Clinical trial NCT04569942: Australasian Resuscitation In Sepsis Evaluation: FLUid or Vasopressors In Emergency Department Sepsis
Official title: Australasian Resuscitation In Sepsis Evaluation: FLUid or Vasopressors In Emergency Department Sepsis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Shock, Septic
Keywords: septic shock
vasopressor
Resuscitation Fluids
Lead sponsor: Australian and New Zealand Intensive Care Research Centre
Sponsor class: OTHER
First posted: 2020-09-30
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized, controlled trial
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Days alive and out of hospital
timeFrame: From randomisation until 90 days post- randomization
Secondary outcomes:
measure: Mortality
timeFrame: From randomisation until 90 days post- randomization
measure: Time from randomization until death
timeFrame: From randomisation until 90 days post- randomization
measure: Days alive and at home
timeFrame: From randomisation until 90 days post- randomization
measure: Ventilator-free days to day 28
timeFrame: From randomisation until 28 days post- randomization
measure: Vasopressor-free days to day 28
timeFrame: From randomisation until 28 days post- randomization
measure: Renal replacement therapy-free days to day 28
timeFrame: From randomisation until 28 days post- randomization
measure: Death or disability at 6 months
timeFrame: at 6 months post randomization
measure: Death or disability at 12 months
timeFrame: at 12 months post randomization
Other outcomes:
measure: Incidence of invasive mechanical ventilation
timeFrame: From randomisation until 90 days post- randomization
measure: Duration of invasive mechanical ventilation
timeFrame: From randomisation until 90 days post- randomization
measure: Incidence of acute renal replacement therapy
timeFrame: From randomisation until 90 days post- randomization
measure: Duration of acute renal replacement therapy
timeFrame: From randomisation until 90 days post- randomization
measure: Incidence of vasopressor support
timeFrame: From randomisation until 90 days post- randomization
measure: Duration of vasopressor support
timeFrame: From randomisation until 90 days post- randomization
measure: Emergency Department length of stay
timeFrame: From randomisation until 90 days post- randomization
measure: Intensive care unit length of stay
timeFrame: From randomisation until 90 days post- randomization
measure: Hospital length of stay
timeFrame: From randomisation until 90 days post- randomization
measure: In hospital mortality
timeFrame: From randomisation until 90 days post- randomization
measure: Mortality at 6 months
timeFrame: 6 Months post- randomization
measure: Mortality at 12 months
timeFrame: 1 year post- randomization
measure: Quality of life at 6 months
timeFrame: 6 months post- randomization
measure: Quality of life at 12 months
timeFrame: 1 year post- randomization
measure: Cost-effectiveness measured as cost/quality-adjusted life year (QALY)
timeFrame: 1 year post- randomization
Locations:
city: Bankstown
country: Australia
facility: Bankstown Hospital
state: New South Wales
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: New Lambton Heights
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Royal North Shore Hosptial
state: New South Wales
city: Mackay
country: Australia
facility: Mackay Base Hospital
state: Queensland
city: Robina
country: Australia
facility: Robina Hospital
state: Queensland
city: Southport
country: Australia
facility: Gold Coast University Hospital
state: Queensland
city: Toowoomba
country: Australia
facility: Toowoomba Hospital
state: Queensland
city: Adelaide
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Bendigo
country: Australia
facility: Bendigo Hospital
state: Victoria
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Ferntree Gully
country: Australia
facility: Angliss Hospital
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
city: Ringwood East
country: Australia
facility: Maroondah Hospital
state: Victoria
city: Murdoch
country: Australia
facility: St John of God Murdoch Hospital
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Elm Park
country: Ireland
facility: St. Vincent's University Hospital
state: Dublin
city: Auckland
country: New Zealand
facility: Auckland City Hospital
state: North Island
Study officials:
affiliation: Monash University
name: Sandra Peake, MBBS
role: STUDY_CHAIR
References: