Australasian Resuscitation In Sepsis Evaluation: FLUid or Vasopressors In Emergency Department Sepsis (ARISE FLUIDS)

This multicentre, randomised controlled trial will enrol 1000 patients presenting with septic shock to the emergency department (ED) of participating hospitals in Australia and New Zealand. Participants will receive haemodynamic resuscitation with either a restricted fluids and early vasopressor regimen or a larger initial IV fluid volume with later introduction of vasopressors if required. Clinical care including the type of resuscitation fluid and vasopressor agent, will otherwise be in accordance with accepted standard care and according to clinician discretion. The study intervention will be delivered for at least 6 hours and up to 24 hours post-randomisation. Participants will be followed for up to 12 months and outcomes analysed on an intention-to-treat basis.

Study Overview

• Status: Active, not recruiting
• Conditions: Shock, Septic
• Intervention / Treatment: Drug: Vasopressor; Other: Fluids

Detailed Description

The ARISE FLUIDS study is a multicentre, randomised, parallel group clinical trial of a restricted fluids and early vasopressor strategy compared to a larger initial IV fluid volume and later vasopressors for the haemodynamic resuscitation of patients with septic shock presenting to the ED. It will be conducted in hospitals in Australia and New Zealand with 1000 patients recruited over a 3-year period.

Each patient meeting all of the inclusion and none of the exclusion criteria will be randomised to receive haemodynamic resuscitation using either a restricted fluid and early vasopressor regimen (vasopressors arm) or a larger initial fluid resuscitation volume (fluids arm) followed by later introduction of vasopressors (if required). The intervention will be commenced in the ED and delivered for at least 6 hours, and up to 24 hours post-randomisation if admitted to the ICU or other critical care area where the study protocol can be faithfully delivered. Treatment will revert to usual care as determined by the treating clinician when the patient is transferred to a non-critical care ward. All enrolled participants will be followed up and assessed for the defined study outcomes.

Participants will be identified using a systematic approach to screening and assessment of patients with possible sepsis presenting to the ED in accordance with standard clinical practice.

• Study Type: Interventional
• Enrollment (Actual): 1000
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Bankstown, New South Wales, Australia, 2200
      • Bankstown Hospital
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Kingswood, New South Wales, Australia, 2747
      • Nepean Hosital
    • New Lambton Heights, New South Wales, Australia, 2305
      • John Hunter Hospital
    • Port Macquarie, New South Wales, Australia, 2444
      • Port Macquarie Base Hospital
    • Sydney, New South Wales, Australia, 2065
      • Royal North Shore Hosptial
    • Sydney, New South Wales, Australia, 2112
      • Ryde Hospital
    • Tamworth, New South Wales, Australia, 2340
      • Tamworth Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Northern Territory
    • Darwin, Northern Territory, Australia, 0811
      • Royal Darwin & Palmerston Hospital
  • Queensland
    • Brisbane, Queensland, Australia, 4032
      • The Prince Charles Hospital
    • Brisbane, Queensland, Australia, 4108
      • QE II Jubilee Hospital
    • Bundaberg, Queensland, Australia, 4670
      • Bundaberg Hospital
    • Caboolture, Queensland, Australia, 4510
      • Caboolture Hospital
    • Cairns, Queensland, Australia, 4870
      • Cairns Hospital
    • Hervey Bay, Queensland, Australia, 4655
      • Hervey Bay Hospital
    • Ipswich, Queensland, Australia, 4305
      • Ipswich Hospital
    • Mackay, Queensland, Australia, 4740
      • Mackay Base Hospital
    • Robina, Queensland, Australia, 4226
      • Robina Hospital
    • Southport, Queensland, Australia, 4215
      • Gold Coast University Hospital
    • Sunshine Coast, Queensland, Australia, 4560
      • Sunshine Coast University Hospital
    • Toowoomba, Queensland, Australia, 4350
      • Toowoomba Hospital
    • Townsville, Queensland, Australia, 4810
      • Townsville Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5011
      • The Queen Elizabeth Hospital
    • Streaky Bay, South Australia, Australia, 5025
      • Flinders Medical Centre
  • Victoria
    • Ballarat, Victoria, Australia, 3353
      • Ballarat Base Hospital
    • Bendigo, Victoria, Australia, 3550
      • Bendigo Hospital
    • Berwick, Victoria, Australia, 3806
      • Casey Hospital
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre
    • Dandenong, Victoria, Australia
      • Dandenong Hospital
    • Epping, Victoria, Australia, 3076
      • Northern Hospital
    • Ferntree Gully, Victoria, Australia, 3156
      • Angliss Hospital
    • Fitzroy, Victoria, Australia, 3065
      • St. Vincent's Hospital
    • Geelong, Victoria, Australia, 3220
      • Barwon Health Geelong Hospital
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
    • Ringwood East, Victoria, Australia, 3135
      • Maroondah Hospital
    • Wangaratta, Victoria, Australia, 3677
      • Wangaratta Hospital
  • Western Australia
    • Bunbury, Western Australia, Australia, 6230
      • Bunbury Hospital
    • Midland, Western Australia, Australia, 6056
      • St John of God Hospital
    • Murdoch, Western Australia, Australia, 6150
      • St John of God Murdoch Hospital
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital
    • Perth, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
• Ireland
  • Dublin
    • Elm Park, Dublin, Ireland, D04 T6F4
      • St. Vincent's University Hospital
• New Zealand
  • Hawera, New Zealand, 4640
    • Taranki Hospital
  • Wellington, New Zealand, 2820
    • Wellington Hospital
  • North Island
    • Auckland, North Island, New Zealand, 1023
      • Auckland City Hospital
  • Otago
    • Dunedin, Otago, New Zealand, 9054
      • Dunedin Hospital
  • Otahuhu
    • Middlemore, Otahuhu, New Zealand, 1640
      • Middlemore Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Clinically suspected infection;
• Systolic blood pressure (SBP) <90 mm Hg or mean arterial pressure (MAP) <65 mm Hg, despite a ⩾1000ml cumulative total bolus of IV fluid administered over a maximum of 60 minutes; including pre-hospital boluses;
• Arterial or venous blood lactate >2.0 mmol/L;
• At least one dose of an intravenous antimicrobial has been commenced.

Exclusion Criteria:

• Age <18 years;
• Confirmed or suspected pregnancy;
• Transferred from another acute care facility;
• Hypotension suspected to be due to a non-sepsis cause;
• >2L total IV fluid administered (including prehospital fluids but excluding drugs and flushes);
• More than 6 hours has elapsed since presentation to the ED or more than 2 hours has elapsed since last inclusion criterion has been met;
• Treating clinician considers that one or both of the treatment regimens are not suitable for the patient or the study protocol cannot be delivered e.g. limitation of care, requirement for immediate surgery;
• Death is considered imminent or inevitable;
• Underlying disease that makes survival to 90 days unlikely;
• Inability to follow patient up to day-90 e.g. unstable accommodation, overseas visitor;
• Previously enrolled in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Vasopressor; a restricted fluids and early vasopressor strategy	Drug: Vasopressor; Cease IV fluid resuscitation. If persisting hypotension and/or hypoperfusion commence a vasopressor infusion (e.g. noradrenaline) and titrate according to local practice to achieve target MAP. The target MAP will be determined by the treating clinician. Reassess at least hourly for up to 6 hours post-randomisation, then as clinically required in conjunction with the protocol. Boluses of 250ml of IV fluids are permitted if deemed indicated by the treating clinician.
Active Comparator: Fluids; a larger intravenous (IV) fluid volume and later vasopressor strategy	Other: Fluids; An fluid bolus of up to 1000ml will be administered over a maximum of 1 hour, if required, for persisting hypotension and/or hypoperfusion. Reassess at least hourly to 6 hours post-randomisation, then as clinically required in conjunction with the protocol. Further IV fluid boluses of 500ml are recommended as clinically indicated to achieve the target MAP. The target MAP will be determined by the treating clinician. Haemodynamic resuscitation will be guided by usual clinical assessment including vital signs, mentation, perfusion, and urine output until the treating clinician determines fluid resuscitation is no longer clinically required. A minimum of 2-3 L (30 ml/kg), including pre-randomisation fluids, is recommended within 3 hours of ED arrival consistent with the SSC guidelines, unless clinically contraindicated. Vasopressors may be commenced if blood pressure remains below target despite optimal fluid resuscitation as determined by the treating clinician.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days alive and out of hospital	the number of days alive and out of hospital at 90 days post randomization	From randomisation until 90 days post- randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	All-cause mortality	From randomisation until 90 days post- randomization
Time from randomization until death	Time from randomization until death	From randomisation until 90 days post- randomization
Days alive and at home	Days alive and at home at 90 days post-randomisation	From randomisation until 90 days post- randomization
Ventilator-free days to day 28	Number of days not on invasive mechanical ventilation	From randomisation until 28 days post- randomization
Vasopressor-free days to day 28	Number of days not on vasopressors	From randomisation until 28 days post- randomization
Renal replacement therapy-free days to day 28	Number of days not on renal replacement therapy	From randomisation until 28 days post- randomization
Death or disability at 6 months	Death or disability as measured by the World Health Organization Disability Assessment Schedule (WHODAS)	at 6 months post randomization
Death or disability at 12 months	Death or disability as measured by the World Health Organization Disability Assessment Schedule (WHODAS)	at 12 months post randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of invasive mechanical ventilation	Incidence of invasive mechanical ventilation	From randomisation until 90 days post- randomization
Duration of invasive mechanical ventilation	Duration of invasive mechanical ventilation	From randomisation until 90 days post- randomization
Incidence of acute renal replacement therapy	Incidence of acute renal replacement therapy	From randomisation until 90 days post- randomization
Duration of acute renal replacement therapy	Duration of acute renal replacement therapy	From randomisation until 90 days post- randomization
Incidence of vasopressor support	Incidence of vasopressor support	From randomisation until 90 days post- randomization
Duration of vasopressor support	Duration of vasopressor support	From randomisation until 90 days post- randomization
Emergency Department length of stay	Emergency Department length of stay	From randomisation until 90 days post- randomization
Intensive care unit length of stay	Intensive care unit length of stay	From randomisation until 90 days post- randomization
Hospital length of stay	Hospital length of stay	From randomisation until 90 days post- randomization
In hospital mortality	Patients who die in hospital	From randomisation until 90 days post- randomization
Mortality at 6 months	mortality at 6 months	6 Months post- randomization
Mortality at 12 months	mortality at 12 months	1 year post- randomization
Quality of life at 6 months	Patient quality of life as measured by the EuroQol Group 5 dimensions 5 levels survey (EQ-5D-5L)	6 months post- randomization
Quality of life at 12 months	Patient quality of life as measured by the EuroQol Group 5 dimensions 5 levels survey (EQ-5D-5L)	1 year post- randomization
Cost-effectiveness measured as cost/quality-adjusted life year (QALY)	cost effectiveness measured as cost per quality-adjusted life year	1 year post- randomization

Collaborators and Investigators

• Sponsor: Australian and New Zealand Intensive Care Research Centre
• Investigators: Study Chair: Sandra Peake, MBBS, Monash University

Publications and helpful links

General Publications

• Howe BD, Macdonald SPJ, Arendts G, Bellomo R, Burcham J, Delaney A, Egerton-Warburton D, Fatovich D, Fraser JF, Higgins A, Jones P, Keijzers G, Milford E, Udy AA, Williams P, Young P, Peake SL. Australasian Resuscitation In Sepsis Evaluation: FLUid or vasopressors In emergency Department Sepsis (ARISE FLUIDS) trial: study protocol. BMJ Open. 2025 Jul 20;15(7):e101215. doi: 10.1136/bmjopen-2025-101215.

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2021
• Primary Completion (Actual): February 1, 2026
• Study Completion (Estimated): November 3, 2026

Study Registration Dates

• First Submitted: September 23, 2020
• First Submitted That Met QC Criteria: September 28, 2020
• First Posted (Actual): September 30, 2020

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 15, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: septic shock; vasopressor; Resuscitation Fluids
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Pathological Conditions, Signs and Symptoms; Shock, Septic; Therapeutics; Drug Therapy; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Cardiovascular Agents; Vasoconstrictor Agents; Fluid Therapy
• Other Study ID Numbers: ANZIC-RC/SP002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: all IPD that underlie results in a publication
• IPD Sharing Time Frame: IPD will be available one year after the publication date for a 2 year period
• IPD Sharing Access Criteria: Data requests can be submitted to the ARISE FLUIDS Management Committee, via the project manager, Ms Belinda Howe, at belinda.howe@monash.edu. The data will be made available following the submission of an appropriate research question, approval of the application by the ARISE FLUIDS management committee, and execution of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No