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
Bibliographic record
Abstract
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
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.017 | 0.006 |
| Meta-epidemiology (narrow) | 0.004 | 0.002 |
| Meta-epidemiology (broad) | 0.004 | 0.002 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.002 | 0.002 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.004 | 0.002 |
| Research integrity | 0.005 | 0.005 |
| Insufficient payload (model declined to judge) | 0.017 | 0.007 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".