Trial reportCritical care medicine2018
Mortality Benefit of Recombinant Human Interleukin-1 Receptor Antagonist for Sepsis Varies by Initial Interleukin-1 Receptor Antagonist Plasma Concentration.
Trial report in Critical care medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A consensus immune dysregulation framework for sepsis and critical illnesses.Nature medicine · 2025Guideline
- [Pharmacological immunomodulation in sepsis].Medizinische Klinik, Intensivmedizin und Notfallmedizin · 2026Review
- Cytokine-based strategies to improve prognostic enrichment of pediatric ARDS.Critical care (London, England) · 2026Observational
- Host-directed immune therapies: a second front in the battle against sepsis.The Journal of clinical investigation · 2026Review
- Immunology of Sepsis.Clinics in chest medicine · 2026Review
- Hyper-inflammation and immunosuppression: redefining sepsis therapy using modern approaches.Frontiers in pharmacology · 2026Review
- Effect of anakinra on cytokine storm during sepsis-induced multiple organ dysfunction syndrome: case report and preclinical investigation.Frontiers in immunology · 2026Article
- Genetic associations in sepsis and ARDS.Frontiers in pharmacology · 2026Review
- The immunology of sepsis: translating new insights into clinical practice.Nature reviews. Nephrology · 2026Review
- Potential of biomarker-based enrichment strategies to identify critically ill patients for emerging cell death interventions.Cell death and differentiation · 2025Article
- The Interleukin Network in Sepsis: From Cytokine Storm to Clinical Applications.Diagnostics (Basel, Switzerland) · 2025Review
- Review
- Identifying a unique signature of sepsis in patients with pre-existing cirrhosis.Critical care (London, England) · 2025Article
- Unraveling immunosenescence in sepsis: from cellular mechanisms to therapeutics.Cell death & disease · 2025Review
- Enhancing Patient Selection in Sepsis Clinical Trials Design Through an AI Enrichment Strategy: Algorithm Development and Validation.Journal of medical Internet research · 2024Article
- Clinical phenotypes of sepsis: a narrative review.Journal of thoracic disease · 2024Review
- Navigating the Modern Landscape of Sepsis: Advances in Diagnosis and Treatment.International journal of molecular sciences · 2024Review
- Towards personalized medicine: a scoping review of immunotherapy in sepsis.Critical care (London, England) · 2024Article
- Highly secreted tryptophanyl tRNA synthetase 1 as a potential theranostic target for hypercytokinemic severe sepsis.EMBO molecular medicine · 2024Article
- Subphenotypes of Acute Respiratory Distress Syndrome: Advancing Towards Precision Medicine.Tuberculosis and respiratory diseases · 2024Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
objectivePlasma interleukin-1 beta may influence sepsis mortality, yet recombinant human interleukin-1 receptor antagonist did not reduce mortality in randomized trials. We tested for heterogeneity in the treatment effect of recombinant human interleukin-1 receptor antagonist by baseline plasma interleukin-1 beta or interleukin-1 receptor antagonist concentration.
designRetrospective subgroup analysis of randomized controlled trial.
settingMulticenter North American and European clinical trial. PATIENTS: Five hundred twenty-nine subjects with sepsis and hypotension or hypoperfusion, representing 59% of the original trial population.
interventionsRandom assignment of placebo or recombinant human interleukin-1 receptor antagonist × 72 hours. MEASUREMENTS AND MAIN
resultsWe measured prerandomization plasma interleukin-1 beta and interleukin-1 receptor antagonist and tested for statistical interaction between recombinant human interleukin-1 receptor antagonist treatment and baseline plasma interleukin-1 receptor antagonist or interleukin-1 beta concentration on 28-day mortality. There was significant heterogeneity in the effect of recombinant human interleukin-1 receptor antagonist treatment by plasma interleukin-1 receptor antagonist concentration whether plasma interleukin-1 receptor antagonist was divided into deciles (interaction p = 0.046) or dichotomized (interaction p = 0.028). Interaction remained present across different predicted mortality levels. Among subjects with baseline plasma interleukin-1 receptor antagonist above 2,071 pg/mL (n = 283), recombinant human interleukin-1 receptor antagonist therapy reduced adjusted mortality from 45.4% to 34.3% (adjusted risk difference, -0.12; 95% CI, -0.23 to -0.01), p = 0.044. Mortality in subjects with plasma interleukin-1 receptor antagonist below 2,071 pg/mL was not reduced by recombinant human interleukin-1 receptor antagonist (adjusted risk difference, +0.07; 95% CI, -0.04 to +0.17), p = 0.230. Interaction between plasma interleukin-1 beta concentration and recombinant human interleukin-1 receptor antagonist treatment was not statistically significant.
conclusionsWe report a heterogeneous effect of recombinant human interleukin-1 receptor antagonist on 28-day sepsis mortality that is potentially predictable by plasma interleukin-1 receptor antagonist in one trial. A precision clinical trial of recombinant human interleukin-1 receptor antagonist targeted to septic patients with high plasma interleukin-1 receptor antagonist may be worthy of consideration.
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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.