Trial reportCritical care medicine2025
Heterogeneity in the Effect of Early Goal-Directed Therapy for Septic Shock: A Secondary Analysis of Two Multicenter International Trials.
Trial report in Critical care medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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
10 citing papers in PubMed.
- Relationship Between Phenotyping and Individualized Absolute Risk Differences in Sepsis: A Secondary Analysis of Two Approaches in Two Multicenter Trials.Critical care explorations · 2025Trial
- What place for pragmatic RCTs in intensive care?Critical care (London, England) · 2026Review
- Effect of norepinephrine initiation timing on mortality in septic shock: a multicenter cohort study.BMC anesthesiology · 2026Observational
- Septic shock in the era of precision medicine: rethinking fluids, vasopressors, and immunomodulation.Frontiers in medicine · 2026Review
- Prognostic Value of the Charlson Comorbidity Index for Mortality and Machine Learning-Based Prediction in Critically Ill Patients with Paralytic Ileus: Retrospective Cohort Study.JMIR medical informatics · 2025Article
- Finding the Four-Leaf CLOVERS: Biologic Subphenotypes and Fluid Tolerance in Sepsis.American journal of respiratory and critical care medicine · 2025Article
- A systematic methodological evaluation of sepsis guidelines: Protocol for quality assessment and consistency of recommendations.Acta anaesthesiologica Scandinavica · 2025Article
- FEDERATED LEARNING OF ROBUST INDIVIDUALIZED DECISION RULES WITH APPLICATION TO HETEROGENEOUS MULTIHOSPITAL SEPSIS POPULATION.The annals of applied statistics · 2025Article
- Evidence-based personalised medicine in critical care: a framework for quantifying and applying individualised treatment effects in patients who are critically ill.The Lancet. Respiratory medicine · 2025Review
- Key Concepts in Machine Learning and Clinical Applications in the Cardiac Intensive Care Unit.Current cardiology reports · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors.
Funding
Abstract
objectivesThe optimal approach for resuscitation in septic shock remains unclear despite multiple randomized controlled trials (RCTs). Our objective was to investigate whether previously uncharacterized variation across individuals in their response to resuscitation strategies may contribute to conflicting average treatment effects in prior RCTs.
designWe randomly split study sites from the Australian Resuscitation of Sepsis Evaluation (ARISE) and Protocolized Care for Early Septic Shock (ProCESS) trials into derivation and validation cohorts. We trained machine learning models to predict individual absolute risk differences (iARDs) in 90-day mortality in derivation cohorts and tested for heterogeneity of treatment effect (HTE) in validation cohorts and swapped these cohorts in sensitivity analyses. We fit the best-performing model in a combined dataset to explore roles of patient characteristics and individual components of early goal-directed therapy (EGDT) to determine treatment responses.
settingEighty-one sites in Australia, New Zealand, Hong Kong, Finland, Republic of Ireland, and the United States. PATIENTS: Adult patients presenting to the emergency department with severe sepsis or septic shock.
interventionsEGDT vs. usual care. MEASUREMENTS AND MAIN
resultsA local-linear random forest model performed best in predicting iARDs. In the validation cohort, HTE was confirmed, evidenced by an interaction between iARD prediction and treatment ( p < 0.001). When patients were grouped based on predicted iARDs, treatment response increased from the lowest to the highest quintiles (absolute risk difference [95% CI], -8% [-19% to 4%] and relative risk reduction, 1.34 [0.89-2.01] in quintile 1 suggesting harm from EGDT, and 12% [1-23%] and 0.64 [0.42-0.96] in quintile 5 suggesting benefit). Sensitivity analyses showed similar findings. Pre-intervention albumin contributed the most to HTE. Analyses of individual EGDT components were inconclusive.
conclusionsTreatment response to EGDT varied across patients in two multicenter RCTs with large benefits for some patients while others were harmed. Patient characteristics, including albumin, were most important in identifying HTE.
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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.