Australasian Resuscitation In Sepsis Evaluation: FLUid or Vasopressors In Emergency Department Sepsis (ARISE FLUIDS)

October 24, 2023 updated by: Australian and New Zealand Intensive Care Research Centre
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

1000

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Vasopressor
a restricted fluids and early vasopressor strategy
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.
Active Comparator: Fluids
a larger intravenous (IV) fluid volume and later vasopressor strategy
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
From randomisation until 90 days post- randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality
Time Frame: From randomisation until 90 days post- randomization
All-cause mortality
From randomisation until 90 days post- randomization
Time from randomization until death
Time Frame: From randomisation until 90 days post- randomization
Time from randomization until death
From randomisation until 90 days post- randomization
Days alive and at home
Time Frame: From randomisation until 90 days post- randomization
Days alive and at home at 90 days post-randomisation
From randomisation until 90 days post- randomization
Ventilator-free days to day 28
Time Frame: From randomisation until 28 days post- randomization
Number of days not on invasive mechanical ventilation
From randomisation until 28 days post- randomization
Vasopressor-free days to day 28
Time Frame: From randomisation until 28 days post- randomization
Number of days not on vasopressors
From randomisation until 28 days post- randomization
Renal replacement therapy-free days to day 28
Time Frame: From randomisation until 28 days post- randomization
Number of days not on renal replacement therapy
From randomisation until 28 days post- randomization
Death or disability at 6 months
Time Frame: at 6 months post randomization
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
Time Frame: at 12 months post randomization
Death or disability as measured by the World Health Organization Disability Assessment Schedule (WHODAS)
at 12 months post randomization

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of invasive mechanical ventilation
Time Frame: From randomisation until 90 days post- randomization
Incidence of invasive mechanical ventilation
From randomisation until 90 days post- randomization
Duration of invasive mechanical ventilation
Time Frame: From randomisation until 90 days post- randomization
Duration of invasive mechanical ventilation
From randomisation until 90 days post- randomization
Incidence of acute renal replacement therapy
Time Frame: From randomisation until 90 days post- randomization
Incidence of acute renal replacement therapy
From randomisation until 90 days post- randomization
Duration of acute renal replacement therapy
Time Frame: From randomisation until 90 days post- randomization
Duration of acute renal replacement therapy
From randomisation until 90 days post- randomization
Incidence of vasopressor support
Time Frame: From randomisation until 90 days post- randomization
Incidence of vasopressor support
From randomisation until 90 days post- randomization
Duration of vasopressor support
Time Frame: From randomisation until 90 days post- randomization
Duration of vasopressor support
From randomisation until 90 days post- randomization
Emergency Department length of stay
Time Frame: From randomisation until 90 days post- randomization
Emergency Department length of stay
From randomisation until 90 days post- randomization
Intensive care unit length of stay
Time Frame: From randomisation until 90 days post- randomization
Intensive care unit length of stay
From randomisation until 90 days post- randomization
Hospital length of stay
Time Frame: From randomisation until 90 days post- randomization
Hospital length of stay
From randomisation until 90 days post- randomization
In hospital mortality
Time Frame: From randomisation until 90 days post- randomization
Patients who die in hospital
From randomisation until 90 days post- randomization
Mortality at 6 months
Time Frame: 6 Months post- randomization
mortality at 6 months
6 Months post- randomization
Mortality at 12 months
Time Frame: 1 year post- randomization
mortality at 12 months
1 year post- randomization
Quality of life at 6 months
Time Frame: 6 months post- randomization
Patient quality of life as measured by the EuroQol Group 5 dimensions 5 levels survey (EQ-5D-5L)
6 months post- randomization
Quality of life at 12 months
Time Frame: 1 year post- randomization
Patient quality of life as measured by the EuroQol Group 5 dimensions 5 levels survey (EQ-5D-5L)
1 year post- randomization
Cost-effectiveness measured as cost/quality-adjusted life year (QALY)
Time Frame: 1 year post- randomization
cost effectiveness measured as cost per quality-adjusted life year
1 year post- randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Australian and New Zealand Intensive Care Research Centre

Investigators

  • Study Chair: Sandra Peake, MBBS, Monash University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 26, 2021

Primary Completion (Estimated)

December 31, 2024

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

September 23, 2020

First Submitted That Met QC Criteria

September 28, 2020

First Posted (Actual)

September 30, 2020

Study Record Updates

Last Update Posted (Actual)

October 26, 2023

Last Update Submitted That Met QC Criteria

October 24, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ANZIC-RC/SP002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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