Restricted or Liberal Fluid for Haemodynamic Resuscitation in Sepsis (FRESHLY)

Australian and New Zealand Intensive Care Research Centre

Status: Begins enrollment in 5 months

Conditions: Fluid Resuscitation; Septic Shock

Treatments: Other: Fluids; Other: Vasopressors

Study type: Observational

Funder types: Other

Identifiers

NCT05453565

FRESHLY V1

Details and patient eligibility

About

A prospective, individual patient data meta-analysis (IPDMA) of four multicentre, open-label, randomised clinical trials of initial haemodynamic resuscitation in patients with septic shock.

Full description

This study is a prospective, individual patient data meta-analysis (IPDMA) of four multicentre, open-label, randomised clinical trials of initial haemodynamic resuscitation in patients with septic shock.

The investigators will include four multicentre, open-label, randomised, clinical trials:

• Australasian Resuscitation in Sepsis Evaluation Fluids of Vasopressors in Emergency Department Sepsis (ARISE FLUIDS) trial conducted in Australia and New Zealand. ClinicalTrials.gov identifier NCT04569942
• Conservative versus Liberal Approach to fluid therapy of Septic Shock in intensive Care (CLASSIC) trial conducted in seven European countries. ClinicalTrials.gov identifier NCT03668236
• Crystalloid Liberal or Vasopressors Early (CLOVERS) trial conducted in the United States. ClinicalTrials.gov identifier NCT03434028
• Early Vasopressors in Sepsis (EVIS) trial conducted in the United Kingdom. ClinicalTrials.gov identifier NCT05179499

All four trials have all received relevant approval from a research ethics committee with a locally appropriate method of obtaining consent. These trials are prospectively chosen prior to the results of any individual trial being known because they are investigating the same broad question in patients with acute septic shock across several countries. The investigators of these trials collaborated to harmonise data and outcomes as far as possible across all trials to facilitate an IPDMA.

The aims to provide high level evidence to address the question of whether a fluid sparing/early vasopressor approach or a liberal fluid/later vasopressor approach to initial haemodynamic resuscitation in septic shock results in improved outcomes, including mortality.

Enrollment: 7,838 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Participants of the ARISE FLUIDS, CLASSIC, CLOVERS & EVIS trials who had:

• Suspected or proven infection
• Systolic blood pressure (SBP) <100 mm Hg OR mean arterial pressure (MAP) <65 mm Hg
• Lactate ≥ 2.0 mmol/L
• Requirement for vasopressors to meet perfusion targets

Exclusion criteria

Participants not in the ARISE FLUIDS, CLASSIC, CLOVERS & EVIS trials

Trial design

7,838 participants in 2 patient groups

Vasopressors

Description:

A haemodynamic resuscitation strategy based upon the restriction of IV fluids (by either volume or rate of infusion) with initiation or change of rate of vasopressors if required to meet perfusion targets

Treatment:

Other: Vasopressors

Fluids

Description:

A strategy of resuscitation with intravenous fluids as the primary intervention to achieve perfusion targets with subsequent initiation or change of rate of vasopressors if required.

Treatment:

Other: Fluids