Selepressin, a novel selective vasopressin V_1A agonist, is an effective substitute for norepinephrine in a phase IIa randomized, placebo-controlled trial in septic shock patients.

Russell JA, Vincent JL, Kjølbye AL, Olsson H, Blemings A, Spapen H, Carl P, Laterre PF, Grundemar L

Critical care (London, England)15 Aug 2017Cited by 77 (Europe PMC)

PMID28807037PMCIDPMC5557574DOI10.1186/s13054-017-1798-7PepBankPUB-28807037

Summary

BackgroundVasopressin is widely used for vasopressor support in septic shock patients, but experimental evidence suggests that selective V_1A agonists are superior. The initial pharmacodynamic effects, pharmacokinetics, and safety of selepressin, a novel V_1A-selective vasopressin analogue, was examined in a phase IIa trial in septic shock patients.MethodsThis was a randomized, double-blind, placebo-controlled multicenter trial in 53 patients in early septic shock (aged ≥18 years, fluid resuscitation, requiring vasopressor support) who received selepressin 1.25 ng/kg/minute (n = 10), 2.5 ng/kg/minute (n = 19), 3.75 ng/kg/minute (n = 2), or placebo (n = 21) until shock resolution or a maximum of 7 days. If mean arterial pressure (MAP) ≥65 mmHg was not maintained, open-label norepinephrine was added. Co-primary endpoints were maintenance of MAP >60 mmHg without norepinephrine, norepinephrine dose, and proportion of patients maintaining MAP >60 mmHg with or without norepinephrine over 7 days. Secondary endpoints included cumulative fluid balance, organ dysfunction, pharmacokinetics, and safety.ResultsA higher proportion of the patients receiving 2.5 ng/kg/minute selepressin maintained MAP >60 mmHg without norepinephrine (about 50% and 70% at 12 and 24 h, respectively) vs. 1.25 ng/kg/minute selepressin and placebo (p < 0.01). The 7-day cumulative doses of norepinephrine were 761, 659, and 249 μg/kg (placebo 1.25 ng/kg/minute and 2.5 ng/kg/minute, respectively; 2.5 ng/kg/minute vs. placebo; p < 0.01). Norepinephrine infusion was weaned more rapidly in selepressin 2.5 ng/kg/minute vs. placebo (0.04 vs. 0.18 μg/kg/minute at 24 h, p < 0.001), successfully maintaining target MAP and reducing norepinephrine dose vs. placebo (first 24 h, p < 0.001). Cumulative net fluid balance was lower from day 5 onward in the selepressin 2.5 ng/kg/minute group vs. placebo (p < 0.05). The selepressin 2.5 ng/kg/minute group had a greater proportion of days alive and free of ventilation vs. placebo (p < 0.02). Selepressin (2.5 ng/kg/minute) was well tolerated, with a similar frequency of treatment-emergent adverse events for selepressin 2.5 ng/kg/minute and placebo. Two patients were infused at 3.75 ng/kg/minute, one of whom had the study drug infusion discontinued for possible safety reasons, with subsequent discontinuation of this dose group.ConclusionsIn septic shock patients, selepressin 2.5 ng/kg/minute was able to rapidly replace norepinephrine while maintaining adequate MAP, and it may improve fluid balance and shorten the time of mechanical ventilation.Trial registrationClinicalTrials.gov, NCT01000649 . Registered on September 30, 2009.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study9

9 results from studies that gave the peptide. 9 results from people.

01HumanRandomized controlled trialEfficacy outcome
In septic shock, more patients maintained MAP above 60 mmHg without norepinephrine with selepressin 2.5 ng/kg/minute than placebo.
In plain wordsIn septic shock, selepressin 2.5 ng/kg/minute maintained target blood pressure without norepinephrine in more patients than placebo.
Peptide
Selepressin
Outcome
IncreaseMAP maintenance without norepinephrine versus placebo
Study
n = 40
Comparator
Placebo
Analysis
Primary
Outcome group
Blood pressure · Cardiovascular
Studied dose
2.5 ng/kg/minute · infusion · Until shock resolution or a maximum of 7 daysAs given in this study (human).
Measurements
Patients maintaining MAP >60 mmHg without norepinephrine
≈ 50%
selepressin 2.5 ng/kg/minute at 12 h
Patients maintaining MAP >60 mmHg without norepinephrine
≈ 70%
selepressin 2.5 ng/kg/minute at 24 h
Source sentences
Summary
A higher proportion of the patients receiving 2.5 ng/kg/minute selepressin maintained MAP >60 mmHg without norepinephrine (about 50% and 70% at 12 and 24 h, respectively) vs. 1.25 ng/kg/minute selepressin and placebo (p < 0.01).
2 context sentences(design, population, supporting numbers)
Summary · context
This was a randomized, double-blind, placebo-controlled multicenter trial in 53 patients in early septic shock (aged ≥18 years, fluid resuscitation, requiring vasopressor support)
Summary · context
If mean arterial pressure (MAP) ≥65 mmHg was not maintained, open-label norepinephrine was added.
Show in the study text Report a problemFND-2880703701
02HumanRandomized controlled trialEfficacy outcome
In septic shock, cumulative norepinephrine was 249 μg/kg with selepressin 2.5 ng/kg/minute versus 761 μg/kg with placebo over 7 days.
In plain wordsIn septic shock, selepressin 2.5 ng/kg/minute reduced cumulative norepinephrine use compared with placebo.
Peptide
Selepressin
Outcome
DecreaseCumulative norepinephrine dose at higher dose
Study
n = 40
Comparator
Placebo
Analysis
Primary
Outcome group
Blood pressure · Cardiovascular
Studied dose
2.5 ng/kg/minute · infusion · Until shock resolution or a maximum of 7 daysAs given in this study (human).
Measurements
7-day cumulative norepinephrine dose
249 μg/kg
selepressin 2.5 ng/kg/minute
7-day cumulative norepinephrine dose
761 μg/kg
placebo
Source sentences
Summary
The 7-day cumulative doses of norepinephrine were 761, 659, and 249 μg/kg (placebo 1.25 ng/kg/minute and 2.5 ng/kg/minute, respectively; 2.5 ng/kg/minute vs. placebo; p < 0.01).
2 context sentences(design, population, supporting numbers)
Summary · context
This was a randomized, double-blind, placebo-controlled multicenter trial in 53 patients in early septic shock (aged ≥18 years, fluid resuscitation, requiring vasopressor support)
Summary · context
If mean arterial pressure (MAP) ≥65 mmHg was not maintained, open-label norepinephrine was added.
Show in the study text Report a problemFND-2880703703
03HumanRandomized controlled trialEfficacy outcome
In septic shock, cumulative norepinephrine was 659 μg/kg with selepressin 1.25 ng/kg/minute versus 761 μg/kg with placebo over 7 days.
In plain wordsIn septic shock, cumulative norepinephrine was 659 μg/kg with selepressin 1.25 ng/kg/minute versus 761 μg/kg with placebo.
Peptide
Selepressin
Outcome
Direction not reportedCumulative norepinephrine dose at lower dose
Study
n = 31
Comparator
Placebo
Analysis
Primary
Outcome group
Blood pressure · Cardiovascular
Studied dose
1.25 ng/kg/minute · infusion · Until shock resolution or a maximum of 7 daysAs given in this study (human).
Measurements
7-day cumulative norepinephrine dose
659 μg/kg
selepressin 1.25 ng/kg/minute
7-day cumulative norepinephrine dose
761 μg/kg
placebo
Source sentences
Summary
The 7-day cumulative doses of norepinephrine were 761, 659, and 249 μg/kg (placebo 1.25 ng/kg/minute and 2.5 ng/kg/minute, respectively; 2.5 ng/kg/minute vs. placebo; p < 0.01).
2 context sentences(design, population, supporting numbers)
Summary · context
This was a randomized, double-blind, placebo-controlled multicenter trial in 53 patients in early septic shock (aged ≥18 years, fluid resuscitation, requiring vasopressor support)
Summary · context
If mean arterial pressure (MAP) ≥65 mmHg was not maintained, open-label norepinephrine was added.
Show in the study text Report a problemFND-2880703704
04HumanRandomized controlled trialEfficacy outcome
In septic shock, more patients maintained MAP above 60 mmHg without norepinephrine with selepressin 2.5 than 1.25 ng/kg/minute.
In plain wordsIn septic shock, selepressin 2.5 ng/kg/minute maintained target blood pressure without norepinephrine in more patients than selepressin 1.25 ng/kg/minute.
Peptide
Selepressin
Outcome
IncreaseMAP maintenance without norepinephrine versus lower dose
Study
n = 29
Comparator
Selepressin 1.25 ng/kg/minute
Analysis
Primary
Outcome group
Blood pressure · Cardiovascular
Studied dose
2.5 ng/kg/minute · infusion · Until shock resolution or a maximum of 7 daysAs given in this study (human).
Measurements
Patients maintaining MAP >60 mmHg without norepinephrine
≈ 50%
selepressin 2.5 ng/kg/minute at 12 h
Patients maintaining MAP >60 mmHg without norepinephrine
≈ 70%
selepressin 2.5 ng/kg/minute at 24 h
Source sentences
Summary
A higher proportion of the patients receiving 2.5 ng/kg/minute selepressin maintained MAP >60 mmHg without norepinephrine (about 50% and 70% at 12 and 24 h, respectively) vs. 1.25 ng/kg/minute selepressin and placebo (p < 0.01).
2 context sentences(design, population, supporting numbers)
Summary · context
This was a randomized, double-blind, placebo-controlled multicenter trial in 53 patients in early septic shock (aged ≥18 years, fluid resuscitation, requiring vasopressor support)
Summary · context
If mean arterial pressure (MAP) ≥65 mmHg was not maintained, open-label norepinephrine was added.
Show in the study text Report a problemFND-2880703702
05HumanRandomized controlled trialEfficacy outcome
In septic shock, cumulative net fluid balance was lower from day 5 onward with selepressin than placebo.
In plain wordsIn septic shock, fluid accumulation was lower from day 5 onward with selepressin 2.5 ng/kg/minute than placebo.
Peptide
Selepressin
Outcome
DecreaseCumulative net fluid balance
Study
n = 40
Comparator
Placebo
Analysis
Secondary
Outcome group
Electrolyte balance · Whole body
Studied dose
2.5 ng/kg/minute · infusion · Until shock resolution or a maximum of 7 daysAs given in this study (human).
Source sentences
Summary
Cumulative net fluid balance was lower from day 5 onward in the selepressin 2.5 ng/kg/minute group vs. placebo (p < 0.05).
2 context sentences(design, population, supporting numbers)
Summary · context
This was a randomized, double-blind, placebo-controlled multicenter trial in 53 patients in early septic shock (aged ≥18 years, fluid resuscitation, requiring vasopressor support)
Summary · context
If mean arterial pressure (MAP) ≥65 mmHg was not maintained, open-label norepinephrine was added.
Show in the study text Report a problemFND-2880703707
06HumanRandomized controlled trialSafety outcome
In septic shock, treatment-emergent adverse event frequency was similar with selepressin 2.5 ng/kg/minute and placebo.
In plain wordsIn septic shock, adverse event frequency was similar with selepressin 2.5 ng/kg/minute and placebo.
Peptide
Selepressin
Outcome
No significant changeTreatment-emergent adverse events
Study
n = 40
Comparator
Placebo
Analysis
Secondary
Outcome group
Adverse events · Whole body
Studied dose
2.5 ng/kg/minute · infusion · Until shock resolution or a maximum of 7 daysAs given in this study (human).
Source sentences
Summary
Selepressin (2.5 ng/kg/minute) was well tolerated, with a similar frequency of treatment-emergent adverse events for selepressin 2.5 ng/kg/minute and placebo.
2 context sentences(design, population, supporting numbers)
Summary · context
This was a randomized, double-blind, placebo-controlled multicenter trial in 53 patients in early septic shock (aged ≥18 years, fluid resuscitation, requiring vasopressor support)
Summary · context
If mean arterial pressure (MAP) ≥65 mmHg was not maintained, open-label norepinephrine was added.
Show in the study text Report a problemFND-2880703709
07HumanRandomized controlled trialSafety outcome
In septic shock, one of two patients receiving selepressin 3.75 ng/kg/minute discontinued infusion for possible safety reasons, ending this dose group.
In plain wordsIn septic shock, one of two patients receiving selepressin 3.75 ng/kg/minute stopped infusion for possible safety reasons.
Peptide
Selepressin
Outcome
Not applicableInfusion discontinuation for possible safety reasons
Study
n = 2
Analysis
Secondary
Outcome group
Adverse events · Whole body
Studied dose
3.75 ng/kg/minute · infusion · Until shock resolution or a maximum of 7 daysAs given in this study (human).
Source sentences
Summary
Two patients were infused at 3.75 ng/kg/minute, one of whom had the study drug infusion discontinued for possible safety reasons, with subsequent discontinuation of this dose group.
2 context sentences(design, population, supporting numbers)
Summary · context
This was a randomized, double-blind, placebo-controlled multicenter trial in 53 patients in early septic shock (aged ≥18 years, fluid resuscitation, requiring vasopressor support)
Summary · context
If mean arterial pressure (MAP) ≥65 mmHg was not maintained, open-label norepinephrine was added.
Show in the study text Report a problemFND-2880703710
08HumanRandomized controlled trialEfficacy outcome
In septic shock, norepinephrine infusion declined faster with selepressin than placebo, reaching 0.04 versus 0.18 μg/kg/minute at 24 h.
In plain wordsIn septic shock, norepinephrine infusion decreased faster with selepressin 2.5 ng/kg/minute than with placebo.
Peptide
Selepressin
Outcome
DecreaseNorepinephrine infusion reduction
Study
n = 40
Comparator
Placebo
Outcome group
Blood pressure · Cardiovascular
Studied dose
2.5 ng/kg/minute · infusion · Until shock resolution or a maximum of 7 daysAs given in this study (human).
Measurements
Norepinephrine infusion rate at 24 h
0.04 μg/kg/minute
selepressin 2.5 ng/kg/minute
Norepinephrine infusion rate at 24 h
0.18 μg/kg/minute
placebo
Source sentences
Summary
Norepinephrine infusion was weaned more rapidly in selepressin 2.5 ng/kg/minute vs. placebo (0.04 vs. 0.18 μg/kg/minute at 24 h, p < 0.001), successfully maintaining target MAP and reducing norepinephrine dose vs. placebo (first 24 h, p < 0.001).
2 context sentences(design, population, supporting numbers)
Summary · context
This was a randomized, double-blind, placebo-controlled multicenter trial in 53 patients in early septic shock (aged ≥18 years, fluid resuscitation, requiring vasopressor support)
Summary · context
If mean arterial pressure (MAP) ≥65 mmHg was not maintained, open-label norepinephrine was added.
Show in the study text Report a problemFND-2880703705
09HumanRandomized controlled trialEfficacy outcome
In septic shock, selepressin increased the proportion of days alive and free of ventilation versus placebo.
In plain wordsIn septic shock, selepressin 2.5 ng/kg/minute increased the proportion of days alive without ventilation compared with placebo.
Peptide
Selepressin
Outcome
IncreaseDays alive and free of ventilation
Study
n = 40
Comparator
Placebo
Outcome group
Respiratory function · Respiratory
Studied dose
2.5 ng/kg/minute · infusion · Until shock resolution or a maximum of 7 daysAs given in this study (human).
Source sentences
Summary
The selepressin 2.5 ng/kg/minute group had a greater proportion of days alive and free of ventilation vs. placebo (p < 0.02).
2 context sentences(design, population, supporting numbers)
Summary · context
This was a randomized, double-blind, placebo-controlled multicenter trial in 53 patients in early septic shock (aged ≥18 years, fluid resuscitation, requiring vasopressor support)
Summary · context
If mean arterial pressure (MAP) ≥65 mmHg was not maintained, open-label norepinephrine was added.
Show in the study text Report a problemFND-2880703708

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 2Results postedNCT01000649

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

Ferring Pharmaceuticalsn = 53Nov 2009 to Sept 2011

Septic Shock

Trial page ClinicalTrials.govUpdated 25 Sept 2017

Version history

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Version 2Current
27 Oct 2026, 18:20 UTC
Study results updated
Version 1
27 Oct 2026, 16:32 UTC
First added · source update from Europe PMC

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