Restricted or Liberal Fluid for Haemodynamic Resuscitation in Sepsis

Septic Shock Clinical Trial

— FRESHLY  

Official title:

Fluid Restricted Resuscitation in Sepsis With Hypotension Meta-Analysis (FRESHLY): Individual Patient Data Met-analysis of the ARISE FLUIDS, CLASSIC, CLOVERS and EVIS Trials

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05453565
• Other study ID #: FRESHLY V1
• Status: Not yet recruiting
• Start date: November 2024
• Est. completion date: November 2025

Study information

• Verified date: October 2023
• Source: Australian and New Zealand Intensive Care Research Centre
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 7838
• Est. completion date: November 2025
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Fluid Resuscitation
• Septic Shock
• Shock, Septic

Intervention

Other:
• Vasopressors
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
• Fluids
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Australian and New Zealand Intensive Care Research Centre

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All-cause mortality at 90 days post randomisation	Death from any cause at 90 days after randomisation	90 days
Secondary	Time from randomisation to death	Time from randomisation to death	Up to day 90
Secondary	Incidence of mechanical ventilation	Commencement of mechanical ventilation from randomisation until day 90 post-randomisation	from randomisation until day 90 post-randomisation
Secondary	Incidence of acute renal replacement therapy	Commencement of renal replacement therapy from randomisation until day 90 post-randomisation	from randomisation until day 90 post-randomisation
Secondary	Days alive free of organ support at 28 days post randomisation	days the patient is alive and receiving nil organ support from from randomisation until day 28 post-randomisation	from randomisation until day 28 post-randomisation
Secondary	Duration of hospital stay	Length of time in hospital from randomisation until death or hospital discharge or day 90 post-randomisation	From randomisation until day 90 post-randomisation
Secondary	Incidence of serious adverse events	Number of adverse events from randomisation until day 90 post-randomisation	from randomisation until day 90 post-randomisation
Secondary	Duration of intensive care unit (ICU) stay	Length of time in ICU from randomisation until death or hospital discharge or day 90 post-randomisation	From randomisation until day 90 post-randomisation