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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-003973-41 | EudraCT Number |
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Terminated due to futility
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator |
| |
| Selepressin 1 | Experimental | Starting dose 1.7 ng/kg/min |
|
| Selepressin 2 | Experimental | Starting dose 2.5 ng/kg/min |
|
| Selepressin 3 | Experimental | Starting dose 3.5 ng/kg/min |
|
| Selepressin 4 | Experimental | Starting dose 5.0 ng/kg/min The highest dosing regimen of selepressin was not investigated in the trial as the desired primary outcome for selepressin 3 arm was not achieved, and the trial was terminated for futility. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| selepressin | Drug |
| ||
| placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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:
| Up to Day 30 |
| Measure | Description | Time Frame |
|---|---|---|
| All-cause Mortality | All-cause mortality defined as the percentage of subjects that have died, regardless of cause. | At Day 90 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Development Support | Ferring Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Memorial Hospital | Colorado Springs | Colorado | 80909 | United States | ||
| Eastern Idaho Regional Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31577035 | Derived | Laterre PF, Berry SM, Blemings A, Carlsen JE, Francois B, Graves T, Jacobsen K, Lewis RJ, Opal SM, Perner A, Pickkers P, Russell JA, Windelov NA, Yealy DM, Asfar P, Bestle MH, Muller G, Bruel C, Brule N, Decruyenaere J, Dive AM, Dugernier T, Krell K, Lefrant JY, Megarbane B, Mercier E, Mira JP, Quenot JP, Rasmussen BS, Thorsen-Meyer HC, Vander Laenen M, Vang ML, Vignon P, Vinatier I, Wichmann S, Wittebole X, Kjolbye AL, Angus DC; SEPSIS-ACT Investigators. Effect of Selepressin vs Placebo on Ventilator- and Vasopressor-Free Days in Patients With Septic Shock: The SEPSIS-ACT Randomized Clinical Trial. JAMA. 2019 Oct 15;322(15):1476-1485. doi: 10.1001/jama.2019.14607. | |
| 29388815 |
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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.
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).
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Sterile 0.9% sodium chloride solution given as an infusion, was used as the placebo. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 8, 2016 | Sep 27, 2020 |
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| Drug |
|
| Up to Day 30 |
| 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). | Up to Day 30 |
| 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. | Up to Day 30 |
| 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. | Up to Day 30 |
| 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. | Up to Day 30 |
| 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. | Up to Day 30 |
| 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. | Up to Day 30 |
| 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. | Up to Day 90 |
| 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). | Days 1, 3, and 7 or discharge from ICU |
| 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. | Up to Day 7 and Day 30 |
| 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. | Up to Day 30 |
| 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. | At Day 30 and Day 180 |
| 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). | Baseline and Days 1-7 |
| 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). | Baseline and Days 1-7 |
| 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) | Cumulative urinary output (absolute values) will be presented until ICU discharge (for a maximum of 7 Days). | Baseline and Days 1-7 |
| 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. | Baseline and Days 30, 60, 90 and 180 |
| 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. | Days 30, 60, 90 and 180 |
| Idaho Falls |
| Idaho |
| 83404 |
| United States |
| Rush University Medical Center | Chicago | Illinois | 60612 | United States |
| Northshore University Healthsystem Research Institute | Evanston | Illinois | 60201 | United States |
| Stormont Vail Health Care | Topeka | Kansas | 66604 | United States |
| Baystate Medical Center | Springfield | Massachusetts | 01199 | United States |
| Henry Ford Hospital | Detroit | Michigan | United States |
| HealthPartners Speciality Clinics | Saint Paul | Minnesota | 55101 | United States |
| University of Nebraska Medical Center | Omaha | Nebraska | 68198 | United States |
| Cooper University Hospital | Camden | New Jersey | 08103 | United States |
| Wake Forest University School of Medicine | Winston-Salem | North Carolina | 27157 | United States |
| Ohio State University | Columbus | Ohio | 43210-1252 | United States |
| Remington Davis Inc | Columbus | Ohio | 43215 | United States |
| St Vincent Mercy Medical Center | Toledo | Ohio | 43608 | United States |
| University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | United States |
| Temple University Hospital | Philadelphia | Pennsylvania | United States |
| University of Pittsburgh Medical Center | Pittsburgh | Pennsylvania | United States |
| Cliniques Universitaires Saint-Luc (there may be other sites in this country) | Brussels | Belgium |
| Aalborg Universitetshospital (there may be other sites in this country) | Aalborg | Denmark |
| Centre Hospitalier et Universitaire de Limoges (there may be other sites in this country) | Limoges | France |
| Radboud University Nijmegen Medical Centre (there may be other sites in this country) | Nijmegen | Netherlands |
| Derived |
| Lewis RJ, Angus DC, Laterre PF, Kjolbye AL, van der Meulen E, Blemings A, Graves T, Russell JA, Carlsen JE, Jacobsen K, Yealy DM, Opal SM, Windelov NA, Francois B, Perner A, Pickkers P, Berry SM. Rationale and Design of an Adaptive Phase 2b/3 Clinical Trial of Selepressin for Adults in Septic Shock. Selepressin Evaluation Programme for Sepsis-induced Shock-Adaptive Clinical Trial. Ann Am Thorac Soc. 2018 Feb;15(2):250-257. doi: 10.1513/AnnalsATS.201708-669SD. |
| FG002 | 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. |
| FG003 | 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. |
| Dosed |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
The full analysis set (FAS) comprised of all the subjects who were enrolled (i.e. randomized [as planned]) and dosed.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Sterile 0.9% sodium chloride solution given as an infusion, was used as the placebo. |
| BG001 | 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. |
| BG002 | 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. |
| BG003 | 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. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| ||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
| |||||||||||
| Baseline BMI | 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. | Mean | Standard Deviation | kg/m^2 |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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:
| 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. | Posted | Least Squares Mean | 95% Confidence Interval | days | Up to Day 30 |
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| Secondary | All-cause Mortality | All-cause mortality defined as the percentage of subjects that have died, regardless of cause. | 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. | Posted | Number | percentage of subjects | At Day 90 |
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| 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | days | Up to Day 30 |
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| 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). | 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. | Posted | Least Squares Mean | 95% Confidence Interval | days | Up to Day 30 |
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| 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. | The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed. | Posted | Median | Inter-Quartile Range | days | Up to Day 30 |
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| 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. | The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed. | Posted | Median | Inter-Quartile Range | days | Up to Day 30 |
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| 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. | The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed. | Posted | Median | Inter-Quartile Range | days | Up to Day 30 |
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| 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. | The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed. | Posted | Median | Inter-Quartile Range | days | Up to Day 30 |
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| 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. | The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed. | Posted | Count of Participants | Participants | Up to Day 30 |
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| 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. | The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed. | Posted | Mean | Standard Deviation | days | Up to Day 90 |
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| 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). | 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. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Days 1, 3, and 7 or discharge from ICU |
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| 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. | 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. | Posted | Number | 95% Confidence Interval | percentage of subjects | Up to Day 7 and Day 30 |
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| 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. | The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed. | Posted | Median | Inter-Quartile Range | days | Up to Day 30 |
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| 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. | The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed. | Posted | Count of Participants | Participants | At Day 30 and Day 180 |
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| 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). | The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed. | Posted | Mean | Standard Deviation | mL/h | Baseline and Days 1-7 |
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| 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). | The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed. | Posted | Mean | Standard Deviation | mL | Baseline and Days 1-7 |
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| Secondary | Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days) | The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed. | Posted | Mean | Standard Deviation | mL/h | Baseline and Days 1-7 |
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| 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). | The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed. | Posted | Mean | Standard Deviation | mL | Baseline and Days 1-7 |
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| 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. | The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Days 30, 60, 90 and 180 |
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| 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. | The FAS comprised of all subjects who were enrolled (i.e. randomized [as planned]) and dosed. | Posted | Mean | Standard Deviation | Quality-adjusted life-year | Days 30, 60, 90 and 180 |
|
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.
All treated subjects were included in the safety analysis set and were analyzed according to the actual treatment received.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Sterile 0.9% sodium chloride solution given as an infusion, was used as the placebo. | 116 | 266 | 85 | 266 | 94 | 266 |
| EG001 | 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. | 80 | 191 | 57 | 191 | 54 | 191 |
| EG002 | 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. | 76 | 177 | 65 | 177 | 63 | 177 |
| EG003 | 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. | 85 | 194 | 57 | 194 | 60 | 194 |
| EG004 | Selepressin Pooled | All selepressin arms pooled together and treated as a single arm. | 241 | 562 | 179 | 562 | 177 | 562 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Disseminated intravascular coagulation | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Haemolysis | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Splenic necrosis | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Cardiac arrest | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Myocardial ischaemia | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Cyanosis | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Pulseless electrical activity | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Cardiogenic shock | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Supraventricular tachycardia | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Acute coronary syndrome | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Defect conduction intraventricular | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Myocardial depression | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Myocardial stunning | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Right ventricular failure | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Sinus bradycardia | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Ventricular arrhythmia | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Ventricular fibrillation | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Ventricular tachycardia | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Intestinal ischaemia | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Abdominal compartment syndrome | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Colitis ischaemic | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Colonic fistula | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Duodenal perforation | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Gastric haemorrhage | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Gastrointestinal ischaemia | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Gastrointestinal necrosis | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Ileus | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Large intestine perforation | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Peritoneal haemorrhage | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Multiple organ dysfunction syndrome | General disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Catheter site haemorrhage | General disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Disease progression | General disorders | MedDRA (20.0) | Systematic Assessment |
| |
| General physical health deterioration | General disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Hyperthermia | General disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Organ failure | General disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Hepatic failure | Hepatobiliary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Acute hepatic failure | Hepatobiliary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Chronic hepatic failure | Hepatobiliary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Gallbladder disorder | Hepatobiliary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Hepatitis acute | Hepatobiliary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Hepatocellular injury | Hepatobiliary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Ischaemic hepatitis | Hepatobiliary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Endocarditis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Abscess | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Arthritis infective | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Device related sepsis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Extradural abscess | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Klebsiella sepsis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Necrotising fasciitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Peritonitis bacterial | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Anastomotic leak | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
| |
| Endotracheal intubation complication | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
| |
| Subarachnoid haemorrhage | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
| |
| Traumatic haemothorax | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
| |
| Cardiac output decreased | Investigations | MedDRA (20.0) | Systematic Assessment |
| |
| Troponin I increased | Investigations | MedDRA (20.0) | Systematic Assessment |
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| Troponin increased | Investigations | MedDRA (20.0) | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Hyperlactacidaemia | Metabolism and nutrition disorders | MedDRA (20.0) | Systematic Assessment |
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| Lactic acidosis | Metabolism and nutrition disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Fasciitis | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Lung adenocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
| |
| Lung cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
| |
| Lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
| |
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
| |
| Metastatic carcinoma of the bladder | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
| |
| Metastatic neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
| |
| Pancreatic carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
| |
| Encephalopathy | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Brain oedema | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Cerebral ischaemia | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Coma | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Vasculitis cerebral | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
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| Acute kidney injury | Renal and urinary disorders | MedDRA (20.0) | Systematic Assessment |
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| Renal failure | Renal and urinary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Mediastinal mass | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Pulmonary fibrosis | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Pulmonary haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Skin discolouration | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Peripheral ischaemia | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Shock | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
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| Shock haemorrhagic | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
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| Vasoconstriction | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Circulatory collapse | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Distributive shock | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Dry gangrene | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Extremity necrosis | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Ischaemia | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Poor peripheral circulation | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Thrombosis | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Expired product administered | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (20.0) | Systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Clinical Compliance | Ferring Pharmaceuticals | +1 833-548-1402 | DK0-Disclosure@ferring.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 20, 2017 | Sep 29, 2020 | SAP_001.pdf |
| ID | Term |
|---|---|
| D012772 | Shock, Septic |
| ID | Term |
|---|---|
| D018805 | Sepsis |
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |
Not provided
Not provided
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| OG004 | Selepressin Pooled | All selepressin arms pooled together and treated as a single arm. |
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| OG004 | Selepressin Pooled | All selepressin arms pooled together and treated as a single arm. |
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| OG004 | Selepressin Pooled | All selepressin arms pooled together and treated as a single arm. |
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| OG004 | Selepressin Pooled | All selepressin arms pooled together and treated as a single arm. |
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Starting dose: 3.5 ng/kg/min selepressin; Maximum dose: 5.25 ng/kg/min selepressin, given as an infusion. |
| OG004 | Selepressin Pooled | All selepressin arms pooled together and treated as a single arm. |
|
|
Starting dose: 3.5 ng/kg/min selepressin; Maximum dose: 5.25 ng/kg/min selepressin, given as an infusion.
| OG004 | Selepressin Pooled | All selepressin arms pooled together and treated as a single arm. |
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| Units | Counts |
|---|---|
| Participants |
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All selepressin arms pooled together and treated as a single arm. |
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| OG004 |
| Selepressin Pooled |
All selepressin arms pooled together and treated as a single arm. |
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| OG004 | Selepressin Pooled | All selepressin arms pooled together and treated as a single arm. |
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| OG004 | Selepressin Pooled | All selepressin arms pooled together and treated as a single arm. |
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| OG004 | Selepressin Pooled | All selepressin arms pooled together and treated as a single arm. |
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All selepressin arms pooled together and treated as a single arm.
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| OG004 | Selepressin Pooled | All selepressin arms pooled together and treated as a single arm. |
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| OG002 | 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. |
| OG003 | 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. |
| OG004 | Selepressin Pooled | All selepressin arms pooled together and treated as a single arm. |
|
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| OG002 |
| 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. |
| OG003 | 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. |
| OG004 | Selepressin Pooled | All selepressin arms pooled together and treated as a single arm. |
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| Yes |
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