Trial reportCritical care medicine2010
Phase 2 trial of eritoran tetrasodium (E5564), a toll-like receptor 4 antagonist, in patients with severe sepsis.
Trial report in Critical care medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 97 papers.
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
97 citing papers in PubMed, 223 citations in OpenAlex.
- Identification and characterization of a lipopolysaccharide binding, anti-inflammatory protein fromGut microbes · 2026Article
- Molecular Mechanisms of Sepsis-Associated Acute Kidney Injury.Journal of the American Society of Nephrology : JASN · 2025Review
- Unraveling immunosenescence in sepsis: from cellular mechanisms to therapeutics.Cell death & disease · 2025Review
- Review
- Massively Parallel Screening of Toll/Interleukin-1 Receptor (TIR)-Derived Peptides Reveals Multiple Toll-Like Receptors (TLRs)-Targeting Immunomodulatory Peptides.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Ferroptosis in idiopathic pulmonary fibrosis: mechanisms, impact, and therapeutic opportunities.Frontiers in immunology · 2025Review
- The Impact of Extracellular Histones and Absence of Toll-like Receptors on Cardiac Functional and Electrical Disturbances in Mouse Hearts.International journal of molecular sciences · 2024Article
- Optimal strategy for treatment of sepsis based on the host inflammatory reaction and immune response.Journal of intensive medicine · 2024Article
- Immune dysregulation in sepsis: experiences, lessons and perspectives.Cell death discovery · 2023Review
- Comparative analyses of monocyte memory dynamics from mice to humans.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- Endotoxemia in Acute Heart Failure and Cardiogenic Shock: Evidence, Mechanisms and Therapeutic Options.Journal of clinical medicine · 2023Review
- SLAMF7 regulates the inflammatory response in macrophages during polymicrobial sepsis.The Journal of clinical investigation · 2023Article
- Ginseng Sprouts Attenuate Mortality and Systemic Inflammation by Modulating TLR4/NF-κB Signaling in an LPS-Induced Mouse Model of Sepsis.International journal of molecular sciences · 2023Article
- Toll-like Receptors and Thrombopoiesis.International journal of molecular sciences · 2023Review
- Gasdermins in sepsis.Frontiers in immunology · 2023Review
- Effect of acute TLR4 inhibition on insulin resistance in humans.The Journal of clinical investigation · 2022Article
- Review of potential medical treatments for middle ear cholesteatoma.Cell communication and signaling : CCS · 2022Review
- First-in-human phase I clinical trial of a TLR4-binding DNA aptamer, ApTOLL: Safety and pharmacokinetics in healthy volunteers.Molecular therapy. Nucleic acids · 2022Article
- A Fluorescence-Polarization-Based Lipopolysaccharide-Caspase-4 Interaction Assay for the Development of Inhibitors.Molecules (Basel, Switzerland) · 2022Article
- Necrotizing enterocolitis: Bench to bedside approaches and advancing our understanding of disease pathogenesis.Frontiers in pediatrics · 2022Review
37 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issuedMultiple investigator names added.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesEndotoxin is a potent stimulus of proinflammatory response and systemic coagulation in patients with severe sepsis. Endotoxin is a component of Gram-negative bacteria that triggers an innate immune response through Toll-like receptor 4 signaling pathways in myeloid cells. We evaluated safety and tolerability of two dose regimens of eritoran tetrasodium (E5564), a synthetic Toll-like receptor 4 antagonist, and explored whether it decreases 28-day mortality rate in subjects with severe sepsis.
designProspective, randomized, double-blind, placebo-controlled, multicenter, ascending-dose phase II trial.
settingAdult intensive care units in the United States and Canada. PATIENTS: Three hundred adults within 12 hrs of recognition of severe sepsis, with Acute Physiology and Chronic Health Evaluation (APACHE) II-predicted risk of mortality between 20% and 80%.
interventionsIntravenous eritoran tetrasodium (total dose of either 45 mg or 105 mg) or placebo administered every 12 hrs for 6 days. MEASUREMENTS AND MAIN
resultsPrevalence of adverse events was similar among subjects treated with 45 mg or 105 mg of eritoran tetrasodium or with placebo. For modified intent-to-treat subjects, 28-day all-cause mortality rates were 26.6% (eritoran tetrasodium 105 mg), 32.0% (eritoran tetrasodium 45 mg), and 33.3% in the placebo group. Mortality rate in the eritoran tetrasodium 105-mg group was not significantly different from placebo (p = .335). In prespecified subgroups, subjects at highest risk of mortality by APACHE II score quartile had a trend toward lower mortality rate in the eritoran tetrasodium 105-mg group (33.3% vs. 56.3% placebo group, p = .105). A trend toward a higher mortality rate was observed in subjects in the lowest APACHE II score quartile for the eritoran 105-mg group (12.0% vs. 0.0% placebo group, p = .083).
conclusionsEritoran tetrasodium treatment appears well tolerated. The observed trend toward a lower mortality rate at the 105-mg dose, in subjects with severe sepsis and high predicted risk of mortality, should be further investigated.
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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.