Trial reportAmerican journal of respiratory and critical care medicine2019
Transcriptomic Signatures in Sepsis and a Differential Response to Steroids. From the VANISH Randomized Trial.
Trial report in American journal of respiratory and critical care medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04280497 (A Multicentre Concealed-Allocation Multi-arms Blinded Randomized Controlled Trial to Identify the Best Sepsis Population for Corticotherapy), which is not on this map. Cited by 207 papers, 6 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Multicentre Concealed-Allocation Multi-arms Blinded Randomized Controlled Trial to Identify the Best Sepsis Population for Corticotherapy
Who cites it
207 citing papers in PubMed, 6 syntheses or guidelines pooled it.
- Systematic review and meta-analysis of humoral immunity proteins and mortality in sepsis.Critical care (London, England) · 2025Pooled it
- A consensus immune dysregulation framework for sepsis and critical illnesses.Nature medicine · 2025Guideline
- A consensus blood transcriptomic framework for sepsis.Nature medicine · 2025Guideline
- Predictive enrichment using biomarkers in studies of critically-ill patients with sepsis: a systematic review.Critical care (London, England) · 2025Pooled it
- Corticosteroids for treating sepsis in children and adults.The Cochrane database of systematic reviews · 2025Pooled it
- The Diagnostic Utility of Host RNA Biosignatures in Adult Patients With Sepsis: A Systematic Review and Meta-Analysis.Critical care explorations · 2025Pooled it
- Longitudinal multiomic signatures of ARDS and sepsis inflammatory phenotypes identify pathways associated with mortality.The Journal of clinical investigation · 2026Trial
- Heterogeneity in the Effect of Early Goal-Directed Therapy for Septic Shock: A Secondary Analysis of Two Multicenter International Trials.Critical care medicine · 2025Trial
- Clustering identifies endotypes of traumatic brain injury in an intensive care cohort: a CENTER-TBI study.Critical care (London, England) · 2022Trial
- The relationship between adrenocortical candidate gene expression and clinical response to hydrocortisone in patients with septic shock.Intensive care medicine · 2021Trial
- A neutrophil subset defined by intracellular olfactomedin 4 is associated with mortality in sepsis.American journal of physiology. Lung cellular and molecular physiology · 2021Trial
- Monocyte Trajectories Endotypes Are Associated With Worsening in Septic Patients.Frontiers in immunology · 2021Trial
- Nangibotide in patients with septic shock: a Phase 2a randomized controlled clinical trial.Intensive care medicine · 2020Trial
- From early recognition to precision medicine: advances in the diagnosis and management of adult sepsis and septic shock-a narrative review.Infection · 2026Review
- Hemodynamic trajectory phenotypes may modify associations between corticosteroid timing and outcomes in septic shock.Journal of clinical monitoring and computing · 2026Article
- Evaluating plasma ferritin and suPAR as treatable traits for critically ill patients with COVID-19 treated with anakinra: an exploratory analysis of the immune modulation domain of the REMAP-CAP randomised clinical trial.Critical care (London, England) · 2026Observational
- Deciphering sepsis molecular subtypes using large-scale data to identify subtype-specific drug repurposing.bioRxiv : the preprint server for biology · 2026Article
- Recent advances in screening, diagnosis, prognosis and personalized treatment of sepsis.European journal of microbiology & immunology · 2026Review
- Systems Bioengineering of Septic Shock Metabolism: Citrulline, β-Hydroxybutyrate and Plasma Biomarker-Based Phenotyping.Biomolecules · 2026Review
- Reconsidering the use of predicted body weight when setting tidal volumes in female patients.Intensive care medicine · 2026Article
147 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
9 authors.
Funding
Abstract
rationaleThere remains uncertainty about the role of corticosteroids in sepsis with clear beneficial effects on shock duration, but conflicting survival effects. Two transcriptomic sepsis response signatures (SRSs) have been identified. SRS1 is relatively immunosuppressed, whereas SRS2 is relatively immunocompetent.
objectivesWe aimed to categorize patients based on SRS endotypes to determine if these profiles influenced response to either norepinephrine or vasopressin, or to corticosteroids in septic shock.
methodsA post hoc analysis was performed of a double-blind, randomized clinical trial in septic shock (VANISH [Vasopressin vs. Norepinephrine as Initial Therapy in Septic Shock]). Patients were included within 6 hours of onset of shock and were randomized to receive norepinephrine or vasopressin followed by hydrocortisone or placebo. Genome-wide gene expression profiling was performed and SRS endotype was determined by a previously established model using seven discriminant genes. MEASUREMENTS AND MAIN
resultsSamples were available from 176 patients: 83 SRS1 and 93 SRS2. There was no significant interaction between SRS group and vasopressor assignment (P = 0.50). However, there was an interaction between assignment to hydrocortisone or placebo, and SRS endotype (P = 0.02). Hydrocortisone use was associated with increased mortality in those with an SRS2 phenotype (odds ratio = 7.9; 95% confidence interval = 1.6-39.9).
conclusionsTranscriptomic profile at onset of septic shock was associated with response to corticosteroids. Those with the immunocompetent SRS2 endotype had significantly higher mortality when given corticosteroids compared with placebo. Clinical trial registered with www.clinicaltrials.gov (ISRCTN 20769191).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.