NCT04569942

Brief Summary

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.

Trial Health

78
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,000

participants targeted

Target at P75+ for phase_3

Timeline
6mo left

Started Oct 2021

Longer than P75 for phase_3

Geographic Reach
3 countries

50 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress90%
Oct 2021Nov 2026

First Submitted

Initial submission to the registry

September 23, 2020

Completed
7 days until next milestone

First Posted

Study publicly available on registry

September 30, 2020

Completed
1.1 years until next milestone

Study Start

First participant enrolled

October 26, 2021

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2026

Completed
9 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 3, 2026

Expected
Last Updated

March 17, 2026

Status Verified

November 1, 2025

Enrollment Period

4.3 years

First QC Date

September 23, 2020

Last Update Submit

March 15, 2026

Conditions

Keywords

septic shockvasopressorResuscitation Fluids

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (8)

  • Mortality

    From randomisation until 90 days post- randomization

  • Time from randomization until death

    From randomisation until 90 days post- randomization

  • Days alive and at home

    From randomisation until 90 days post- randomization

  • Ventilator-free days to day 28

    From randomisation until 28 days post- randomization

  • Vasopressor-free days to day 28

    From randomisation until 28 days post- randomization

  • +3 more secondary outcomes

Other Outcomes (15)

  • Incidence of invasive mechanical ventilation

    From randomisation until 90 days post- randomization

  • Duration of invasive mechanical ventilation

    From randomisation until 90 days post- randomization

  • Incidence of acute renal replacement therapy

    From randomisation until 90 days post- randomization

  • +12 more other outcomes

Study Arms (2)

Vasopressor

ACTIVE COMPARATOR

a restricted fluids and early vasopressor strategy

Drug: Vasopressor

Fluids

ACTIVE COMPARATOR

a larger intravenous (IV) fluid volume and later vasopressor strategy

Other: Fluids

Interventions

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.

Vasopressor
FluidsOTHER

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.

Fluids

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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);
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (50)

Bankstown Hospital

Bankstown, New South Wales, 2200, Australia

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Nepean Hosital

Kingswood, New South Wales, 2747, Australia

Location

John Hunter Hospital

New Lambton Heights, New South Wales, 2305, Australia

Location

Port Macquarie Base Hospital

Port Macquarie, New South Wales, 2444, Australia

Location

Royal North Shore Hosptial

Sydney, New South Wales, 2065, Australia

Location

Ryde Hospital

Sydney, New South Wales, 2112, Australia

Location

Tamworth Hospital

Tamworth, New South Wales, 2340, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Royal Darwin & Palmerston Hospital

Darwin, Northern Territory, 0811, Australia

Location

The Prince Charles Hospital

Brisbane, Queensland, 4032, Australia

Location

QE II Jubilee Hospital

Brisbane, Queensland, 4108, Australia

Location

Bundaberg Hospital

Bundaberg, Queensland, 4670, Australia

Location

Caboolture Hospital

Caboolture, Queensland, 4510, Australia

Location

Cairns Hospital

Cairns, Queensland, 4870, Australia

Location

Hervey Bay Hospital

Hervey Bay, Queensland, 4655, Australia

Location

Ipswich Hospital

Ipswich, Queensland, 4305, Australia

Location

Mackay Base Hospital

Mackay, Queensland, 4740, Australia

Location

Robina Hospital

Robina, Queensland, 4226, Australia

Location

Gold Coast University Hospital

Southport, Queensland, 4215, Australia

Location

Sunshine Coast university hospital

Sunshine Coast, Queensland, 4560, Australia

Location

Toowoomba Hospital

Toowoomba, Queensland, 4350, Australia

Location

Townsville Hospital

Townsville, Queensland, 4810, Australia

Location

The Queen Elizabeth Hospital

Adelaide, South Australia, 5011, Australia

Location

Flinders Medical Centre

Streaky Bay, South Australia, 5025, Australia

Location

Ballarat Base Hospital

Ballarat, Victoria, 3353, Australia

Location

Bendigo Hospital

Bendigo, Victoria, 3550, Australia

Location

Casey Hospital

Berwick, Victoria, 3806, Australia

Location

Box Hill Hospital

Box Hill, Victoria, 3128, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Dandenong Hospital

Dandenong, Victoria, Australia

Location

Northern Hospital

Epping, Victoria, 3076, Australia

Location

Angliss Hospital

Ferntree Gully, Victoria, 3156, Australia

Location

St. Vincent's Hospital

Fitzroy, Victoria, 3065, Australia

Location

Barwon Health Geelong Hospital

Geelong, Victoria, 3220, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Maroondah Hospital

Ringwood East, Victoria, 3135, Australia

Location

Wangaratta Hospital

Wangaratta, Victoria, 3677, Australia

Location

Bunbury Hospital

Bunbury, Western Australia, 6230, Australia

Location

St John of God Hospital

Midland, Western Australia, 6056, Australia

Location

St John of God Murdoch Hospital

Murdoch, Western Australia, 6150, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

Fiona Stanley Hospital

Perth, Western Australia, 6150, Australia

Location

St. Vincent's University Hospital

Elm Park, Dublin, D04 T6F4, Ireland

Location

Auckland City Hospital

Auckland, North Island, 1023, New Zealand

Location

Dunedin Hospital

Dunedin, Otago, 9054, New Zealand

Location

Middlemore Hospital

Middlemore, Otahuhu, 1640, New Zealand

Location

Taranki Hospital

Hawera, 4640, New Zealand

Location

Wellington Hospital

Wellington, 2820, New Zealand

Location

Related Publications (1)

  • 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.

Related Links

MeSH Terms

Conditions

Shock, Septic

Interventions

Vasoconstrictor AgentsFluid Therapy

Condition Hierarchy (Ancestors)

SepsisInfectionsSystemic Inflammatory Response SyndromeInflammationPathologic ProcessesPathological Conditions, Signs and SymptomsShock

Intervention Hierarchy (Ancestors)

Cardiovascular AgentsTherapeutic UsesPharmacologic ActionsChemical Actions and UsesDrug TherapyTherapeutics

Study Officials

  • Sandra Peake, MBBS

    Monash University

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: randomized, controlled trial
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 23, 2020

First Posted

September 30, 2020

Study Start

October 26, 2021

Primary Completion

February 1, 2026

Study Completion (Estimated)

November 3, 2026

Last Updated

March 17, 2026

Record last verified: 2025-11

Data Sharing

IPD Sharing
Will share

all IPD that underlie results in a publication

Shared Documents
STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
Time Frame
IPD will be available one year after the publication date for a 2 year period
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.
More information

Locations