Australasian Resuscitation In Sepsis Evaluation: FLUid or Vasopressors In Emergency Department Sepsis

NCT ID: NCT04569942

Last Updated: 2025-11-21

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 1000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-26
• Study Completion Date: 2026-11-03

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.

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.

Conditions

Shock, Septic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vasopressor

a restricted fluids and early vasopressor strategy

Group Type: ACTIVE_COMPARATOR

Vasopressor

Intervention Type: DRUG

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.

Fluids

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

Group Type: ACTIVE_COMPARATOR

Fluids

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Australian and New Zealand Intensive Care Research Centre

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sandra Peake, MBBS

Role: STUDY_CHAIR

Monash University

Locations

Bankstown Hospital

Bankstown, New South Wales, Australia

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Nepean Hosital

Kingswood, New South Wales, Australia

John Hunter Hospital

New Lambton Heights, New South Wales, Australia

Port Macquarie Base Hospital

Port Macquarie, New South Wales, Australia

Royal North Shore Hosptial

Sydney, New South Wales, Australia

Ryde Hospital

Sydney, New South Wales, Australia

Tamworth Hospital

Tamworth, New South Wales, Australia

Westmead Hospital

Westmead, New South Wales, Australia

Royal Darwin & Palmerston Hospital

Darwin, Northern Territory, Australia

The Prince Charles Hospital

Brisbane, Queensland, Australia

QE II Jubilee Hospital

Brisbane, Queensland, Australia

Bundaberg Hospital

Bundaberg, Queensland, Australia

Caboolture Hospital

Caboolture, Queensland, Australia

Cairns Hospital

Cairns, Queensland, Australia

Hervey Bay Hospital

Hervey Bay, Queensland, Australia

Ipswich Hospital

Ipswich, Queensland, Australia

Mackay Base Hospital

Mackay, Queensland, Australia

Robina Hospital

Robina, Queensland, Australia

Gold Coast University Hospital

Southport, Queensland, Australia

Sunshine Coast university hospital

Sunshine Coast, Queensland, Australia

Toowoomba Hospital

Toowoomba, Queensland, Australia

Townsville Hospital

Townsville, Queensland, Australia

The Queen Elizabeth Hospital

Adelaide, South Australia, Australia

Flinders Medical Centre

Streaky Bay, South Australia, Australia

Ballarat Base Hospital

Ballarat, Victoria, Australia

Bendigo Hospital

Bendigo, Victoria, Australia

Casey Hospital

Berwick, Victoria, Australia

Box Hill Hospital

Box Hill, Victoria, Australia

Monash Medical Centre

Clayton, Victoria, Australia

Dandenong Hospital

Dandenong, Victoria, Australia

Northern Hospital

Epping, Victoria, Australia

Angliss Hospital

Ferntree Gully, Victoria, Australia

St. Vincent's Hospital

Fitzroy, Victoria, Australia

Barwon Health Geelong Hospital

Geelong, Victoria, Australia

Alfred Hospital

Melbourne, Victoria, Australia

Royal Melbourne Hospital

Parkville, Victoria, Australia

Maroondah Hospital

Ringwood East, Victoria, Australia

Wangaratta Hospital

Wangaratta, Victoria, Australia

Bunbury Hospital

Bunbury, Western Australia, Australia

St John of God Hospital

Midland, Western Australia, Australia

St John of God Murdoch Hospital

Murdoch, Western Australia, Australia

Royal Perth Hospital

Perth, Western Australia, Australia

Fiona Stanley Hospital

Perth, Western Australia, Australia

St. Vincent's University Hospital

Elm Park, Dublin, Ireland

Auckland City Hospital

Auckland, North Island, New Zealand

Dunedin Hospital

Dunedin, Otago, New Zealand

Middlemore Hospital

Middlemore, Otahuhu, New Zealand

Taranki Hospital

Hawera, , New Zealand

Wellington Hospital

Wellington, , New Zealand

Countries

Australia; Ireland; New Zealand

References

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.

Reference Type: DERIVED

PMID: 40685240 (View on PubMed)

Other Identifiers

ANZIC-RC/SP002

Identifier Type: -

Identifier Source: org_study_id