Assessing the effects of fluids and antibiotics in an acute murine model of sepsis: study protocol for the National Preclinical Sepsis Platform-01 (NPSP-01) Study
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Le résumé fourni par la source
Background Sepsis remains a leading cause of mortality in critical care. Despite extensive preclinical research on sepsis pathophysiology, the development of effective therapies has been largely unsuccessful. Key obstacles include limited construct validity of animal models, insufficient methodological rigor and the lack of collaborative frameworks akin to clinical trials. These issues plague not only sepsis research, but preclinical research in general. The National Preclinical Sepsis Platform (NPSP), an interdisciplinary network under Sepsis Canada, addresses these challenges in sepsis research through multilaboratory, randomized, controlled preclinical studies. NPSP-01 will establish baseline conditions for future investigations using an acute fecal-induced peritonitis model of sepsis. Methods This randomized, controlled study will evaluate the effect of standard sepsis therapy in a mouse model of sepsis across six centres. Interlaboratory variability and the interaction of biological sex on outcomes will also be examined. C57BL/6 mice of both sexes will be randomized into sham (healthy control) + treatment, sepsis, or sepsis + treatment groups. Sepsis will be induced via intraperitoneal injection of fecal slurry, while sham mice will receive vehicle control. Antibiotics and fluids will be administered to treatment groups at 4 hours post-induction, and mice with be euthanized at 8 hours post-induction. The primary outcome is plasma interleukin-6 levels. Secondary outcomes include biological (blood gas and chemistry, white blood cell count, bacterial load), clinical (body weight, core temperature, sepsis score, mortality as measured by surrogate humane endpoints), and feasibility measures. Conclusions NPSP-01 will be the first multilaboratory study of sepsis and represents a shift in preclinical critical illness research, mirroring the rigor of clinical multicenter trials. By addressing procedural standardization, interlaboratory variability, and sex-based differences, this study aims to enhance the reliability and translational relevance of preclinical findings. The outcomes of NPSP-01 will establish foundational data for future investigations and provide a roadmap for rigorous collaborative preclinical studies to accelerate the evaluation of novel sepsis therapies. Registration PreclinicalTrials.eu PCTE0000552 Protocol Version 1.0, October 21, 2024
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Assessing the effects of fluids and antibiotics in an acute murine model of sepsis: study protocol for the National Preclinical Sepsis Platform-01 (NPSP-01) Study
- Date Crossref
- 13/02/2026
- Éditeur
- F1000 Research Ltd
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Ottawa Hospital Blueprint Translational Research Group pays non établi dans la noticeÉtablissement de santé
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University of Manitoba Department of Internal Medicine pays non établi dans la noticeUniversité ou école supérieure
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McMaster University pays non établi dans la noticeUniversité ou école supérieure
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Western University pays non établi dans la noticeUniversité ou école supérieure
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London Health Sciences Centre pays non établi dans la noticeÉtablissement de santé
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London Health Sciences Centre Research Institute pays non établi dans la noticeOrganisme public
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University of Alberta Department of Critical Care Medicine Edmonton AB Royal Alexandra Hospital pays non établi dans la noticeUniversité ou école supérieure
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University of Alberta Hospital pays non établi dans la noticeÉtablissement de santé
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Royal Alexandra Hospital pays non établi dans la noticeÉtablissement de santé
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University of Guelph Animal care services pays non établi dans la noticeUniversité ou école supérieure
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University of Calgary pays non établi dans la noticeUniversité ou école supérieure
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University of Ottawa pays non établi dans la noticeUniversité ou école supérieure
Blueprint Translational Research Group — Ottawa Hospital, Department of Internal Medicine — University of Manitoba et McMaster University, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.