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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Shock, Septic

Intervention / Treatment
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* Drug: Vasopressor
* Other: Fluids


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized, controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vasopressor<br>a restricted fluids and early vasopressor strategy | Drug: Vasopressor<br>* 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.<br>|
| Active Comparator: Fluids<br>a larger intravenous (IV) fluid volume and later vasopressor strategy | Other: Fluids<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | All-cause mortality | From randomisation until 90 days post- randomization | 
| Time from randomization until death | Time from randomization until death | From randomisation until 90 days post- randomization | 
| Days alive and at home | Days alive and at home at 90 days post-randomisation | From randomisation until 90 days post- randomization | 
| Ventilator-free days to day 28 | Number of days not on invasive mechanical ventilation | From randomisation until 28 days post- randomization | 
| Vasopressor-free days to day 28 | Number of days not on vasopressors | From randomisation until 28 days post- randomization | 
| Renal replacement therapy-free days to day 28 | Number of days not on renal replacement therapy | 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) | 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) | at 12 months post randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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septic shock, vasopressor, Resuscitation Fluids