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

Shock, Septic Clinical Trial

— ARISE FLUIDS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04569942
• Other study ID #: ANZIC-RC/SP002
• Status: Recruiting
• Phase: Phase 3
• Start date: October 26, 2021
• Est. completion date: December 31, 2025

Study information

• Verified date: October 2023
• Source: Australian and New Zealand Intensive Care Research Centre
• Contact: Belinda D Howe, MPH
• Phone: 0399030340
• Email: belinda.howe[@]monash.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Emergencies
• Sepsis
• Shock, Septic

Intervention

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.

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.

Locations

Country	Name	City	State
Australia	The Queen Elizabeth Hospital	Adelaide	South Australia
Australia	Bankstown Hospital	Bankstown	New South Wales
Australia	Bendigo Hospital	Bendigo	Victoria
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Angliss Hospital	Ferntree Gully	Victoria
Australia	Austin Health	Heidelberg	Victoria
Australia	Mackay Base Hospital	Mackay	Queensland
Australia	Alfred Hospital	Melbourne	Victoria
Australia	St John of God Murdoch Hospital	Murdoch	Western Australia
Australia	John Hunter Hospital	New Lambton Heights	New South Wales
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Maroondah Hospital	Ringwood East	Victoria
Australia	Robina Hospital	Robina	Queensland
Australia	Gold Coast University Hospital	Southport	Queensland
Australia	Royal North Shore Hosptial	Sydney	New South Wales
Australia	Toowoomba Hospital	Toowoomba	Queensland

Sponsors (1)

Lead Sponsor	Collaborator
Australian and New Zealand Intensive Care Research Centre

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of invasive mechanical ventilation	Incidence of invasive mechanical ventilation	From randomisation until 90 days post- randomization
Other	Duration of invasive mechanical ventilation	Duration of invasive mechanical ventilation	From randomisation until 90 days post- randomization
Other	Incidence of acute renal replacement therapy	Incidence of acute renal replacement therapy	From randomisation until 90 days post- randomization
Other	Duration of acute renal replacement therapy	Duration of acute renal replacement therapy	From randomisation until 90 days post- randomization
Other	Incidence of vasopressor support	Incidence of vasopressor support	From randomisation until 90 days post- randomization
Other	Duration of vasopressor support	Duration of vasopressor support	From randomisation until 90 days post- randomization
Other	Emergency Department length of stay	Emergency Department length of stay	From randomisation until 90 days post- randomization
Other	Intensive care unit length of stay	Intensive care unit length of stay	From randomisation until 90 days post- randomization
Other	Hospital length of stay	Hospital length of stay	From randomisation until 90 days post- randomization
Other	In hospital mortality	Patients who die in hospital	From randomisation until 90 days post- randomization
Other	Mortality at 6 months	mortality at 6 months	6 Months post- randomization
Other	Mortality at 12 months	mortality at 12 months	1 year post- randomization
Other	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
Other	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
Other	Cost-effectiveness measured as cost/quality-adjusted life year (QALY)	cost effectiveness measured as cost per quality-adjusted life year	1 year post- randomization
Primary	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	Mortality	All-cause mortality	From randomisation until 90 days post- randomization
Secondary	Time from randomization until death	Time from randomization until death	From randomisation until 90 days post- randomization
Secondary	Days alive and at home	Days alive and at home at 90 days post-randomisation	From randomisation until 90 days post- randomization
Secondary	Ventilator-free days to day 28	Number of days not on invasive mechanical ventilation	From randomisation until 28 days post- randomization
Secondary	Vasopressor-free days to day 28	Number of days not on vasopressors	From randomisation until 28 days post- randomization
Secondary	Renal replacement therapy-free days to day 28	Number of days not on renal replacement therapy	From randomisation until 28 days post- randomization
Secondary	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
Secondary	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