
Hypokalaemia  1  4/266 (1.50%)  4 5/191 (2.62%)  5 9/177 (5.08%)  9 4/194 (2.06%)  4 18/562 (3.20%)  18
1
Term from vocabulary, MedDRA (20.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The only disclosure restriction on the PI is that the sponsor can review the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the sponsor or confidential to the sponsor. Comments will be given within four weeks from receipt of the draft manuscript. Additional time may be required to allow Ferring to seek patent protection of the invention.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Clinical Compliance
Organization: Ferring Pharmaceuticals
Phone: +1 833-548-1402
EMail: DK0-Disclosure@ferring.com
Layout table for additonal information
Responsible Party: Ferring Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02508649    
Other Study ID Numbers: 000133
2014-003973-41 ( EudraCT Number )
First Submitted: July 17, 2015
First Posted: July 27, 2015
Results First Submitted: September 27, 2020
Results First Posted: April 6, 2021
Last Update Posted: April 6, 2021