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
Authors' conclusion
This trial did not achieve the primary outcome of improvement in SOFA score at the predefined sTREM-1 value.
Study context
- Population
- Non-COVID-19 adults (18–85 years) with septic shock and documented or suspected lung, abdominal or urinary infection, within 24 h of vasopressor initiation; 42 hospitals with intensive care units (ICUs) in seven countriesincluded in main analysis
- Participants
- 355 adults
- Comparison
- Nangibotide 0.3 or 1.0 mg/kg per h vs placebo
- Placebon = 116reference
- Low-dosen = 118
- High-dosen = 121
- Primary endpoint
- Mean difference in total SOFA score from baseline to day 5 vs placebo, in the high sTREM-1 (≥ 400 pg/mL) population and the overall modified ITT population
- Follow-up
- Day 5
Methodological detailsdouble-blind, placebo-controlled, phase 2b, multicentre, block randomisation
- Double-blind
- Placebo-controlled
- Phase 2b
- Multicentre
- Block randomisation
Primary result
As reported in the abstract
SOFA score change baseline to day 5, high sTREM-1 population
Each group vs placeboEstimate (95% CI)P value
Low-dosehigh sTREM-1 population
mean difference 0.21(−1.45 to 1.87)
P = 0.80High-dosehigh sTREM-1 population
mean difference 1.39(−0.28 to 3.06)
P = 0.104Low-doseoverall population
difference 0.20(−1.09 to 1.50)
P = 0.76High-doseoverall population
difference 1.06(−0.23 to 2.35)
P = 0.108Secondary outcomes
28-day mortality, high sTREM-1 population
28-day mortality, overall population
Sequential Organ Failure Assessment (SOFA) improvement by sTREM-1 cutoff (subgroup) · day 5
- High-dose: clinically relevant SOFA improvement (≥2 points) vs placebo with sTREM-1 ≥532 pg/mL at baseline
- Low-dose: similar pattern, lower magnitude, across all cutoffs
Safety
Treatment-emergent adverse events
Serious treatment-emergent adverse events
Treatment-emergent adverse events
- Similar between all three groups
Serious treatment-emergent adverse events
- Similar between all three groups
Original publication
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. Lancet Respir Med. Published 31 May 2023. doi:10.
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