Septic ShockPhase 2NCT01000649

Effects of the V1a Agonist FE 202158 in Patients With Septic Shock

A Phase 2 study testing FE 202158 1.25, FE 202158 2.5 and FE 202158 3.75 in people with Septic Shock, run by Ferring Pharmaceuticals at 16 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The purpose of this trial was to examine the safety and tolerability, pharmacokinetics of FE 202158 and to assess whether it can stabilize blood pressure and reduce vascular (blood vessel) leakage. FE 202158 had previously been tested in healthy volunteers. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Septic Shock
What is being tested?: FE 202158 1.25, FE 202158 2.5 and FE 202158 3.75
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 53 participants
Where: 16 sitesin 4 countries
Study dates: Nov 2009to Sep 2011
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Signed informed consent form by the patient or a legal representative according to local regulations
Man or woman 18 years of age or older
Proven or suspected infection
Low blood pressure
Signs of decreased circulation in the tissues
Willing to use an adequate barrier method or hormonal method of contraception, if not abstinent, from the day of informed consent to one week after the end of infusion of study medication.

Who cannot join

Present or a history (within the last 5 years) of acute coronary syndrome (myocardial infarction or unstable angina). Patients who have been asymptomatic for 6 months after coronary revascularisation are eligible.
Hypovolaemia suspected on clinical grounds, e.g. cold extremities with delayed capillary filling, low cardiac filling pressure, marked systolic or pulse pressure variation or positive leg raising test.
Known or suspected cardiac failure
Pregnancy or breastfeeding
Any cause of hypotension other than early septic shock
Use of vasopressin or terlipressin for blood pressure support during the current hospital admission

Show all 16Show fewer

Proven or suspected acute mesenteric ischemia, as judged by the investigator
Known episode of septic shock within 1 month prior to randomisation
Underlying chronic heart disease
Traumatic brain injury
Present hospitalisation with burn injury
Symptomatic peripheral vascular disease including Raynaud's syndrome
Previously randomized in this trial
Intake of an investigational drug within the last 3 months (or longer if judged by the Investigator to possibly influence the outcome of the current study)
Known participation in another clinical trial
Considered by the investigator to be unsuitable to participate in the trial for any other reason

Trial locations and contacts

16 sites in 4 countries.

Country

City, postcode or hospital

16 sites in 4 countries

United States6 sites

Cooper University Hospital
Camden, New Jersey
Division of Education and Research SMDC Health System
Duluth, Minnesota
Baylor College of Medicine
Houston, Texas
Mount Sinai School of Medicine
New York, New York
Christiana Care Health System
Newark, Delaware
Baystate Medical Center
Springfield, Massachusetts

Other trials in United States

Belgium4 sites

Clinique Universitaire St-Luc
Brussels
Erasme Hospital (Free University of Brussels)
Brussels
University Hospital Vrije Universiteit
Brussels
Service des Soins Intensits
Dinant

Other trials in Belgium

Denmark4 sites

Bispebjerg Hospital
Bispebjerg
Rigshospitalet
Copenhagen
Hillerød Hospital
Hillerød
Hvidovre Hospital
Hvidovre

Other trials in Denmark

Canada2 sites

Royal Columbian Hospital
Vancouver
St. Paul´s Hospital
Vancouver

Other trials in Canada

About this study

Official title: Infusion Proof-of-concept Trial Investigating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ascending Doses of FE 202158 in Patients With Vasodilatory Hypotension in Early Septic Shock

Read the detailed description

This was a multi-centre, double-blind, randomized, placebo-controlled, parallel group trial investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of FE 202158 (using three ascending doses) in patients with vasodilatory hypotension in early septic shock, when given as continuous infusion for up to 7 days.

The trial comprised of three treatment arms where FE 202158 was administered in 1.25 ng, 2.5 ng and 3.75 ng dose, respectively. A placebo arm was also included in the trial where patients received isotonic saline.

Efficacy of FE 202158 was determined by evaluating its ability to maintain mean arterial pressure (MAP) >60 mmHg and its modulating effect on inflammatory markers. Effects of FE 202158 on other variables like vital signs, morbidity, mortality and pulmonary function were also determined.

Conditions: Septic Shock
Being tested: FE 202158 1.25, FE 202158 2.5, FE 202158 3.75, Placebo
Keywords: V1a agonist
Medical subject headings: Shock, Septic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

FE 202158 1.25Drug
FE 202158 at dose 1.25 ng/kg/min infused.
FE 202158 2.5Drug
FE 202158 at dose 2.5 ng/kg/min infused.
FE 202158 3.75Drug
FE 202158 at dose 3.75 ng/kg/min infused.
PlaceboOther
Isotonic saline infused.

Study groups in NCT01000649
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: Drug: FE 202158 3.75
PLCBO	Placebo comparator	Patients in the arm received an intravenous infusion for up to 7 days of placebo. Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 1 up to Day 7

Secondary outcomes (23)

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.
Measured: Day 1 up to Day 7
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 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.
Measured: Day 1 up to Day 7
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 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.
Measured: Day 1 up to Day 7
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 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.
Measured: Day 1 up to Day 7
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 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.
Measured: Day 1 up to Day 7
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 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.
Measured: Day 1 up to Day 7
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 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.
Measured: Day 1 up to Day 7
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 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.
Measured: At Day 1, Day 2, Day 4, and Day 7
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 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.
Measured: At Day 1, Day 2, Day 4, and Day 7
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 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.
Measured: At Day 1, Day 2, Day 4, and Day 7
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 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.
Measured: At Day 1, Day 2, Day 4, and Day 7
Change From Baseline in Heart Rate
The change from Baseline in heart rate was analysed and presented as per the planned time points.
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.
Measured: Day 1 up to Day 7
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 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.
Measured: Day 1 up to Day 7
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 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.
Measured: Day 1 up to Day 7, Day 14 and Day 29
Pulmonary Function : Change From Baseline in PaO2/FiO2
Change from Baseline in PaO2/FiO2 was observed at each time-point.
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.
Measured: Day 1 up to Day 7
Pulmonary Function : Change From Baseline in Tidal Volume
Change from Baseline in tidal volume was observed at each time-point.
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.
Measured: Day 1 up to Day 7
Change From Baseline in Arterial Blood Gas (Lactate)
Change from Baseline in arterial blood gas (lactate) was observed at each time-point.
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.
Measured: Day 1 up to Day 7
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 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.
Measured: At Day 7
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 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.
Measured: At Day 7, Day 14 and Day 28
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 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.
Measured: At Day 7, Day 14 and Day 28
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 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.
Measured: At Day 7
Mortality
Mortality was assessed as percentage of patients dead at pre-specified time points.
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.
Measured: At Day 1, 7, 14, and 28
Incidence of Abnormal Changes in ECG
The number of patients having abnormal changes in ECG variables during the trial period was presented.
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.
Measured: Day 1 up to Day 7

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2009Sep 2011

First posted23 Oct 2009 (estimated)
Study startNov 2009
Primary completionAug 2011
Study completionSep 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Septic ShockStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 53 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01000649
Sponsor's protocol ID: FE 202158 CS02
Other IDs: EudraCT: 2009-010798-19
Status last verified: Aug 2017
First submitted: 30 Sep 2009
Last updated: 25 Sep 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 28807037
Rehberg S, Yamamoto Y, Sousse L, Bartha E, Jonkam C, Hasselbach AK, Traber LD, Cox RA, Westphal M, Enkhbaatar P, Traber DL. Selective V(1a) agonism attenuates vascular dysfunction and fluid accumulation in ovine severe sepsis. Am J Physiol Heart Circ Physiol. 2012 Nov 15;303(10):H1245-54. doi: 10.1152/ajpheart.00390.2012. Epub 2012 Sep 7.
PubMed 22961865

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 25 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Infusion Proof-of-concept Trial Investigating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ascending Doses of FE 202158 in Patients With Vasodilatory Hypotension in Early Septic Shock
ClinicalTrials.gov ID: NCT01000649
Acronym / sponsor ID: FE 202158 CS02
Conditions: Septic Shock
Keywords: V1a agonist
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 53 participants (actual)
Lead sponsor: Ferring PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Nov 2009
Primary completion: Aug 2011 (actual)
Study completion: Sep 2011 (actual)
First posted: 23 Oct 2009 (estimated)
Results: Posted 2 Jun 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 4

Arm	Type	Receives
FE 202158 1.25	Experimental	Drug: FE 202158 1.25Patients 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.
FE 202158 2.5	Experimental	Drug: FE 202158 2.5Patients 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.
FE 202158 3.75	Experimental	Drug: FE 202158 3.75Patients 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.
PLCBO	Placebo comparator	Other: PlaceboPatients in the arm received an intravenous infusion for up to 7 days of placebo.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

Signed informed consent form by the patient or a legal representative according to local regulations
Man or woman 18 years of age or older
Proven or suspected infection
Low blood pressure
Signs of decreased circulation in the tissues

Key exclusion criteria (16 listed)

Present or a history (within the last 5 years) of acute coronary syndrome (myocardial infarction or unstable angina). Patients who have been asymptomatic for 6 months after coronary revascularisation are eligible.
Hypovolaemia suspected on clinical grounds, e.g. cold extremities with delayed capillary filling, low cardiac filling pressure, marked systolic or pulse pressure variation or positive leg raising test.
Known or suspected cardiac failure
Pregnancy or breastfeeding
Any cause of hypotension other than early septic shock

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
FE 202158 1.25FE 202158 at dose 1.25 ng/kg/min infused.	Drug	FE 202158 1.25
FE 202158 2.5FE 202158 at dose 2.5 ng/kg/min infused.	Drug	FE 202158 2.5
FE 202158 3.75FE 202158 at dose 3.75 ng/kg/min infused.	Drug	FE 202158 3.75
PlaceboIsotonic saline infused.	Other	PLCBO

Primary outcome

Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine)
Time frame: Day 1 up to Day 7
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.
Proportion of Patients Maintaining Target MAP (>60) Irrespective of Open Label NE
Time frame: Day 1 up to Day 7
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.
Cumulative Dose of Open Label NE.
Time frame: Day 1 up to Day 7
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.
Infusion Rates of Open Label NE.
Time frame: Day 1 up to Day 7
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.

23 secondary outcomes

Pharmacokinetic (PK) Parameter in Patients : Steady State Concentration
Time frame: Day 1 up to Day 7
PK Parameter in Patients : Time to Steady State
Time frame: Day 1 up to Day 7
PK Parameter in Patients : Clearance
Time frame: Day 1 up to Day 7
PK Parameter in Patients : Steady State Volume of Distribution
Time frame: Day 1 up to Day 7
PK Parameter in Patients : Initial Elimination Half-life
Time frame: Day 1 up to Day 7
PK Parameter in Patients : Terminal Elimination Half-life
Time frame: Day 1 up to Day 7
Change From Baseline in C-reactive Protein (CRP)
Time frame: Day 1 up to Day 7
Change From Baseline in Tumor Necrosis Factor (TNF)-Alpha
Time frame: At Day 1, Day 2, Day 4, and Day 7
Change From Baseline in Interleukin-6 (IL-6)
Time frame: At Day 1, Day 2, Day 4, and Day 7
Change From Baseline in Interleukin-10 (IL-10)
Time frame: At Day 1, Day 2, Day 4, and Day 7
Change From Baseline in Interleukin-1 Receptor (IL-1R) Antagonist
Time frame: At Day 1, Day 2, Day 4, and Day 7
Change From Baseline in Heart Rate
Time frame: Day 1 up to Day 7
Change From Baseline in Fluid Balance
Time frame: Day 1 up to Day 7
SOFA Score
Time frame: Day 1 up to Day 7, Day 14 and Day 29
Pulmonary Function : Change From Baseline in PaO2/FiO2
Time frame: Day 1 up to Day 7
Pulmonary Function : Change From Baseline in Tidal Volume
Time frame: Day 1 up to Day 7
Change From Baseline in Arterial Blood Gas (Lactate)
Time frame: Day 1 up to Day 7
Days Alive and Free of Any Organ Dysfunction at Day 7
Time frame: At Day 7
Percentage of Patients Alive and Free of All Vasopressors
Time frame: At Day 7, Day 14 and Day 28
Percentage of Days Alive and Free of Dialysis
Time frame: At Day 7, Day 14 and Day 28
Percentage of Days Alive and Free of Ventilation
Time frame: At Day 7
Mortality
Time frame: At Day 1, 7, 14, and 28
Incidence of Abnormal Changes in ECG
Time frame: Day 1 up to Day 7

Results and safety

Results posted to the registry on 2 Jun 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
FE 202158 1.25	10	5
FE 202158 2.5	19	16
FE 202158 3.75	2	0
PLCBO	21	15

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

Time frame: Day 1 up to Day 7. Number (95% Confidence Interval). Unit: Percentage of patients

Measure	FE 202158 1.25 n = 10	FE 202158 2.5 n = 19	PLCBO n = 21
Day 1 - 12 hrs	0.0 (0.0 to 30.8)	47.1 (23.0 to 72.2)	0.0 (0.0 to 16.8)
Day 1 - 24 hrs	10.0 (0.3 to 44.5)	68.8 (41.3 to 89.0)	20.0 (5.7 to 43.7)
Day 2 - 48 hrs	55.6 (21.2 to 86.3)	66.7 (38.4 to 88.2)	38.9 (17.3 to 64.3)
Day 4 - 96 hrs	75.0 (34.9 to 96.8)	66.7 (29.9 to 92.5)	70.6 (44.0 to 89.7)
Day 7 - 168 hrs	62.5 (24.5 to 91.5)	80.0 (44.4 to 97.5)	100.0 (78.2 to 100.0)

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

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

Time frame: Day 1 up to Day 7. Number (95% Confidence Interval). Unit: Percentage of patients

Measure	FE 202158 1.25 n = 10	FE 202158 2.5 n = 19	PLCBO n = 21
Day 1 - 12 hrs	100.0 (63.1 to 100.0)	100.0 (80.5 to 100.0)	94.7 (74.0 to 99.9)
Day 1 - 24 hrs	87.5 (47.3 to 99.7)	100.0 (78.2 to 100.0)	100.0 (83.2 to 100.0)
Day 2 - 48 hrs	100.0 (66.4 to 100.0)	100.0 (76.8 to 100.0)	100.0 (81.5 to 100.0)
Day 4 - 96 hrs	100.0 (63.1 to 100.0)	100.0 (63.1 to 100.0)	100.0 (80.5 to 100.0)
Day 7 - 168 hrs	62.5 (24.5 to 91.5)	100.0 (66.4 to 100.0)	100.0 (78.2 to 100.0)

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

Primary outcome: Cumulative Dose of Open Label NE.

Time frame: Day 1 up to Day 7. Mean (Standard Deviation). Unit: µg/kg

Measure	FE 202158 1.25 n = 10	FE 202158 2.5 n = 19	PLCBO n = 21
Day 1 - 1 hour	14.3 (11.6)	13.1 (12.6)	19.2 (14.6)
Day 1 - 3 hours	40.5 (35)	30 (33.1)	57.2 (44)
Day 1 - 6 hours	75.8 (60.4)	46.9 (59.4)	110 (84)
Day 1 - 12 hours	130 (96.3)	66.5 (102)	206 (159)
Day 1 - 24 hours	211 (147)	101 (193)	360 (270)
Day 2 - 36 hours	282 (206)	122 (253)	477 (363)
Day 2 - 48 hours	349 (303)	138 (297)	554 (445)
Day 3 - 60 hours	389 (377)	150 (334)	606 (509)

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

Primary outcome: Infusion Rates of Open Label NE.

Time frame: Day 1 up to Day 7. Mean (Standard Deviation). Unit: µg/kg/min

Measure	FE 202158 1.25 n = 10	FE 202158 2.5 n = 19	PLCBO n = 21
Day 1 - 1 hour	0.24 (0.19)	0.22 (0.21)	0.32 (0.24)
Day 1 - 3 hours	0.22 (0.19)	0.11 (0.17)	0.31 (0.24)
Day 1 - 6 hours	0.18 (0.15)	0.09 (0.15)	0.28 (0.22)
Day 1 - 12 hours	0.13 (0.11)	0.06 (0.14)	0.26 (0.20)
Day 1 - 24 hours	0.09 (0.08)	0.04 (0.11)	0.19 (0.17)
Day 2 - 36 hours	0.10 (0.12)	0.02 (0.07)	0.13 (0.14)
Day 2 - 48 hours	0.08 (0.16)	0.02 (0.06)	0.08 (0.13)
Day 3 - 60 hours	0.03 (0.05)	0.02 (0.06)	0.07 (0.11)

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

23 secondary outcomes are reported in the full results.

Adverse events

Time frame: 28 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
FE 202158 1.25	2 of 10 (20%)	6 of 10 (60%)	Not reported
FE 202158 2.5	2 of 19 (10.5%)	14 of 19 (73.7%)	Not reported
FE 202158 3.75	2 of 2 (100%)	0 of 2 (0%)	Not reported
PLCBO	6 of 21 (28.6%)	13 of 21 (61.9%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 28807037Russell 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.
Derived from this study: PubMed 22961865Rehberg S, Yamamoto Y, Sousse L, Bartha E, Jonkam C, Hasselbach AK, Traber LD, Cox RA, Westphal M, Enkhbaatar P, Traber DL. Selective V(1a) agonism attenuates vascular dysfunction and fluid accumulation in ovine severe sepsis. Am J Physiol Heart Circ Physiol. 2012 Nov 15;303(10):H1245-54. doi: 10.1152/ajpheart.00390.2012. Epub 2012 Sep 7.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Clinical Development Support study director

Ferring Pharmaceuticals

16 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing FE 202158 1.25, FE 202158 2.5 and FE 202158 3.75 in people with Septic Shock, run by Ferring Pharmaceuticals at 16 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States, Belgium, Denmark, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine) (time frame: Day 1 up to Day 7). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01000649, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2017.