Clinical trial NCT05453565: Restricted or Liberal Fluid for Haemodynamic Resuscitation in Sepsis
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
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Septic Shock
Fluid Resuscitation
Lead sponsor: Australian and New Zealand Intensive Care Research Centre
Sponsor class: OTHER
First posted: 2022-07-12
Enrollment: 7838
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: All trials include adult patients requiring resuscitation for hypotension or hypoperfusion due to suspected sepsis as defined in the original studies. Participants may be enrolled in the emergency department, acute care ward or intensive care unit.

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: All-cause mortality at 90 days post randomisation
timeFrame: 90 days
Secondary outcomes:
measure: Time from randomisation to death
timeFrame: Up to day 90
measure: Incidence of mechanical ventilation
timeFrame: from randomisation until day 90 post-randomisation
measure: Incidence of acute renal replacement therapy
timeFrame: from randomisation until day 90 post-randomisation
measure: Days alive free of organ support at 28 days post randomisation
timeFrame: from randomisation until day 28 post-randomisation
measure: Duration of hospital stay
timeFrame: From randomisation until day 90 post-randomisation
measure: Incidence of serious adverse events
timeFrame: from randomisation until day 90 post-randomisation
measure: Duration of intensive care unit (ICU) stay
timeFrame: From randomisation until day 90 post-randomisation
Other outcomes:
Locations:
Study officials:
References: