Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/17755
Title: REstricted Fluid REsuscitation in Sepsis-associated Hypotension (REFRESH): study protocol for a pilot randomised controlled trial.
Authors: Macdonald, Stephen P J;Taylor, David McD;Keijzers, Gerben;Arendts, Glenn;Fatovich, Daniel M;Kinnear, Frances B;Brown, Simon G A;Bellomo, Rinaldo;Burrows, Sally;Fraser, John F;Litton, Edward;Ascencio-Lane, Juan Carlos;Anstey, Matthew;McCutcheon, David;Smart, Lisa;Vlad, Ioana;Winearls, James;Wibrow, Bradley
Affiliation: Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, WA, Australia
Division of Emergency Medicine, Medical School, University of Western Australia, Perth, WA, Australia
Department of Emergency Medicine, Austin Health, Heidelberg, Victoria, Australia
Department of Medicine, University of Melbourne, Melbourne, VIC, Australia
Emergency Department, Gold Coast University Hospital, Gold Coast, QLD, Australia
School of Medicine, Bond University, Gold Coast, QLD, Australia
School of Medical Sciences, Griffith University, Gold Coast, QLD, Australia
Emergency Department, Fiona Stanley Hospital, Perth, WA, Australia
Emergency Department, Royal Perth Hospital, Perth, WA, Australia
Emergency and Children's Services, The Prince Charles Hospital, Brisbane, QLD, Australia
Emergency Department, Royal Hobart Hospital, Hobart, TAS, Australia
Intensive Care Unit, Austin Health, Heidelberg, Victoria, Australia
School of Medicine, University of Melbourne, Melbourne, VIC, Australia
School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia
School of Medicine, University of Queensland, Brisbane, QLD, Australia
Department of Intensive Care, Fiona Stanley Hospital, Perth, WA, Australia
Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia
Department of Intensive Care, Sir Charles Gairdner Hospital, Perth, WA, Australia
Emergency Department, Armadale Health Service, Perth, WA, Australia
Emergency Department, Sir Charles Gairdner Hospital, Perth, WA, Australia
Department of Intensive Care, Gold Coast University Hospital, Gold Coast, QLD, Australia
Issue Date: 29-Aug-2017
EDate: 2017
Citation: Trials 2017; 18(1): 399
Abstract: Guidelines recommend an initial intravenous (IV) fluid bolus of 30 ml/kg isotonic crystalloid for patients with sepsis and hypotension. However, there is a lack of evidence from clinical trials to support this. Accumulating observational data suggest harm associated with the injudicious use of fluids in sepsis. There is currently equipoise regarding liberal or restricted fluid-volume resuscitation as first-line treatment for sepsis-related hypotension. A randomised trial comparing these two approaches is, therefore, justified. The REstricted Fluid REsuscitation in Sepsis-associated Hypotension trial (REFRESH) is a multicentre, open-label, randomised, phase II clinical feasibility trial. Participants will be patients presenting to the emergency departments of Australian metropolitan hospitals with suspected sepsis and a systolic blood pressure of < 100 mmHg, persisting after a 1000-ml fluid bolus with isotonic crystalloid. Participants will be randomised to either a second 1000-ml fluid bolus (standard care) or maintenance rate fluid only, with the early commencement of a vasopressor infusion to maintain a mean arterial pressure of > 65 mmHg, if required (restricted fluid). All will receive further protocolised fluid boluses (500 ml or 250 ml, respectively), if required during the 6-h study period. The primary outcome measure is total volume administered in the first 6 h. Secondary outcomes include fluid volume at 24 h, organ support 'free days' to day 28, 90-day mortality, and a range of feasibility and process-of-care measures. Participants will also undergo serial measurement, over the first 24 h, of biomarkers of inflammation, endothelial cell activation and glycocalyx degradation for comparison between the groups. This is the first randomised trial examining fluid volume for initial resuscitation in septic shock in an industrialised country. A pragmatic, open-label design will establish the feasibility of undertaking a large, international, multicentre trial with sufficient power to assess clinical outcomes. The embedded biomarker study aims to provide mechanistic plausibility for a larger trial by defining the effects of fluid volume on markers of systemic inflammation and the vascular endothelium. Australia and New Zealand Clinical Trials Registry, ID: ACTRN12616000006448. Registered on 12 January 2016.
URI: http://ahro.austin.org.au/austinjspui/handle/1/17755
DOI: 10.1186/s13063-017-2137-7
ORCID: 0000-0002-8986-9997
0000-0002-1650-8939
PubMed URL: 28851407
Type: Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Subjects: Fluid therapy
Hypotension
Sepsis
Appears in Collections:Journal articles

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