Effects of the V1a Agonist FE 202158 in Patients With Sep... | NCT01000649

ID	Type	Description	Link
EudraCT: 2009-010798-19

Label	Type	Description	Intervention Names
FE 202158 1.25	Experimental	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.	Drug: FE 202158 1.25
FE 202158 2.5	Experimental	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.	Drug: FE 202158 2.5
FE 202158 3.75	Experimental	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 3.75 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.	Drug: FE 202158 3.75
PLCBO	Placebo Comparator	Patients in the arm received an intravenous infusion for up to 7 days of placebo.	Other: Placebo

Name	Type	Description	Arm Group Labels	Other Names
FE 202158 1.25	Drug	FE 202158 at dose 1.25 ng/kg/min infused.	FE 202158 1.25

Measure	Description	Time Frame
Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine)	Data were evaluated for target MAP of ≥ 60 mmHg. A 95% confidence interval (CI) was calculated and presented using Clopper-Pearson method. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.	Day 1 up to Day 7
Proportion of Patients Maintaining Target MAP (>60) Irrespective of Open Label NE	Data were evaluated for target MAP of ≥ 60 mmHg. A 95% confidence interval (CI) was calculated and presented using Clopper-Pearson method. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.	Day 1 up to Day 7
Cumulative Dose of Open Label NE.	Cumulative Dose of Open Label NE over 7 days. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.	Day 1 up to Day 7
Infusion Rates of Open Label NE.	Mean open label NE infusion rate within each predefined time period. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.	Day 1 up to Day 7

Measure	Description	Time Frame
Pharmacokinetic (PK) Parameter in Patients : Steady State Concentration	PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

Name	Affiliation	Role
Clinical Development Support	Ferring Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Christiana Care Health System		Newark	Delaware		United States
Baystate Medical Center

PubMed Identifier	Type	Citation	Retractions
28807037	Result	Russell JA, Vincent JL, Kjolbye AL, Olsson H, Blemings A, Spapen H, Carl P, Laterre PF, Grundemar L. Selepressin, a novel selective vasopressin V1A agonist, is an effective substitute for norepinephrine in a phase IIa randomized, placebo-controlled trial in septic shock patients. Crit Care. 2017 Aug 15;21(1):213. doi: 10.1186/s13054-017-1798-7.
22961865

ID	Title	Description
FG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
FG001

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

Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine)

Data were evaluated for target MAP of ≥ 60 mmHg. A 95% confidence interval (CI) was calculated and presented using Clopper-Pearson method.

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

The analysis population consist of Full Analysis Set, which comprised of all patients who were dosed.

Posted

Number

95% Confidence Interval

Percentage of patients

Day 1 up to Day 7

ID	Title	Description
OG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG002	PLCBO	Patients in the arm received an intravenous infusion for up to 7 days of placebo.

Units	Counts
Participants	OG00010 OG00119 OG00221

Title

Denominators

Categories

Day 1 - 12 hrs

Title	Measurements
	OG0000.0(0.0 to 30.8) OG00147.1(23.0 to 72.2) OG0020.0(0.0 to 16.8)

Day 1 - 24 hrs

Primary

Proportion of Patients Maintaining Target MAP (>60) Irrespective of Open Label NE

Data were evaluated for target MAP of ≥ 60 mmHg. A 95% confidence interval (CI) was calculated and presented using Clopper-Pearson method.

The analysis population consist of Full Analysis Set, which comprised of all patients who were dosed.

Posted

Number

95% Confidence Interval

Percentage of patients

Day 1 up to Day 7

ID	Title	Description
OG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG002	PLCBO

Primary

Cumulative Dose of Open Label NE.

Cumulative Dose of Open Label NE over 7 days.

The analysis population consist of Full Analysis Set, which comprised of all patients who were dosed.

Posted

Mean

Standard Deviation

µg/kg

Day 1 up to Day 7

ID	Title	Description
OG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG002	PLCBO	Patients in the arm received an intravenous infusion for up to 7 days of placebo.

Secondary

Pharmacokinetic (PK) Parameter in Patients : Steady State Concentration

PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution.

The analysis population consist of FAS, which comprised of all patients who were dosed.

Posted

Mean

Standard Deviation

ng/mL

Day 1 up to Day 7

ID	Title	Description
OG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.

Units	Counts

Secondary

PK Parameter in Patients : Time to Steady State

PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution.

The analysis population consist of FAS, which comprised of all patients who were dosed.

Posted

Mean

Standard Deviation

Hour

Day 1 up to Day 7

ID	Title	Description
OG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.

Units	Counts

Secondary

PK Parameter in Patients : Clearance

PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution.

The analysis population consist of FAS, which comprised of all patients who were dosed.

Posted

Mean

Standard Deviation

Litre/hour

Day 1 up to Day 7

ID	Title	Description
OG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.

Units	Counts

Secondary

PK Parameter in Patients : Steady State Volume of Distribution

PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution.

The analysis population consist of FAS, which comprised of all patients who were dosed.

Posted

Mean

Standard Deviation

Litre

Day 1 up to Day 7

ID	Title	Description
OG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.

Units	Counts

Secondary

PK Parameter in Patients : Initial Elimination Half-life

PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution.

The analysis population consist of FAS, which comprised of all patients who were dosed.

Posted

Mean

Standard Deviation

Hour

Day 1 up to Day 7

ID	Title	Description
OG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.

Units	Counts

Secondary

PK Parameter in Patients : Terminal Elimination Half-life

PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution.

The analysis population consist of FAS, which comprised of all patients who were dosed.

Posted

Mean

Standard Deviation

Hour

Day 1 up to Day 7

ID	Title	Description
OG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.

Units	Counts

Secondary

Change From Baseline in C-reactive Protein (CRP)

The change from Baseline in CRP levels were analysed and presented as per the planned time points.

The analysis population consist of FAS, which comprised of all patients who were dosed.

Posted

Mean

Standard Deviation

mg/L

Day 1 up to Day 7

ID	Title	Description
OG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG002	PLCBO	Patients in the arm received an intravenous infusion for up to 7 days of placebo.

Secondary

Change From Baseline in Tumor Necrosis Factor (TNF)-Alpha

The change from Baseline in TNF-alpha levels were analysed and presented as per the planned time points.

The analysis population consist of FAS, which comprised of all patients who were dosed.

Posted

Mean

Standard Deviation

ng/L

At Day 1, Day 2, Day 4, and Day 7

ID	Title	Description
OG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG002	PLCBO	Patients in the arm received an intravenous infusion for up to 7 days of placebo.

Secondary

Change From Baseline in Interleukin-6 (IL-6)

The change from Baseline in IL-6 levels were analysed and presented as per the planned time points.

The analysis population consist of FAS, which comprised of all patients who were dosed.

Posted

Mean

Standard Deviation

ng/L

At Day 1, Day 2, Day 4, and Day 7

ID	Title	Description
OG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG002	PLCBO	Patients in the arm received an intravenous infusion for up to 7 days of placebo.

Secondary

Change From Baseline in Interleukin-10 (IL-10)

The change from Baseline in IL-10 levels were analysed and presented as per the planned time points.

The analysis population consist of FAS, which comprised of all patients who were dosed.

Posted

Mean

Standard Deviation

ng/L

At Day 1, Day 2, Day 4, and Day 7

ID	Title	Description
OG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG002	PLCBO	Patients in the arm received an intravenous infusion for up to 7 days of placebo.

Primary

Infusion Rates of Open Label NE.

Mean open label NE infusion rate within each predefined time period.

The analysis population consist of FAS, which comprised of all patients who were dosed.

Posted

Mean

Standard Deviation

µg/kg/min

Day 1 up to Day 7

ID	Title	Description
OG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG002	PLCBO	Patients in the arm received an intravenous infusion for up to 7 days of placebo.

Secondary

Change From Baseline in Interleukin-1 Receptor (IL-1R) Antagonist

The change from Baseline in IL-1R levels were analysed and presented as per the planned time points.

The analysis population consist of FAS, which comprised of all patients who were dosed.

Posted

Mean

Standard Deviation

µg/L

At Day 1, Day 2, Day 4, and Day 7

ID	Title	Description
OG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG002	PLCBO	Patients in the arm received an intravenous infusion for up to 7 days of placebo.

Secondary

Change From Baseline in Heart Rate

The change from Baseline in heart rate was analysed and presented as per the planned time points.

The analysis population consist of Safety Analysis Set, which comprised of all patients who were dosed.

Posted

Mean

Standard Deviation

Beats per minute

Day 1 up to Day 7

ID	Title	Description
OG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG002	PLCBO	Patients in the arm received an intravenous infusion for up to 7 days of placebo.

Secondary

Change From Baseline in Fluid Balance

The change from Baseline in fluid balance were analysed and presented as per the planned time points. The fluid balance was adjusted for length of time interval and weight.

The analysis population consist of FAS, which comprised of all patients who were dosed.

Posted

Mean

Standard Deviation

mL/hour/kg

Day 1 up to Day 7

ID	Title	Description
OG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG002	PLCBO	Patients in the arm received an intravenous infusion for up to 7 days of placebo.

Secondary

SOFA Score

The SOFA score, is used to track a patient's status during the stay in an intensive care unit. This scoring system is used to determine the extent of a person's organ function or rate of failure. The scoring system comprise of scores for six different system: Respiratory System; Nervous System; Cardiovascular System; Liver; Coagulation; and Renal System. Score for each system ranges from 0-4 (0=normal, 4=worst).

Total SOFA score is a sum of the individual system score and range from 0 to 24, 0 being the better and 24 being the worst patient status.

The analysis population consist of FAS, which comprised of all patients who were dosed.

Posted

Mean

Standard Deviation

Score on a scale

Day 1 up to Day 7, Day 14 and Day 29

ID	Title	Description
OG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.

Secondary

Pulmonary Function : Change From Baseline in PaO2/FiO2

Change from Baseline in PaO2/FiO2 was observed at each time-point.

The analysis population consist of Safety Analysis Set, which comprised of all patients who were dosed.

Posted

Mean

Standard Deviation

Ratio

Day 1 up to Day 7

ID	Title	Description
OG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG002	PLCBO	Patients in the arm received an intravenous infusion for up to 7 days of placebo.

Secondary

Pulmonary Function : Change From Baseline in Tidal Volume

Change from Baseline in tidal volume was observed at each time-point.

The analysis population consist of Safety Analysis Set, which comprised of all patients who were dosed.

Posted

Mean

Standard Deviation

mL/kg

Day 1 up to Day 7

ID	Title	Description
OG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG002	PLCBO	Patients in the arm received an intravenous infusion for up to 7 days of placebo.

Secondary

Change From Baseline in Arterial Blood Gas (Lactate)

Change from Baseline in arterial blood gas (lactate) was observed at each time-point.

The analysis population consist of Safety Analysis Set, which comprised of all patients who were dosed.

Posted

Mean

Standard Deviation

mmol/L

Day 1 up to Day 7

ID	Title	Description
OG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG002	PLCBO	Patients in the arm received an intravenous infusion for up to 7 days of placebo.

Secondary

Days Alive and Free of Any Organ Dysfunction at Day 7

Percentage of days alive and free of any organ dysfunction (i.e. no. of days divided by 7).

The analysis population consist of FAS, which comprised of all patients who were dosed.

Posted

Mean

Standard Deviation

Percentage of days

At Day 7

ID	Title	Description
OG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG002	PLCBO	Patients in the arm received an intravenous infusion for up to 7 days of placebo.

Secondary

Percentage of Patients Alive and Free of All Vasopressors

Percentage of patients alive and free of all vasopressors was assessed on Days 7, 14, and 28.

The analysis population consist of FAS, which comprised of all patients who were dosed.

Posted

Number

Percentage of patients

At Day 7, Day 14 and Day 28

ID	Title	Description
OG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG002	PLCBO	Patients in the arm received an intravenous infusion for up to 7 days of placebo.

Secondary

Percentage of Days Alive and Free of Dialysis

Percentage of days alive and free of dialysis was assessed on Days 7, 14, and 28.

The analysis population consist of FAS, which comprised of all patients who were dosed.

Posted

Mean

Standard Deviation

Percentage of days

At Day 7, Day 14 and Day 28

ID	Title	Description
OG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG002	PLCBO	Patients in the arm received an intravenous infusion for up to 7 days of placebo.

Secondary

Percentage of Days Alive and Free of Ventilation

Percentage of days alive and free of ventilation was assessed on Days 7, 14, and 28.

The analysis population consist of FAS, which comprised of all patients who were dosed.

Posted

Mean

Standard Deviation

Percentage of days

At Day 7

ID	Title	Description
OG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG002	PLCBO	Patients in the arm received an intravenous infusion for up to 7 days of placebo.

Secondary

Mortality

Mortality was assessed as percentage of patients dead at pre-specified time points.

The analysis population consist of FAS, which comprised of all patients who were dosed.

Posted

Number

Percentage of patients

At Day 1, 7, 14, and 28

ID	Title	Description
OG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG002	PLCBO	Patients in the arm received an intravenous infusion for up to 7 days of placebo.

Secondary

Incidence of Abnormal Changes in ECG

The number of patients having abnormal changes in ECG variables during the trial period was presented.

The analysis population consist of Safety Analysis Set, which comprised of all patients who were dosed.

Posted

Number

Number of patients

Day 1 up to Day 7

ID	Title	Description
OG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
OG002	PLCBO	Patients in the arm received an intravenous infusion for up to 7 days of placebo.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0013 events3 affected19 at risk EG0020 events0 affected2 at risk EG0037 events7 affected21 at risk
Coagulopathy	Blood and lymphatic system disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA 12.1	Systematic Assessment	EG0002 events1 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 12.1	Systematic Assessment	EG0001 events1 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0014 events3 affected19 at risk EG0020 events0 affected2 at risk EG003
Bradycardia	Cardiac disorders	MedDRA 12.1	Systematic Assessment	EG0001 events1 affected10 at risk EG0013 events2 affected19 at risk EG0020 events0 affected2 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA 12.1	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Cardiac valve vegetation	Cardiac disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Cyanosis	Cardiac disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA 12.1	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Supraventricular extrasystoles	Cardiac disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Tachycardia	Cardiac disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0012 events2 affected19 at risk EG0020 events0 affected2 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Impaired gastric emptying	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0012 events2 affected19 at risk EG0020 events0 affected2 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Gastric haemorrhage	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Haematemesis	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Generalised oedema	General disorders	MedDRA 12.1	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Chest pain	General disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Hypothermia	General disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Hepatic failure	Hepatobiliary disorders	MedDRA 12.1	Systematic Assessment	EG0002 events2 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Abdominal abscess	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Catheter related infection	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Enterobacter infection	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Genital herpes	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Pneumonia herpes viral	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Stenotrophomonas infection	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Urinary tract infection enterococcal	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Wound infection	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Post procedural complication	Injury, poisoning and procedural complications	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Gastrointestinal stoma complication	Injury, poisoning and procedural complications	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Mechanical ventilation complication	Injury, poisoning and procedural complications	MedDRA 12.1	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Hepatic enzyme increased	Investigations	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Platelet count decreased	Investigations	MedDRA 12.1	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Troponin increased	Investigations	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Blood phosphorus	Investigations	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Blood phosphorus decreased	Investigations	MedDRA 12.1	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Blood phosphorus increased	Investigations	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Blood potassium increased	Investigations	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Candida serology positive	Investigations	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Haemoglobin decreased	Investigations	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Oxygen saturation decreased	Investigations	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 12.1	Systematic Assessment	EG0001 events1 affected10 at risk EG0012 events2 affected19 at risk EG0020 events0 affected2 at risk EG003
Metabolic acidosis	Metabolism and nutrition disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Fluid retention	Metabolism and nutrition disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Hyperlactacidaemia	Metabolism and nutrition disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 12.1	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Hypovolaemia	Metabolism and nutrition disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Metabolic alkalosis	Metabolism and nutrition disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Vitamin K deficiency	Metabolism and nutrition disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Dysarthria	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Lethargy	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Tremor	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 12.1	Systematic Assessment	EG0001 events1 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Agitation	Psychiatric disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Delirium	Psychiatric disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Hallucinations	Psychiatric disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Restlessness	Psychiatric disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Oliguria	Renal and urinary disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Renal failure acute	Renal and urinary disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Urinary bladder haemorrhage	Renal and urinary disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Scrotal oedema	Reproductive system and breast disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Respiratory depression	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Decubitus ulcer	Skin and subcutaneous tissue disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Hyperkeratosis	Skin and subcutaneous tissue disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Rash macular	Skin and subcutaneous tissue disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Scar pain	Skin and subcutaneous tissue disorders	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Abdominal cavity drainage	Surgical and medical procedures	MedDRA 12.1	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003
Hypertension	Vascular disorders	MedDRA 12.1	Systematic Assessment	EG0001 events1 affected10 at risk EG0015 events4 affected19 at risk EG0020 events0 affected2 at risk EG003
Hypotension	Vascular disorders	MedDRA 12.1	Systematic Assessment	EG0001 events1 affected10 at risk EG0012 events1 affected19 at risk EG0020 events0 affected2 at risk EG003
Vena cava thrombosis	Vascular disorders	MedDRA 12.1	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected19 at risk EG0020 events0 affected2 at risk EG003

ID	Term
D018805	Sepsis
D007239	Infections
D018746	Systemic Inflammatory Response Syndrome
D007249	Inflammation
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D012769	Shock

ID	Title	Description
BG000	FE 202158 1.25	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
BG001	FE 202158 2.5	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
BG002	FE 202158 3.75	Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 3.75 ng/kg/min. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
BG003	PLCBO	Patients in the arm received an intravenous infusion for up to 7 days of placebo.
BG004	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	FE 202158 1.25	Patients in the arm received a continuous intravenous infusion of FE 202158 1.25 ng/kg/min up to seven consecutive days. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.	2	10	6	10
EG001	FE 202158 2.5	Patients in the arm received a continuous intravenous infusion of FE 202158 2.5 ng/kg/min up to seven consecutive days. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.	2	19	14	19
EG002	FE 202158 3.75	Patients in the arm received a continuous intravenous infusion of FE 202158 3.75 ng/kg/min up to seven consecutive days. FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.	2	2	0	2
EG003	PLCBO	Patients in the arm received a continuous intravenous infusion of isotonic saline up to seven consecutive days.	6	21	13	21