Septic ShockFRESHLYNCT05453565
Restricted or Liberal Fluid for Haemodynamic Resuscitation in Sepsis
An observational study of Septic Shock and Fluid Resuscitation, run by Australian and New Zealand Intensive Care Research Centre.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock, Fluid Resuscitation
- What is being tested?
- Vasopressors and Fluids
- Type of treatment
- Injection or infusion
- How many people
- 7,838 participants
- Where
- No sites listed yet
- Study dates
- Nov 2025to Nov 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- Participants not in the ARISE FLUIDS, CLASSIC, CLOVERS \& EVIS trials
About this study
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
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.
Read the 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.
- Conditions
- Septic Shock, Fluid Resuscitation
- Being tested
- Vasopressors, Fluids
- Medical subject headings
- Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VasopressorsOther
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
FluidsOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Other: Vasopressors | |
| 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. Receives: Other: Fluids |
What is being measured
The primary outcome is the main question the study is designed to answer.
All-cause mortality at 90 days post randomisation
Death from any cause at 90 days after randomisation
Measured: 90 days
Secondary outcomes (7)
Time from randomisation to death
Time from randomisation to death
Measured: Up to day 90
Incidence of mechanical ventilation
Commencement of mechanical ventilation from randomisation until day 90 post-randomisation
Measured: from randomisation until day 90 post-randomisation
Incidence of acute renal replacement therapy
Commencement of renal replacement therapy from randomisation until day 90 post-randomisation
Measured: from randomisation until day 90 post-randomisation
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
Measured: from randomisation until day 28 post-randomisation
Duration of hospital stay
Length of time in hospital from randomisation until death or hospital discharge or day 90 post-randomisation
Measured: From randomisation until day 90 post-randomisation
Incidence of serious adverse events
Number of adverse events from randomisation until day 90 post-randomisation
Measured: from randomisation until day 90 post-randomisation
Duration of intensive care unit (ICU) stay
Length of time in ICU from randomisation until death or hospital discharge or day 90 post-randomisation
Measured: From randomisation until day 90 post-randomisation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2022
- Study startNov 2025 (estimated)
- Primary completionNov 2026 (estimated)
- Study completionNov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Other
- Enrolment
- 7,838 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Australian and New Zealand Intensive Care Research Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05453565
- Sponsor's protocol ID
- FRESHLY V1
- Acronym
- FRESHLY
- Status last verified
- Jan 2025
- First submitted
- 3 Jun 2022
- Last updated
- 3 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05453565
- Acronym / sponsor ID
- FRESHLY / FRESHLY V1
- Conditions
- Septic Shock, Fluid Resuscitation
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 7,838 participants (estimated)
- Lead sponsor
- Australian and New Zealand Intensive Care Research CentreUniversity, hospital or other
- Study start
- Nov 2025 (estimated)
- Primary completion
- Nov 2026 (estimated)
- Study completion
- Nov 2026 (estimated)
- First posted
- 12 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Other
- Time perspective
- Other
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vasopressors | – | Other: VasopressorsA 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 | – | Other: FluidsA 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (1 listed)
- Participants not in the ARISE FLUIDS, CLASSIC, CLOVERS \& EVIS trials
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VasopressorsA 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 | Other | Vasopressors |
| FluidsA 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. | Other | Fluids |
Primary outcome
All-cause mortality at 90 days post randomisation
Time frame: 90 days
Death from any cause at 90 days after randomisation
7 secondary outcomes
Time from randomisation to death
Time frame: Up to day 90
Incidence of mechanical ventilation
Time frame: from randomisation until day 90 post-randomisation
Incidence of acute renal replacement therapy
Time frame: from randomisation until day 90 post-randomisation
Days alive free of organ support at 28 days post randomisation
Time frame: from randomisation until day 28 post-randomisation
Duration of hospital stay
Time frame: From randomisation until day 90 post-randomisation
Incidence of serious adverse events
Time frame: from randomisation until day 90 post-randomisation
Duration of intensive care unit (ICU) stay
Time frame: From randomisation until day 90 post-randomisation
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Septic Shock and Fluid Resuscitation, run by Australian and New Zealand Intensive Care Research Centre.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 3 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
All-cause mortality at 90 days post randomisation (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2025; AzTrials last refreshed its copy on 6 Nov 2026.