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

Phase 3
Recruiting
Conditions
Shock, Septic
Interventions
Drug: Vasopressor
Other: Fluids
Registration Number
NCT04569942
Lead Sponsor
Australian and New Zealand Intensive Care Research Centre
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
1000
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
VasopressorVasopressora restricted fluids and early vasopressor strategy
FluidsFluidsa larger intravenous (IV) fluid volume and later vasopressor strategy
Primary Outcome Measures
NameTimeMethod
Days alive and out of hospitalFrom randomisation until 90 days post- randomization

the number of days alive and out of hospital at 90 days post randomization

Secondary Outcome Measures
NameTimeMethod
Death or disability at 6 monthsat 6 months post randomization

Death or disability as measured by the World Health Organization Disability Assessment Schedule (WHODAS)

Death or disability at 12 monthsat 12 months post randomization

Death or disability as measured by the World Health Organization Disability Assessment Schedule (WHODAS)

Time from randomization until deathFrom randomisation until 90 days post- randomization

Time from randomization until death

Ventilator-free days to day 28From randomisation until 28 days post- randomization

Number of days not on invasive mechanical ventilation

Vasopressor-free days to day 28From randomisation until 28 days post- randomization

Number of days not on vasopressors

Days alive and at homeFrom randomisation until 90 days post- randomization

Days alive and at home at 90 days post-randomisation

MortalityFrom randomisation until 90 days post- randomization

All-cause mortality

Renal replacement therapy-free days to day 28From randomisation until 28 days post- randomization

Number of days not on renal replacement therapy

Trial Locations

Locations (19)

St. Vincent's University Hospital

🇮🇪

Elm Park, Dublin, Ireland

Royal North Shore Hosptial

🇦🇺

Sydney, New South Wales, Australia

Bendigo Hospital

🇦🇺

Bendigo, Victoria, Australia

Box Hill Hospital

🇦🇺

Box Hill, Victoria, Australia

Austin Health

🇦🇺

Heidelberg, Victoria, Australia

Auckland City Hospital

🇳🇿

Auckland, North Island, New Zealand

John Hunter Hospital

🇦🇺

New Lambton Heights, New South Wales, Australia

Gold Coast University Hospital

🇦🇺

Southport, Queensland, Australia

The Queen Elizabeth Hospital

🇦🇺

Adelaide, South Australia, Australia

Maroondah Hospital

🇦🇺

Ringwood East, Victoria, Australia

Bankstown Hospital

🇦🇺

Bankstown, New South Wales, Australia

Mackay Base Hospital

🇦🇺

Mackay, Queensland, Australia

Alfred Hospital

🇦🇺

Melbourne, Victoria, Australia

Royal Prince Alfred Hospital

🇦🇺

Camperdown, New South Wales, Australia

Angliss Hospital

🇦🇺

Ferntree Gully, Victoria, Australia

Robina Hospital

🇦🇺

Robina, Queensland, Australia

Toowoomba Hospital

🇦🇺

Toowoomba, Queensland, Australia

St John of God Murdoch Hospital

🇦🇺

Murdoch, Western Australia, Australia

Royal Perth Hospital

🇦🇺

Perth, Western Australia, Australia

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