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Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis

Rowan, KM; Angus, DC; Bailey, M; Barnato, AE; Bellomo, R; Canter, RR; Coats, TJ; ... Yealy, DM; + view all (2017) Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis. New England Journal of Medicine , 376 (23) pp. 2223-2234. 10.1056/NEJMoa1701380. Green open access

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Abstract

BACKGROUND: After a single-center trial and observational studies suggesting that early, goal-directed therapy (EGDT) reduced mortality from septic shock, three multicenter trials (ProCESS, ARISE, and ProMISe) showed no benefit. This meta-analysis of individual patient data from the three recent trials was designed prospectively to improve statistical power and explore heterogeneity of treatment effect of EGDT. METHODS: We harmonized entry criteria, intervention protocols, outcomes, resource-use measures, and data collection across the trials and specified all analyses before unblinding. After completion of the trials, we pooled data, excluding the protocol-based standard-therapy group from the ProCESS trial, and resolved residual differences. The primary outcome was 90-day mortality. Secondary outcomes included 1-year survival, organ support, and hospitalization costs. We tested for treatment-by-subgroup interactions for 16 patient characteristics and 6 care-delivery characteristics. RESULTS: We studied 3723 patients at 138 hospitals in seven countries. Mortality at 90 days was similar for EGDT (462 of 1852 patients [24.9%]) and usual care (475 of 1871 patients [25.4%]); the adjusted odds ratio was 0.97 (95% confidence interval, 0.82 to 1.14; P=0.68). EGDT was associated with greater mean (±SD) use of intensive care (5.3±7.1 vs. 4.9±7.0 days, P=0.04) and cardiovascular support (1.9±3.7 vs. 1.6±2.9 days, P=0.01) than was usual care; other outcomes did not differ significantly, although average costs were higher with EGDT. Subgroup analyses showed no benefit from EGDT for patients with worse shock (higher serum lactate level, combined hypotension and hyperlactatemia, or higher predicted risk of death) or for hospitals with a lower propensity to use vasopressors or fluids during usual resuscitation. CONCLUSIONS: In this meta-analysis of individual patient data, EGDT did not result in better outcomes than usual care and was associated with higher hospitalization costs across a broad range of patient and hospital characteristics. (Funded by the National Institute of General Medical Sciences and others; PRISM ClinicalTrials.gov number, NCT02030158.)

Type: Article
Title: Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1056/NEJMoa1701380
Publisher version: http://dx.doi.org/10.1056/NEJMoa1701380
Language: English
Additional information: © 2017 Massachusetts Medical Society. All rights reserved.
Keywords: Science & Technology, Life Sciences & Biomedicine, Medicine, General & Internal, General & Internal Medicine, Severe Sepsis, Personalized Medicine, Mortality, Outcomes, Cohort, Trial
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1563650
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