Shock, SepticPhase 3ARISE FLUIDSNCT04569942
Australasian Resuscitation In Sepsis Evaluation: FLUid or Vasopressors In Emergency Department Sepsis
A Phase 3 study testing Vasopressor and Fluids in people with Shock, Septic, run by Australian and New Zealand Intensive Care Research Centre at 50 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Shock, Septic
- What is being tested?
- Vasopressor and Fluids
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,000 participants
- Where
- 50 sitesin 3 countries
- Study dates
- 26 Oct 2021to 3 Nov 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
Show all 11Show fewer
- 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.
Trial locations and contacts
50 sites in 3 countries.
50 sites in 3 countries
Australia44 sites
The Queen Elizabeth Hospital
Adelaide, South Australia, 5011
Ballarat Base Hospital
Ballarat, Victoria, 3353
Bankstown Hospital
Bankstown, New South Wales, 2200
Bendigo Hospital
Bendigo, Victoria, 3550
Casey Hospital
Berwick, Victoria, 3806
Box Hill Hospital
Box Hill, Victoria, 3128
The Prince Charles Hospital
Brisbane, Queensland, 4032
QE II Jubilee Hospital
Brisbane, Queensland, 4108
Bunbury Hospital
Bunbury, Western Australia, 6230
Bundaberg Hospital
Bundaberg, Queensland, 4670
Caboolture Hospital
Caboolture, Queensland, 4510
Cairns Hospital
Cairns, Queensland, 4870
Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050
Monash Medical Centre
Clayton, Victoria, 3168
Dandenong Hospital
Dandenong, Victoria
Royal Darwin & Palmerston Hospital
Darwin, Northern Territory, 0811
Northern Hospital
Epping, Victoria, 3076
Angliss Hospital
Ferntree Gully, Victoria, 3156
St. Vincent's Hospital
Fitzroy, Victoria, 3065
Barwon Health Geelong Hospital
Geelong, Victoria, 3220
Hervey Bay Hospital
Hervey Bay, Queensland, 4655
Ipswich Hospital
Ipswich, Queensland, 4305
Nepean Hosital
Kingswood, New South Wales, 2747
Mackay Base Hospital
Mackay, Queensland, 4740
Alfred Hospital
Melbourne, Victoria, 3004
St John of God Hospital
Midland, Western Australia, 6056
St John of God Murdoch Hospital
Murdoch, Western Australia, 6150
John Hunter Hospital
New Lambton Heights, New South Wales, 2305
Royal Melbourne Hospital
Parkville, Victoria, 3050
Royal Perth Hospital
Perth, Western Australia, 6000
Fiona Stanley Hospital
Perth, Western Australia, 6150
Port Macquarie Base Hospital
Port Macquarie, New South Wales, 2444
Maroondah Hospital
Ringwood East, Victoria, 3135
Robina Hospital
Robina, Queensland, 4226
Gold Coast University Hospital
Southport, Queensland, 4215
Flinders Medical Centre
Streaky Bay, South Australia, 5025
Sunshine Coast university hospital
Sunshine Coast, Queensland, 4560
Royal North Shore Hosptial
Sydney, New South Wales, 2065
Ryde Hospital
Sydney, New South Wales, 2112
Tamworth Hospital
Tamworth, New South Wales, 2340
Toowoomba Hospital
Toowoomba, Queensland, 4350
Townsville Hospital
Townsville, Queensland, 4810
Wangaratta Hospital
Wangaratta, Victoria, 3677
Westmead Hospital
Westmead, New South Wales, 2145
New Zealand5 sites
Auckland City Hospital
Auckland, North Island, 1023
Dunedin Hospital
Dunedin, Otago, 9054
Taranki Hospital
Hawera, 4640
Middlemore Hospital
Middlemore, Otahuhu, 1640
Wellington Hospital
Wellington, 2820
About this study
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.
Read the 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
- Being tested
- Vasopressor, Fluids
- Keywords
- septic shock, vasopressor, Resuscitation Fluids
- Medical subject headings
- Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VasopressorDrug
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.
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.
| Study group | Role | What they receive |
|---|---|---|
| Vasopressor | Active comparator | a restricted fluids and early vasopressor strategy Receives: Drug: Vasopressor |
| Fluids | Active comparator | a larger intravenous (IV) fluid volume and later vasopressor strategy Receives: Other: Fluids |
What is being measured
The primary outcome is the main question the study is designed to answer.
Days alive and out of hospital
the number of days alive and out of hospital at 90 days post randomization
Measured: From randomisation until 90 days post- randomization
Secondary outcomes (8)
Mortality
All-cause mortality
Measured: From randomisation until 90 days post- randomization
Time from randomization until death
Time from randomization until death
Measured: From randomisation until 90 days post- randomization
Days alive and at home
Days alive and at home at 90 days post-randomisation
Measured: From randomisation until 90 days post- randomization
Ventilator-free days to day 28
Number of days not on invasive mechanical ventilation
Measured: From randomisation until 28 days post- randomization
Vasopressor-free days to day 28
Number of days not on vasopressors
Measured: From randomisation until 28 days post- randomization
Renal replacement therapy-free days to day 28
Number of days not on renal replacement therapy
Measured: 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)
Measured: 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)
Measured: at 12 months post randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2020
- Study start26 Oct 2021
- Primary completion1 Feb 2026
- Study completion3 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Shock, SepticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomized, controlled trial
- Masking
- None (open label)
- Enrolment
- 1,000 participants (actual)
Sponsor and investigators
- Lead sponsor
- Australian and New Zealand Intensive Care Research Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sandra Peake, MBBS, Study chair, Monash University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04569942
- Sponsor's protocol ID
- ANZIC-RC/SP002
- Acronym
- ARISE FLUIDS
- Status last verified
- Nov 2025
- First submitted
- 23 Sep 2020
- Last updated
- 17 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: all IPD that underlie results in a publication
Publications
ARISE FLUIDS Investigators, the ANZICS Clinical Trials Group, and the ACEM Clinical Trials Network; Peake SL, Macdonald SPJ, Howe BD, Milford E, Jones P, Arendts G, Bailey M, Burcham J, Delaney A, Egerton-Warburton D, Fatovich D, Fraser JF, Higgins AM, Keijzers G, Udy AA, Williams P, Young PJ, Bellomo R. Vasopressors or Fluids in Early Septic Shock. N Engl J Med. 2026 Jun 11. doi: 10.1056/NEJMoa2516225. Online ahead of print.
PubMed 42274006Howe 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.
PubMed 40685240
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Australasian Resuscitation In Sepsis Evaluation: FLUid or Vasopressors In Emergency Department Sepsis
- ClinicalTrials.gov ID
- NCT04569942
- Acronym / sponsor ID
- ARISE FLUIDS / ANZIC-RC/SP002
- Conditions
- Shock, Septic
- Keywords
- septic shock, vasopressor, Resuscitation Fluids
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 1,000 participants (actual)
- Lead sponsor
- Australian and New Zealand Intensive Care Research CentreUniversity, hospital or other
- Study start
- 26 Oct 2021 (actual)
- Primary completion
- 1 Feb 2026 (actual)
- Study completion
- 3 Nov 2026 (estimated)
- First posted
- 30 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- randomized, controlled trial
| Arm | Type | Receives |
|---|---|---|
| Vasopressor | Active comparator | Drug: Vasopressora restricted fluids and early vasopressor strategy |
| Fluids | Active comparator | Other: Fluidsa larger intravenous (IV) fluid volume and later vasopressor strategy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (11 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VasopressorCease 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. | Drug | Vasopressor |
| FluidsAn 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. | Other | Fluids |
Primary outcome
Days alive and out of hospital
Time frame: From randomisation until 90 days post- randomization
the number of days alive and out of hospital at 90 days post randomization
8 secondary outcomes
Mortality
Time frame: From randomisation until 90 days post- randomization
Time from randomization until death
Time frame: From randomisation until 90 days post- randomization
Days alive and at home
Time frame: From randomisation until 90 days post- randomization
Ventilator-free days to day 28
Time frame: From randomisation until 28 days post- randomization
Vasopressor-free days to day 28
Time frame: From randomisation until 28 days post- randomization
Renal replacement therapy-free days to day 28
Time frame: From randomisation until 28 days post- randomization
Death or disability at 6 months
Time frame: at 6 months post randomization
Death or disability at 12 months
Time frame: at 12 months post randomization
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2026.
- Derived from this study: PubMed 42274006ARISE FLUIDS Investigators, the ANZICS Clinical Trials Group, and the ACEM Clinical Trials Network; Peake SL, Macdonald SPJ, Howe BD, Milford E, Jones P, Arendts G, Bailey M, Burcham J, Delaney A, Egerton-Warburton D, Fatovich D, Fraser JF, Higgins AM, Keijzers G, Udy AA, Williams P, Young PJ, Bellomo R. Vasopressors or Fluids in Early Septic Shock. N Engl J Med. 2026 Jun 11. doi: 10.1056/NEJMoa2516225. Online ahead of print.
- Derived from this study: PubMed 40685240Howe 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.
- SAP for trialLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. all IPD that underlie results in a publication
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Sepsis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sandra Peake, MBBS study chair
Monash University
50 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Vasopressor and Fluids in people with Shock, Septic, run by Australian and New Zealand Intensive Care Research Centre at 50 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 17 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 50 sites in Australia, New Zealand, Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Days alive and out of hospital (time frame: From randomisation until 90 days post- randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04569942, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2026.