Trial reportCritical care (London, England)2022
Baseline plasma IL-18 may predict simvastatin treatment response in patients with ARDS: a secondary analysis of the HARP-2 randomised clinical trial.
Trial report in Critical care (London, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.
What it found
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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
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 36 citations in OpenAlex.
- Genome-wide association study of susceptibility to acute respiratory distress syndrome.EBioMedicine · 2025Pooled it
- Pooled it
- Evaluation of Plasma Biomarkers to Understand the Biology and Heterogeneity of Treatment Effect in Lower Tidal Volume Ventilation Facilitated by Extracorporeal CO2 Removal in Acute Hypoxemic Respiratory Failure: A Secondary Analysis of the REST Trial.Critical care explorations · 2025Trial
- Effect of total cholesterol and statin therapy on mortality in ARDS patients: a secondary analysis of the SAILS and HARP-2 trials.Critical care (London, England) · 2023Trial
- 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
- Article
- The NLRP3 inflammasome in physiological and dysfunctional host response in human sepsis and critical illness: a narrative review.Critical care (London, England) · 2026Review
- Tetracycline-loaded nanomotors target neutrophil activation and oxidative stress in acute lung injury.iScience · 2026Article
- Optimizing endpoints in early phase clinical trials of acute respiratory distress syndrome.American journal of respiratory and critical care medicine · 2026Article
- The landscape of protein post-translational modifications in the pathogenesis of acute respiratory distress syndrome.Journal of thoracic disease · 2026Review
- Cytokine-based strategies to improve prognostic enrichment of pediatric ARDS.Critical care (London, England) · 2026Observational
- The potential role of CD44+ monocytes in mediating hyperinflammatory response in bronchopulmonary dysplasia in very premature infants.Pediatric research · 2026Article
- Immunometabolic control of macrophage plasticity in wound healing: mechanistic insights and therapeutic opportunities.Frontiers in immunology · 2026Review
- One syndrome, many diseases: toward precision pharmacotherapy in acute respiratory distress syndrome.Frontiers in pharmacology · 2026Review
- Immunobiological effects of tocilizumab across respiratory subphenotypes in COVID-19 ARDS.Intensive care medicine experimental · 2025Article
- Effects of simvastatin pretreatment on platelet activation and hypercoagulable state in septic mice.European journal of medical research · 2025Article
- Sepsis subphenotypes, theragnostics and personalized sepsis care.Intensive care medicine · 2025Review
- Clinical management of sepsis-associated acute respiratory distress syndrome: current evidence and future directions.Frontiers in medicine · 2025Review
- The role of the interplay between macrophage glycolytic reprogramming and NLRP3 inflammasome activation in acute lung injury/acute respiratory distress syndrome.Clinical and translational medicine · 2024Review
- Towards personalized medicine: a scoping review of immunotherapy in sepsis.Critical care (London, England) · 2024Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundInterleukin (IL)-18 is a marker of inflammasome activation, and high baseline plasma IL-18 is associated with increased mortality in patients with sepsis-induced ARDS. The aim of this analysis was to determine if simvastatin was associated with benefit in patients with ARDS and high plasma IL-18.
methodsIn this secondary analysis of the HARP-2 study, we compared 28-day mortality and response to simvastatin according to baseline plasma IL-18 using cox proportional hazards analysis. Separately, monocyte-derived macrophages from healthy volunteers were pre-incubated with simvastatin or rosuvastatin before stimulation with ATP and LPS, and the effect on secreted IL-18 and IL-1β compared.
results511 patients from HARP-2 had available data. High baseline plasma IL-18 (≥ 800 pg/ml) was associated with increased 28-day mortality (high IL-18 30.6% vs. low IL-18 17.5%; HR 1.89 [95% CI 1.30-2.73]; p = 0.001). Allocation to simvastatin in patients with high baseline plasma IL-18 was associated with a lower probability of 28-day mortality compared with placebo (24.0% vs 36.8%; p = 0.01). Finally, simvastatin, but not rosuvastatin, reduced stimulated macrophage secretion of IL-18 and IL-1β.
conclusionIn patients with high baseline plasma IL-18, simvastatin is associated with a higher probability of survival, and this effect may be due to reduced inflammasome activation. These data suggest that baseline plasma IL-18 may allow a personalised treatment approach by identifying patients with ARDS who could benefit from simvastatin therapy.
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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.