Cited by 810Sepsis Diagnosis and TreatmentInflammation biomarkers and pathwaysVitamin C and Antioxidants Research

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Why have clinical trials in sepsis failed?

Marshall, John C.·2014·Trends in Molecular Medicine

DOI 10.1016/j.molmed.2014.01.007

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Abstract

The systemic inflammatory response is biologically complex, redundant, and activated by both infectious and noninfectious triggers. Its manipulation can cause both benefit and harm. More than 100 randomized clinical trials have tested the hypothesis that modulating the septic response to infection can improve survival. With one short-lived exception, none of these has resulted in new treatments. The current challenge for sepsis research lies in a failure of concept and reluctance to abandon a demonstrably ineffectual research model. Future success will necessitate large studies of clinical and biochemical epidemiology to understand the course of illness, better integration of basic and clinical science, and the creation of stratification systems to target treatment towards those who are most likely to benefit.

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Crossref · 10.1016/j.molmed.2014.01.007

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Additional file 7 of Propofol improves survival in a murine model of sepsis via inhibiting Rab5a-mediated intracellular trafficking of TLR4
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Additional file 9 of Integrated PERSEVERE and endothelial biomarker risk model predicts death and persistent MODS in pediatric septic shock: a secondary analysis of a prospective observational study
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Additional file 4 of Integrated PERSEVERE and endothelial biomarker risk model predicts death and persistent MODS in pediatric septic shock: a secondary analysis of a prospective observational study
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Additional file 2 of Targeted plasma proteomics reveals signatures discriminating COVID-19 from sepsis with pneumonia
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Additional file 8 of Integrated PERSEVERE and endothelial biomarker risk model predicts death and persistent MODS in pediatric septic shock: a secondary analysis of a prospective observational study
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Additional file 3 of Propofol improves survival in a murine model of sepsis via inhibiting Rab5a-mediated intracellular trafficking of TLR4
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Additional file 2 of Propofol improves survival in a murine model of sepsis via inhibiting Rab5a-mediated intracellular trafficking of TLR4
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Additional file 5 of Integrated PERSEVERE and endothelial biomarker risk model predicts death and persistent MODS in pediatric septic shock: a secondary analysis of a prospective observational study
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Additional file 6 of Integrated PERSEVERE and endothelial biomarker risk model predicts death and persistent MODS in pediatric septic shock: a secondary analysis of a prospective observational study
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Additional file 3 of Integrated PERSEVERE and endothelial biomarker risk model predicts death and persistent MODS in pediatric septic shock: a secondary analysis of a prospective observational study
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Additional file 10 of Integrated PERSEVERE and endothelial biomarker risk model predicts death and persistent MODS in pediatric septic shock: a secondary analysis of a prospective observational study
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Additional file 2 of Integrated PERSEVERE and endothelial biomarker risk model predicts death and persistent MODS in pediatric septic shock: a secondary analysis of a prospective observational study
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Additional file 1 of Exploring the biomarkers and potential therapeutic drugs for sepsis via integrated bioinformatic analysis
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Additional file 7 of Integrated PERSEVERE and endothelial biomarker risk model predicts death and persistent MODS in pediatric septic shock: a secondary analysis of a prospective observational study
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Additional file 4 of Propofol improves survival in a murine model of sepsis via inhibiting Rab5a-mediated intracellular trafficking of TLR4
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Additional file 3 of Exploring the biomarkers and potential therapeutic drugs for sepsis via integrated bioinformatic analysis
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Additional file 2 of Vitamin C for ≥ 5 days is associated with decreased hospital mortality in sepsis subgroups: a nationwide cohort study
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Additional file 1 of Propofol improves survival in a murine model of sepsis via inhibiting Rab5a-mediated intracellular trafficking of TLR4
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Additional file 2 of Exploring the biomarkers and potential therapeutic drugs for sepsis via integrated bioinformatic analysis
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Additional file 5 of Propofol improves survival in a murine model of sepsis via inhibiting Rab5a-mediated intracellular trafficking of TLR4
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Additional file 3 of Vitamin C for ≥ 5 days is associated with decreased hospital mortality in sepsis subgroups: a nationwide cohort study
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Authors: Marshall, J. C.
Affiliations: St. Michael's Hospital (CA)
Corresponding author: Marshall, John C.
ORCID: Marshall, John C.
Venue: Trends in Molecular Medicine
Publisher: Elsevier BV
Published: 2014-04
Volume: 20
Issue: 4
Pages: 195-203
ISSN: 1471-4914 (ISSN-L)
DOI: 10.1016/j.molmed.2014.01.007
OpenAlex: W1991209345
Cited by: 805
References: 56
Citations by year: 2026: 77 · 2025: 75 · 2024: 69 · 2023: 75 · 2022: 96 · 2021: 66 · 2020: 72 · 2019: 69 · 2018: 59 · 2017: 62 · 2016: 45 · 2015: 28 · 2014: 12
FWCI: 6.58
Type: journal article
Language: en
Open access: closed
Locations: Trends in Molecular Medicine (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
Keywords: sepsis, clinical trial failure, systemic inflammatory response, sepsis treatment, translational research, patient stratification, sepsis epidemiology, inflammatory markers
MeSH terms: Animals, Clinical Trials as Topic, Drug Evaluation, Preclinical, Humans, Immunity, Innate, Immunologic Factors, Treatment Outcome, Sepsis

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