Protocolised Management In Sepsis (ProMISe):A multicentre randomised controlled trial of the clinical effectiveness and cost-effectiveness of early, goal-directed, protocolised resuscitation for emerging septic shock

Paul R. Mouncey, Tiffany M. Osborn, G. Sarah Power, David A. Harrison, M. Zia Sadique, Richard D. Grieve, Rahi Jahan, Jermaine C.K. Tan, Sheila E. Harvey, Derek Bell, Julian F. Bion, Timothy J. Coats, Mervyn Singer, J. Duncan Young, Kathryn M. Rowan

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

Background: Early goal-directed therapy (EGDT) is recommended in international uidance for the resuscitation of patients presenting with early septic shock. However, adoption has been limited and uncertainty remains over its clinical effectiveness and cost-effectiveness. Objectives: The primary objective was to estimate the effect of EGDT compared with usual resuscitation on mortality at 90 days following randomisation and on incremental cost-effectiveness at 1 year. The secondary objectives were to compare EGDT with usual resuscitation for requirement for, and duration of, critical care unit organ support; length of stay in the emergency department (ED), critical care unit and acute hospital; health-related quality of life, resource use and costs at 90 days and at 1 ear; all-cause mortality at 28 days, at acute hospital discharge and at 1 year; and estimated lifetime incremental cost-effectiveness. Design: A pragmatic, open, multicentre, parallel-group randomised controlled trial with an integrated economic evaluation. Setting: Fifty-six NHS hospitals in England. Participants: A total of 1260 patients who presented at EDs with septic shock. Interventions: EGDT (n = 630) or usual resuscitation (n = 630). Patients were randomly allocated 1 : 1. Main outcome measures: All-cause mortality at 90 days after randomisation and incremental net benefit (at £20,000 per quality-adjusted life-year) at 1 year. Results: Following withdrawals, data on 1243 (EGDT, n = 623; usual resuscitation, n = 620) patients were included in the nalysis. By 90 days, 184 (29.5%) in the EGDT and 181 (29.2%) patients in the usual-resuscitation group had died [p = 0.90; absolute risk reduction −0.3%, 95% confidence interval (CI) −5.4 to 4.7; relative risk 1.01, 95% CI 0.85 to 1.20]. Treatment intensity was greater for the EGDT group, indicated by the increased use of intravenous fluids, vasoactive drugs and red blood cell transfusions. Increased treatment intensity was reflected by significantly higher Sequential Organ Failure Assessment scores and more advanced cardiovascular support days in critical care for the EGDT group. At 1 year, the incremental net benefit for EGDT versus usual resuscitation was negative at −£725 (95% CI −£3000 to £1550). The probability that EGDT was more cost-effective than usual resuscitation was below 30%. There were no significant differences in any other secondary outcomes, including health-related quality of life, or adverse events. Limitations: Recruitment was lower at weekends and out of hours. The intervention could not be blinded. Conclusions: There was no significant difference in all-cause mortality at 90 days for EGDT compared with usual resuscitation among adults identified with early septic shock presenting to EDs in England. On average, costs were higher in the EGDT group than in the usual-resuscitation group while quality-adjusted life-years were similar in both groups; the probability that it is cost-effective is < 30%.

Original languageEnglish
Pages (from-to)1-150
Number of pages150
JournalHealth Technology Assessment
Volume19
Issue number97
DOIs
StatePublished - Nov 2015

Fingerprint

Dive into the research topics of 'Protocolised Management In Sepsis (ProMISe):A multicentre randomised controlled trial of the clinical effectiveness and cost-effectiveness of early, goal-directed, protocolised resuscitation for emerging septic shock'. Together they form a unique fingerprint.

Cite this