Critical IllnessFENICE IINCT06394947
Fluid Challenge in Intensive Care The FENICE II Study
An observational study of Critical Illness and Septic Shock, run by Humanitas Clinical and Research Center at 2 sites in Italy.
Trial summary
Fluids are considered the primary treatment for critically ill patients admitted to the intensive care unit (ICU), aiming to replace losses and or to enhance venous return, stroke volume, and consequently, cardiac output and tissue oxygen delivery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Critical Illness, Septic Shock
- What is being tested?
- Fluid administration (any type)
- Type of treatment
- Injection or infusion
- How many people
- 4,734 participants
- Where
- 2 sitesItaly
- Study dates
- 1 Jan 2025to 30 Nov 2025
- How long will I take part?
- 30 Days
- Phase
- Observational
- Are there results?
- None posted in the registry
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 consecutive adult (≥18 years old) patients admitted to the intensive care unit and expected to stay at least 48h.
Who may be able to join
- All consecutive adult (≥18 years old) patients admitted to ICU and expected to stay at least 48h.
Who cannot join
- Planned admission after surgery for overnight ICU stay.
- Refusal of consent
- Moribund patients (i.e. expected survival < 24h)
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
Humanitas Research Hospital
Milan
Humanitas Clinical and Research center
Rozzano, Milan, 20089
About this study
Official title: Fluid Challenge in Intensive Care: a Worldwide Global Inception Cohort Study: The FENICE II Study
Fluids are considered the primary treatment for critically ill patients admitted to the intensive care unit (ICU), aiming to replace losses and or to enhance venous return, stroke volume, and consequently, cardiac output and tissue oxygen delivery. The modalities, volumes, and targets employed to titrate fluid therapy vary significantly in current clinical practice, as shown by the original FENICE study 10 years ago. FENICE studied how fluid challenges are given at the bedside. Very little is known about how this practice has changed since, how fluid administration (maintenance) is performed in general, and how the modality may impact outcomes. FENICE II is designed to explore these issues.
Objectives:
Read more
To provide a comprehensive global description of fluid administration modalities during the initial days of ICU admission and to explore any association between fluid administration characteristics and clinical outcomes.
To describe the fluid challenge administration modality and appraise the use of variables and functional hemodynamic tests to guide bolus infusion.
Read the detailed description
Primary aim: The primary aim is to describe the modality of fluid administration during the first 5 days of ICU stay considering 1) the overall fluid balance; 2) the characteristics of the fluids given; 3) the modality of fluid administration.
Secondary aims:
- To explore any association between fluid administration characteristics and clinical outcomes (see further)
- To evaluate factors potentially associated with the respective proportion of the different modalities of fluid administration
- To characterize FC administration modality in a large cohort of ICU patients.
Statistical Analysis:
Data will be described as median and interquartile range (IQR) or number and percentage. Categorical variables were compared using Fisher's exact test and continuous variables using the nonparametric Wilcoxon test, Mann-Whitney test, or Kruskal-Wallis test.
Volume of fluid and fluid balance (primary outcome) will be reported as median [IQR] from day 1 to day 5. This volume, fluid balance and respective volume of bolus and continuous fluid administration will be reported as distinct alluvial plots reporting median of fluid at day 1 to 5 per quartile along with outcome.
In way to assess relationship between volume of fluid received, characteristics and outcome (secondary outcome), longitudinal cluster modelling will be used to identify clusters of patients with similar patterns of fluid administration profile. Longitudinal k-mean will be used to assess change in fluid received each day from day 1 to day 3. In way to avoid misinterpretation of findings due to time dependent competing events such death or ICU discharge, this analysis will be performed on patients alive and still in the ICU at day 3. A sensitivity analysis will be performed during first 5 days on the subgroup of patients alive and not discharged during first 5 ICU-days.
In way to assess impact of fluid administration modality/strategy on outcome (secondary endpoint), factors associated with in-hospital mortality, including identified cluster of fluid administration, will be assessed using mixed logistic regression where in-hospital mortality will be event of interest. Center effect will be included as a random effect against the intercept.
For secondary outcomes, and in particular for day-30 mortality, number of days alive without vasopressors, mechanical ventilation or renal replacement therapy, will be assessed using survival analysis.
All tests will be two-sided, and P-value less than 0.05 will be considered statistically significant.
- Conditions
- Critical Illness, Septic Shock
- Being tested
- Fluid administration (any type)
- Keywords
- Fluid Therapy, Fluid Challenge, Fluid Bolus, Intensive Care, Hemodynamic Monitoring
- Medical subject headings
- Critical Illness, Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fluid administration (any type)Other
Also called Fluid Infusion, Fluid Bolus, Fluid Balance
The fluid challenge (FC) (bolus) is defined as the administration of any bolus of fluid (crystalloid or colloid) which is expected to affect pressure/flow/perfusion variables. The FC is expected to be completed within 30 min.
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite of various aspects of fluid therapy
Modality of fluid administration during ICU stay considering 1) the overall fluid balance; 2) the characteristics of the fluids given; 3) the modality of fluid administration
Measured: FIve days from ICU admission
Secondary outcomes (8)
ICU mortality
Mortality during ICU stay
Measured: Up to 30 days from ICU admission
In-hospital Mortality
Mortality during hospital stay after ICU discharge
Measured: Up to 30 days from ICU admission
Alive without any organ support
Number of calendar days between inclusion and 28 days that the patient is alive and with no requirement of cardiovascular, respiratory and renal support.
Measured: between inclusion and 30 days later
Organ Dysfunction - Lung
Time to cessation of mechanical ventilation during ICU stay [The number of calendar days between intubation / start of mechanical ventilation and extubation / liberation from mechanical ventilation] (maintained for at least 48 hours)].
Measured: between inclusion and 30 days later
Organ Dysfunction - Heart
Time to cessation of vasopressor support during ICU stay (The number of hours between enrollment and complete stopping of vasopressor support (defined as its complete interruption for at least 24 consecutive hours).
Measured: between inclusion and 30 days later
Organ Dysfunction - Renal
Variation of creatinine-based KDIGO stage. Renal function assessed according to KDIGO staging system.
Measured: between inclusion and 5 days later
Organ Dysfunction - Renal
Time to cessation of Renal Replacement during ICU stay [The number of calendar days between start of renal replacement therapy and complete liberation from renal replacement therapy (at least 48 hours for continuous replacement modalities and 5 days for intermittent ones).
Measured: between inclusion and 30 days later
Organ Dysfunction
Variation of daily SOFA score.
Measured: between inclusion and 5 days later
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2024
- Study start1 Jan 2025
- Primary completion30 Nov 2025
- Study completion30 Nov 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Critical IllnessStudies 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 4,734 participants (actual)
- Target duration
- 30 Days
Sponsor and investigators
- Lead sponsor
- Humanitas Clinical and Research Center
- Sponsor type
- University, hospital or other
- Collaborators
- European Society of Intensive Care Medicine
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06394947
- Sponsor's protocol ID
- FENICE II
- Acronym
- FENICE II
- Status last verified
- Feb 2026
- First submitted
- 15 Mar 2024
- Last updated
- 6 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Publications
Cecconi M, Hofer C, Teboul JL, Pettila V, Wilkman E, Molnar Z, Della Rocca G, Aldecoa C, Artigas A, Jog S, Sander M, Spies C, Lefrant JY, De Backer D; FENICE Investigators; ESICM Trial Group. Fluid challenges in intensive care: the FENICE study: A global inception cohort study. Intensive Care Med. 2015 Sep;41(9):1529-37. doi: 10.1007/s00134-015-3850-x. Epub 2015 Jul 11.
PubMed 26162676
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fluid Challenge in Intensive Care: a Worldwide Global Inception Cohort Study: The FENICE II Study
- ClinicalTrials.gov ID
- NCT06394947
- Acronym / sponsor ID
- FENICE II / FENICE II
- Conditions
- Critical Illness, Septic Shock
- Keywords
- Fluid Therapy, Fluid Challenge, Fluid Bolus, Intensive Care, Hemodynamic Monitoring
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 4,734 participants (actual)
- Lead sponsor
- Humanitas Clinical and Research CenterUniversity, hospital or other
- Collaborators
- European Society of Intensive Care Medicine
- Study start
- 1 Jan 2025 (actual)
- Primary completion
- 30 Nov 2025 (actual)
- Study completion
- 30 Nov 2025 (actual)
- First posted
- 1 May 2024 (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.
Fluids are considered the primary treatment for critically ill patients admitted to the intensive care unit (ICU), aiming to replace losses and or to enhance venous return, stroke volume, and consequently, cardiac output and tissue oxygen delivery. The modalities, volumes, and targets employed to titrate fluid therapy vary significantly in current clinical practice, as shown by the original FENICE study 10 years ago. FENICE studied how fluid challenges are given at the bedside. Very little is known about how this practice has changed since, how fluid administration (maintenance) is performed in general, and how the modality may impact outcomes. FENICE II is designed to explore these issues.
Objectives:
To provide a comprehensive global description of fluid administration modalities during the initial days of ICU admission and to explore any association between fluid administration characteristics and clinical outcomes.
To describe the fluid challenge administration modality and appraise the use of variables and functional hemodynamic tests to guide bolus infusion.
Detailed description
Primary aim: The primary aim is to describe the modality of fluid administration during the first 5 days of ICU stay considering 1) the overall fluid balance; 2) the characteristics of the fluids given; 3) the modality of fluid administration.
Secondary aims:
- To explore any association between fluid administration characteristics and clinical outcomes (see further)
- To evaluate factors potentially associated with the respective proportion of the different modalities of fluid administration
- To characterize FC administration modality in a large cohort of ICU patients.
Statistical Analysis:
Data will be described as median and interquartile range (IQR) or number and percentage. Categorical variables were compared using Fisher's exact test and continuous variables using the nonparametric Wilcoxon test, Mann-Whitney test, or Kruskal-Wallis test.
Volume of fluid and fluid balance (primary outcome) will be reported as median [IQR] from day 1 to day 5. This volume, fluid balance and respective volume of bolus and continuous fluid administration will be reported as distinct alluvial plots reporting median of fluid at day 1 to 5 per quartile along with outcome.
In way to assess relationship between volume of fluid received, characteristics and outcome (secondary outcome), longitudinal cluster modelling will be used to identify clusters of patients with similar patterns of fluid administration profile. Longitudinal k-mean will be used to assess change in fluid received each day from day 1 to day 3. In way to avoid misinterpretation of findings due to time dependent competing events such death or ICU discharge, this analysis will be performed on patients alive and still in the ICU at day 3. A sensitivity analysis will be performed during first 5 days on the subgroup of patients alive and not discharged during first 5 ICU-days.
In way to assess impact of fluid administration modality/strategy on outcome (secondary endpoint), factors associated with in-hospital mortality, including identified cluster of fluid administration, will be assessed using mixed logistic regression where in-hospital mortality will be event of interest. Center effect will be included as a random effect against the intercept.
For secondary outcomes, and in particular for day-30 mortality, number of days alive without vasopressors, mechanical ventilation or renal replacement therapy, will be assessed using survival analysis.
All tests will be two-sided, and P-value less than 0.05 will be considered statistically significant.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 30 Days
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All consecutive adult (≥18 years old) patients admitted to the intensive care unit and expected to stay at least 48h.
Key inclusion criteria (1 listed)
- All consecutive adult (≥18 years old) patients admitted to ICU and expected to stay at least 48h.
Key exclusion criteria (3 listed)
- Planned admission after surgery for overnight ICU stay.
- Refusal of consent
- Moribund patients (i.e. expected survival < 24h)
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 |
|---|---|---|
| Fluid administration (any type)Also: Fluid Infusion, Fluid Bolus, Fluid BalanceThe fluid challenge (FC) (bolus) is defined as the administration of any bolus of fluid (crystalloid or colloid) which is expected to affect pressure/flow/perfusion variables. The FC is expected to be completed within 30 min. | Other | – |
Primary outcome
Composite of various aspects of fluid therapy
Time frame: FIve days from ICU admission
Modality of fluid administration during ICU stay considering 1) the overall fluid balance; 2) the characteristics of the fluids given; 3) the modality of fluid administration
8 secondary outcomes
ICU mortality
Time frame: Up to 30 days from ICU admission
In-hospital Mortality
Time frame: Up to 30 days from ICU admission
Alive without any organ support
Time frame: between inclusion and 30 days later
Organ Dysfunction - Lung
Time frame: between inclusion and 30 days later
Organ Dysfunction - Heart
Time frame: between inclusion and 30 days later
Organ Dysfunction - Renal
Time frame: between inclusion and 5 days later
Organ Dysfunction - Renal
Time frame: between inclusion and 30 days later
Organ Dysfunction
Time frame: between inclusion and 5 days later
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2026.
- Results publication: PubMed 26162676Cecconi M, Hofer C, Teboul JL, Pettila V, Wilkman E, Molnar Z, Della Rocca G, Aldecoa C, Artigas A, Jog S, Sander M, Spies C, Lefrant JY, De Backer D; FENICE Investigators; ESICM Trial Group. Fluid challenges in intensive care: the FENICE study: A global inception cohort study. Intensive Care Med. 2015 Sep;41(9):1529-37. doi: 10.1007/s00134-015-3850-x. Epub 2015 Jul 11.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Related trials for Critical Illness
Not yet recruitingObservational study
Lactate/Albumin Ratio and Mortality in Respiratory Failure
Acute Respiratory Failure, Critical Illness
RecruitingObservational study
Respiratory Physiotherapy and Inflammatory Biomarkers in Critically Ill Patients With Pneumonia
Pneumonia, Critical Illness
Not yet recruitingObservational study
Capillary Refill Time Variation to Predict Oxygen Comsumption Variation After FLuid Challenge (CARTOFL)
Critically Ill Patients, Circulatory Shock
RecruitingPhase 4
CONTinuous Infusion Versus Intermittent Dosing of ceftaZidime/AVIbactam in Critically Ill Patients
Severe Infection
Not yet recruiting
Feasibility Study on the Use of a Walking Exoskeleton in the Intensive Care Unit
Neuromuscular Disease in Post-Intensive Care Syndrome
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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Critical Illness and Septic Shock, run by Humanitas Clinical and Research Center at 2 sites in Italy.
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 1 inclusion and 3 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: finished, as of the sponsor's last update on 6 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Composite of various aspects of fluid therapy (time frame: FIve days from ICU admission). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06394947, which also lists 1 linked publication.
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 6 Feb 2026.