Prospective evaluation of the efficacy, safety, and optimal biomarker enrichment strategy for nangibotide, a TREM-1 inhibitor, in patients with septic shock (ASTONISH): a double-blind, randomised, controlled, phase 2b trial.

François B, Lambden S, Fivez T, Gibot S, Derive M, Grouin JM, Salcedo-Magguilli M, Lemarié J, De Schryver N, Jalkanen V, Hicheur T, Garaud JJ and 13 more

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Cuvier V, Ferrer R, Bestle M, Pettilä V, Mira JP, Bouisse C, Mercier E, Vermassen J, Huberlant V, Vinatier I, Anguel N, Levy M, Laterre PF

The Lancet. Respiratory medicine31 May 2023Cited by 71 (Europe PMC)

PMID37269870DOI10.1016/s2213-2600(23)00158-3PepBankPUB-37269870

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Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study14

14 results from studies that gave the peptide. 14 results from people.

01HumanRandomized controlled trialEfficacy outcome
In septic shock patients with high sTREM-1, low-dose nangibotide did not significantly improve SOFA score versus placebo by day 5.
In plain wordsIn septic shock patients with high sTREM-1, low-dose nangibotide did not significantly improve organ function scores versus placebo.
Peptide
Nangibotide
Outcome
No significant changeSOFA score change to day 5, high sTREM-1, low dose
Study
n: not reported in source
Comparator
Placebo
Analysis
Primary
Outcome group
Intensive care and hospital outcomes · Whole body
Studied dose
0·3 mg/kg per h · intravenousAs given in this study (human).
Measurements
Mean difference in SOFA score vs placebo
0.21 SOFA points
high sTREM-1 population, low dose, baseline to day 5
95% CI of mean difference
−1.45 to 1.87 SOFA points
high sTREM-1 population, low dose, baseline to day 5
Source sentences
Summary
the mean difference in SOFA score from baseline to day 5 was 0·21 (95% CI -1·45 to 1·87, p=0·80) in the low-dose group and 1·39 (-0·28 to 3·06, p=0·104) in the high-dose group versus placebo.
2 context sentences(design, population, supporting numbers)
Summary · context
The primary outcome was the mean difference in total Sequential Organ Failure Assessment (SOFA) score from baseline to day 5 in the low-dose and high-dose groups compared with placebo, measured in the predefined high sTREM-1 (≥ 400 pg/mL) population and in the overall modified intention-to-treat population.
Summary · context
Patients were randomly assigned in a 1:1:1 ratio to intravenous nangibotide 0·3 mg/kg per h (low-dose group), nangibotide 1·0 mg/kg per h (high-dose group), or matched placebo, using a computer-generated block randomisation scheme (block size 3).
Report a problemFND-3726987001
02HumanRandomized controlled trialEfficacy outcome
In septic shock patients with high sTREM-1, high-dose nangibotide did not significantly improve SOFA score versus placebo by day 5.
In plain wordsIn septic shock patients with high sTREM-1, high-dose nangibotide did not significantly improve organ function scores versus placebo.
Peptide
Nangibotide
Outcome
No significant changeSOFA score change to day 5, high sTREM-1, high dose
Study
n: not reported in source
Comparator
Placebo
Analysis
Primary
Outcome group
Intensive care and hospital outcomes · Whole body
Studied dose
1·0 mg/kg per h · intravenousAs given in this study (human).
Measurements
Mean difference in SOFA score vs placebo
1.39 SOFA points
high sTREM-1 population, high dose, baseline to day 5
95% CI of mean difference
−0.28 to 3.06 SOFA points
high sTREM-1 population, high dose, baseline to day 5
Source sentences
Summary
the mean difference in SOFA score from baseline to day 5 was 0·21 (95% CI -1·45 to 1·87, p=0·80) in the low-dose group and 1·39 (-0·28 to 3·06, p=0·104) in the high-dose group versus placebo.
2 context sentences(design, population, supporting numbers)
Summary · context
The primary outcome was the mean difference in total Sequential Organ Failure Assessment (SOFA) score from baseline to day 5 in the low-dose and high-dose groups compared with placebo, measured in the predefined high sTREM-1 (≥ 400 pg/mL) population and in the overall modified intention-to-treat population.
Summary · context
Patients were randomly assigned in a 1:1:1 ratio to intravenous nangibotide 0·3 mg/kg per h (low-dose group), nangibotide 1·0 mg/kg per h (high-dose group), or matched placebo, using a computer-generated block randomisation scheme (block size 3).
Report a problemFND-3726987002
03HumanRandomized controlled trialEfficacy outcome
In septic shock patients overall, low-dose nangibotide did not significantly improve SOFA score versus placebo by day 5.
In plain wordsIn septic shock patients overall, low-dose nangibotide did not significantly improve organ function scores versus placebo.
Peptide
Nangibotide
Outcome
No significant changeSOFA score change to day 5, overall, low dose
Study
n: not reported in source
Comparator
Placebo
Analysis
Primary
Outcome group
Intensive care and hospital outcomes · Whole body
Studied dose
0·3 mg/kg per h · intravenousAs given in this study (human).
Measurements
Mean difference in SOFA score vs placebo
0.2 SOFA points
overall population, low dose, baseline to day 5
95% CI of mean difference
−1.09 to 1.5 SOFA points
overall population, low dose, baseline to day 5
Source sentences
Summary
In the overall population, the difference in SOFA score from baseline to day 5 between the placebo group and low-dose group was 0·20 (-1·09 to 1·50; p=0·76),and between the placebo group and the high-dose group was 1·06 (-0·23 to 2·35, p=0·108).
2 context sentences(design, population, supporting numbers)
Summary · context
The primary outcome was the mean difference in total Sequential Organ Failure Assessment (SOFA) score from baseline to day 5 in the low-dose and high-dose groups compared with placebo, measured in the predefined high sTREM-1 (≥ 400 pg/mL) population and in the overall modified intention-to-treat population.
Summary · context
Patients were randomly assigned in a 1:1:1 ratio to intravenous nangibotide 0·3 mg/kg per h (low-dose group), nangibotide 1·0 mg/kg per h (high-dose group), or matched placebo, using a computer-generated block randomisation scheme (block size 3).
Report a problemFND-3726987003
04HumanRandomized controlled trialEfficacy outcome
In septic shock patients overall, high-dose nangibotide did not significantly improve SOFA score versus placebo by day 5.
In plain wordsIn septic shock patients overall, high-dose nangibotide did not significantly improve organ function scores versus placebo.
Peptide
Nangibotide
Outcome
No significant changeSOFA score change to day 5, overall, high dose
Study
n: not reported in source
Comparator
Placebo
Analysis
Primary
Outcome group
Intensive care and hospital outcomes · Whole body
Studied dose
1·0 mg/kg per h · intravenousAs given in this study (human).
Measurements
Mean difference in SOFA score vs placebo
1.06 SOFA points
overall population, high dose, baseline to day 5
95% CI of mean difference
−0.23 to 2.35 SOFA points
overall population, high dose, baseline to day 5
Source sentences
Summary
In the overall population, the difference in SOFA score from baseline to day 5 between the placebo group and low-dose group was 0·20 (-1·09 to 1·50; p=0·76),and between the placebo group and the high-dose group was 1·06 (-0·23 to 2·35, p=0·108).
2 context sentences(design, population, supporting numbers)
Summary · context
The primary outcome was the mean difference in total Sequential Organ Failure Assessment (SOFA) score from baseline to day 5 in the low-dose and high-dose groups compared with placebo, measured in the predefined high sTREM-1 (≥ 400 pg/mL) population and in the overall modified intention-to-treat population.
Summary · context
Patients were randomly assigned in a 1:1:1 ratio to intravenous nangibotide 0·3 mg/kg per h (low-dose group), nangibotide 1·0 mg/kg per h (high-dose group), or matched placebo, using a computer-generated block randomisation scheme (block size 3).
Report a problemFND-3726987004
05HumanRandomized controlled trialSafety outcome
In septic shock patients with high sTREM-1, day 28 mortality was 39% with low-dose nangibotide versus 31% with placebo.
In plain wordsIn septic shock patients with high sTREM-1, day 28 mortality was 39% with low-dose nangibotide versus 31% with placebo.
Peptide
Nangibotide
Outcome
IncreaseDay 28 mortality, high sTREM-1, low dose
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Mortality · Whole body
Studied dose
0·3 mg/kg per h · intravenousAs given in this study (human).
Measurements
Deaths
35 patients
low dose, high sTREM-1
Mortality
39%
low dose, high sTREM-1
Deaths
23 patients
placebo, high sTREM-1
Mortality
31%
placebo, high sTREM-1
Source sentences
Summary
In the predefined high sTREM-1 cutoff population, 23 (31%) patients in the placebo group, 35 (39%) in the low-dose group, and 25 (28%) in the high-dose group had died by day 28.
2 context sentences(design, population, supporting numbers)
Summary · context
Secondary endpoints included all-cause 28-day mortality, safety, pharmacokinetics, and evaluation of the relationship between TREM-1 activation and treatment response.
Summary · context
Patients were randomly assigned in a 1:1:1 ratio to intravenous nangibotide 0·3 mg/kg per h (low-dose group), nangibotide 1·0 mg/kg per h (high-dose group), or matched placebo, using a computer-generated block randomisation scheme (block size 3).
Report a problemFND-3726987005
06HumanRandomized controlled trialSafety outcome
In septic shock patients with high sTREM-1, day 28 mortality was 28% with high-dose nangibotide versus 31% with placebo.
In plain wordsIn septic shock patients with high sTREM-1, day 28 mortality was 28% with high-dose nangibotide versus 31% with placebo.
Peptide
Nangibotide
Outcome
DecreaseDay 28 mortality, high sTREM-1, high dose
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Mortality · Whole body
Studied dose
1·0 mg/kg per h · intravenousAs given in this study (human).
Measurements
Deaths
25 patients
high dose, high sTREM-1
Mortality
28%
high dose, high sTREM-1
Deaths
23 patients
placebo, high sTREM-1
Mortality
31%
placebo, high sTREM-1
Source sentences
Summary
In the predefined high sTREM-1 cutoff population, 23 (31%) patients in the placebo group, 35 (39%) in the low-dose group, and 25 (28%) in the high-dose group had died by day 28.
2 context sentences(design, population, supporting numbers)
Summary · context
Secondary endpoints included all-cause 28-day mortality, safety, pharmacokinetics, and evaluation of the relationship between TREM-1 activation and treatment response.
Summary · context
Patients were randomly assigned in a 1:1:1 ratio to intravenous nangibotide 0·3 mg/kg per h (low-dose group), nangibotide 1·0 mg/kg per h (high-dose group), or matched placebo, using a computer-generated block randomisation scheme (block size 3).
Report a problemFND-3726987006
07HumanRandomized controlled trialSafety outcome
In septic shock patients overall, day 28 mortality was 32% with low-dose nangibotide versus 25% with placebo.
In plain wordsIn septic shock patients overall, day 28 mortality was 32% with low-dose nangibotide versus 25% with placebo.
Peptide
Nangibotide
Outcome
IncreaseDay 28 mortality, overall, low dose
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Mortality · Whole body
Studied dose
0·3 mg/kg per h · intravenousAs given in this study (human).
Measurements
Deaths
38 patients
low dose, overall
Mortality
32%
low dose, overall
Deaths
29 patients
placebo, overall
Mortality
25%
placebo, overall
Source sentences
Summary
In the overall population, 29 (25%) patients in the placebo, 38 (32%) in the low-dose, and 30 (25%) in the high-dose group had died by day 28.
2 context sentences(design, population, supporting numbers)
Summary · context
Secondary endpoints included all-cause 28-day mortality, safety, pharmacokinetics, and evaluation of the relationship between TREM-1 activation and treatment response.
Summary · context
Patients were randomly assigned in a 1:1:1 ratio to intravenous nangibotide 0·3 mg/kg per h (low-dose group), nangibotide 1·0 mg/kg per h (high-dose group), or matched placebo, using a computer-generated block randomisation scheme (block size 3).
Report a problemFND-3726987007
08HumanRandomized controlled trialSafety outcome
In septic shock patients overall, day 28 mortality was 25% with both high-dose nangibotide and placebo.
In plain wordsIn septic shock patients overall, day 28 mortality was 25% with both high-dose nangibotide and placebo.
Peptide
Nangibotide
Outcome
Not applicableDay 28 mortality, overall, high dose
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Mortality · Whole body
Studied dose
1·0 mg/kg per h · intravenousAs given in this study (human).
Measurements
Deaths
30 patients
high dose, overall
Mortality
25%
high dose, overall
Deaths
29 patients
placebo, overall
Mortality
25%
placebo, overall
Source sentences
Summary
In the overall population, 29 (25%) patients in the placebo, 38 (32%) in the low-dose, and 30 (25%) in the high-dose group had died by day 28.
2 context sentences(design, population, supporting numbers)
Summary · context
Secondary endpoints included all-cause 28-day mortality, safety, pharmacokinetics, and evaluation of the relationship between TREM-1 activation and treatment response.
Summary · context
Patients were randomly assigned in a 1:1:1 ratio to intravenous nangibotide 0·3 mg/kg per h (low-dose group), nangibotide 1·0 mg/kg per h (high-dose group), or matched placebo, using a computer-generated block randomisation scheme (block size 3).
Report a problemFND-3726987008
09HumanRandomized controlled trialSafety outcome
In septic shock patients, treatment-emergent adverse events were similar with low-dose nangibotide and placebo, affecting 96% in each arm.
In plain wordsIn septic shock patients, adverse events were similar with low-dose nangibotide and placebo, affecting 96% in each arm.
Peptide
Nangibotide
Outcome
No significant changeTreatment-emergent adverse events, low dose
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Adverse events · Whole body
Studied dose
0·3 mg/kg per h · intravenousAs given in this study (human).
Measurements
Patients with treatment-emergent adverse events
113 patients
low dose
Patients with treatment-emergent adverse events
96%
low dose
Patients with treatment-emergent adverse events
111 patients
placebo
Patients with treatment-emergent adverse events
96%
placebo
Source sentences
Summary
The number of treatment-emergent adverse events (111 [96%] patients in the placebo group, 113 [96%] in the low-dose group, and 115 [95%] in the high-dose group) and serious treatment-emergent adverse events (28 [24%], 26 [22%], and 31 [26%]) was similar between all three groups.
2 context sentences(design, population, supporting numbers)
Summary · context
Secondary endpoints included all-cause 28-day mortality, safety, pharmacokinetics, and evaluation of the relationship between TREM-1 activation and treatment response.
Summary · context
Patients were randomly assigned in a 1:1:1 ratio to intravenous nangibotide 0·3 mg/kg per h (low-dose group), nangibotide 1·0 mg/kg per h (high-dose group), or matched placebo, using a computer-generated block randomisation scheme (block size 3).
Report a problemFND-3726987009
10HumanRandomized controlled trialSafety outcome
In septic shock patients, treatment-emergent adverse events were similar with high-dose nangibotide and placebo, affecting 95% versus 96%.
In plain wordsIn septic shock patients, adverse events were similar with high-dose nangibotide and placebo, affecting 95% versus 96%.
Peptide
Nangibotide
Outcome
No significant changeTreatment-emergent adverse events, high dose
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Adverse events · Whole body
Studied dose
1·0 mg/kg per h · intravenousAs given in this study (human).
Measurements
Patients with treatment-emergent adverse events
115 patients
high dose
Patients with treatment-emergent adverse events
95%
high dose
Patients with treatment-emergent adverse events
111 patients
placebo
Patients with treatment-emergent adverse events
96%
placebo
Source sentences
Summary
The number of treatment-emergent adverse events (111 [96%] patients in the placebo group, 113 [96%] in the low-dose group, and 115 [95%] in the high-dose group) and serious treatment-emergent adverse events (28 [24%], 26 [22%], and 31 [26%]) was similar between all three groups.
2 context sentences(design, population, supporting numbers)
Summary · context
Secondary endpoints included all-cause 28-day mortality, safety, pharmacokinetics, and evaluation of the relationship between TREM-1 activation and treatment response.
Summary · context
Patients were randomly assigned in a 1:1:1 ratio to intravenous nangibotide 0·3 mg/kg per h (low-dose group), nangibotide 1·0 mg/kg per h (high-dose group), or matched placebo, using a computer-generated block randomisation scheme (block size 3).
Report a problemFND-3726987010
11HumanRandomized controlled trialSafety outcome
In septic shock patients, serious treatment-emergent adverse events were similar with low-dose nangibotide and placebo, affecting 22% versus 24%.
In plain wordsIn septic shock patients, serious adverse events were similar with low-dose nangibotide and placebo, affecting 22% versus 24%.
Peptide
Nangibotide
Outcome
No significant changeSerious treatment-emergent adverse events, low dose
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Adverse events · Whole body
Studied dose
0·3 mg/kg per h · intravenousAs given in this study (human).
Measurements
Patients with serious treatment-emergent adverse events
26 patients
low dose
Patients with serious treatment-emergent adverse events
22%
low dose
Patients with serious treatment-emergent adverse events
28 patients
placebo
Patients with serious treatment-emergent adverse events
24%
placebo
Source sentences
Summary
The number of treatment-emergent adverse events (111 [96%] patients in the placebo group, 113 [96%] in the low-dose group, and 115 [95%] in the high-dose group) and serious treatment-emergent adverse events (28 [24%], 26 [22%], and 31 [26%]) was similar between all three groups.
2 context sentences(design, population, supporting numbers)
Summary · context
Secondary endpoints included all-cause 28-day mortality, safety, pharmacokinetics, and evaluation of the relationship between TREM-1 activation and treatment response.
Summary · context
Patients were randomly assigned in a 1:1:1 ratio to intravenous nangibotide 0·3 mg/kg per h (low-dose group), nangibotide 1·0 mg/kg per h (high-dose group), or matched placebo, using a computer-generated block randomisation scheme (block size 3).
Report a problemFND-3726987011
12HumanRandomized controlled trialSafety outcome
In septic shock patients, serious treatment-emergent adverse events were similar with high-dose nangibotide and placebo, affecting 26% versus 24%.
In plain wordsIn septic shock patients, serious adverse events were similar with high-dose nangibotide and placebo, affecting 26% versus 24%.
Peptide
Nangibotide
Outcome
No significant changeSerious treatment-emergent adverse events, high dose
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Adverse events · Whole body
Studied dose
1·0 mg/kg per h · intravenousAs given in this study (human).
Measurements
Patients with serious treatment-emergent adverse events
31 patients
high dose
Patients with serious treatment-emergent adverse events
26%
high dose
Patients with serious treatment-emergent adverse events
28 patients
placebo
Patients with serious treatment-emergent adverse events
24%
placebo
Source sentences
Summary
The number of treatment-emergent adverse events (111 [96%] patients in the placebo group, 113 [96%] in the low-dose group, and 115 [95%] in the high-dose group) and serious treatment-emergent adverse events (28 [24%], 26 [22%], and 31 [26%]) was similar between all three groups.
2 context sentences(design, population, supporting numbers)
Summary · context
Secondary endpoints included all-cause 28-day mortality, safety, pharmacokinetics, and evaluation of the relationship between TREM-1 activation and treatment response.
Summary · context
Patients were randomly assigned in a 1:1:1 ratio to intravenous nangibotide 0·3 mg/kg per h (low-dose group), nangibotide 1·0 mg/kg per h (high-dose group), or matched placebo, using a computer-generated block randomisation scheme (block size 3).
Report a problemFND-3726987012
13HumanRandomized controlled trialEfficacy outcome
In septic shock patients with baseline sTREM-1 ≥532 pg/mL, high-dose nangibotide improved SOFA score by at least two points over placebo.
In plain wordsIn septic shock patients with baseline sTREM-1 ≥532 pg/mL, high-dose nangibotide improved organ function scores more than placebo by day 5.
Peptide
Nangibotide
Outcome
IncreaseSOFA improvement at higher sTREM-1 cutoff, high dose
Study
n: not reported in source
Comparator
Placebo
Outcome group
Intensive care and hospital outcomes · Whole body
Studied dose
1·0 mg/kg per h · intravenousAs given in this study (human).
Source sentences
Summary
High-dose nangibotide led to a clinically relevant improvement in SOFA score (of two points or more) from baseline to day 5 over placebo in those with higher cutoff concentrations (≥532 pg/mL) of sTREM-1 at baseline.
1 context sentence(design, population, supporting numbers)
Summary · context
Patients were randomly assigned in a 1:1:1 ratio to intravenous nangibotide 0·3 mg/kg per h (low-dose group), nangibotide 1·0 mg/kg per h (high-dose group), or matched placebo, using a computer-generated block randomisation scheme (block size 3).
Report a problemFND-3726987013
14HumanRandomized controlled trialEfficacy outcome
In septic shock patients, low-dose nangibotide showed a similar SOFA response pattern versus placebo across cutoffs, with smaller effects than high dose.
In plain wordsIn septic shock patients, low-dose nangibotide showed smaller organ function benefits than high dose across biomarker cutoffs, relative to placebo.
Peptide
Nangibotide
Outcome
IncreaseSOFA response across sTREM-1 cutoffs, low dose
Study
n: not reported in source
Comparator
Placebo
Outcome group
Intensive care and hospital outcomes · Whole body
Studied dose
0·3 mg/kg per h · intravenousAs given in this study (human).
Source sentences
Summary
Low dose nangibotide displayed a similar pattern with lower magnitude of effect across all cutoff values.
2 context sentences(design, population, supporting numbers)
Summary · context
High-dose nangibotide led to a clinically relevant improvement in SOFA score (of two points or more) from baseline to day 5 over placebo in those with higher cutoff concentrations (≥532 pg/mL) of sTREM-1 at baseline.
Summary · context
Patients were randomly assigned in a 1:1:1 ratio to intravenous nangibotide 0·3 mg/kg per h (low-dose group), nangibotide 1·0 mg/kg per h (high-dose group), or matched placebo, using a computer-generated block randomisation scheme (block size 3).
Report a problemFND-3726987014

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 ongoing · source ClinicalTrials.gov (opens in a new tab)

Active, not recruitingPhase 2NCT04055909

Efficacy, Safety and Tolerability of Nangibotide in Patients With Septic Shock

Inotremn = 35513 Nov 2019 to est. 9 May 2023

Shock, Septic

Trial page ClinicalTrials.govUpdated 11 Apr 2023

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

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

Subjects

Terms as the source lists them.

Publication types

MeSH terms

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