ARDSHI-FIVENCT07423520
HemodynamIc eFfects of Lung Collapse and overdIstension During ARDS
A study testing Change in PEEP in people with ARDS and AHRF, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
Trial summary
The management ARDS relies on ventilatory strategies aimed at limiting ventilator-induced lung injury (VILI). The setting of PEEP is still subject of debate, as randomized clinical trials comparing standardized higher versus lower PEEP strategies failed to demonstrate a clear survival advantage. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- Change in PEEP
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteItaly
- Study dates
- 28 Feb 2026to 1 May 2027
- Phase
- Interventional
- 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
Who may be able to join
- acute respiratory failure with onset < 1 week from a predisposing risk factor, such as pneumonia, non-pulmonary infection, trauma, transfusion, aspiration, or shock;
- bilateral opacities on chest radiography and computed tomography or bilateral B lines and/or consolidations on lung ultrasound not fully explained by effusions, atelectasis, or nodules/masses;
- pulmonary edema not exclusively or primarily attributable to cardiogenic pulmonary edema/fluid overload, and hypoxemia/gas exchange abnormalities not primarily attributable to atelectasis;
- PaO2/FiO2 ratio ≤ 200 during invasive controlled mechanical ventilation;
Who cannot join
- age <18 years;
- pregnancy;
- signs of barotrauma or documented pneumothorax;
- severe tachycardia (HR > 120 bpm) and severe lacticaemia (lac > 4 mmol/L)
- pre-existing decompensated heart failure (NYHA class 3-4 and/or documented left ventricular ejection fraction < 35%);
- contraindications to EIT placing (open chest wounds, presence of cardiac pacemaker);
- intubation as a result of an acute exacerbation of chronic pulmonary disease;
- contraindications to esophageal balloon placement (high bleeding risk, esophageal varices).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site
Fondazione Policlinico Universitario A.Gemelli IRCCS
Rome, Rome, 00168
Domenico Luca Grieco, MD, +393397681623, dlgrieco@outlook.it
Massimo Antonelli, MD
About this study
Official title: HemodynamIc eFfects of Lung Collapse and overdIstension in Patients With Moderate-to-seVEre Acute Respiratory Distress Syndrome: the HI-FIVE Physiologic Study
The management ARDS relies on ventilatory strategies aimed at limiting ventilator-induced lung injury (VILI). The setting of PEEP is still subject of debate, as randomized clinical trials comparing standardized higher versus lower PEEP strategies failed to demonstrate a clear survival advantage. Only few studies explored the hemodynamic effects of various PEEP levels depending on lung recruitability. Furthermore, the role of PEEP-mediated lung collapse and overdistention on patients' hemodynamics has yet to be elucidated. In this physiologic study, the association between EIT-measured lung collapse and overdistention and cardiac function will be explored, accounting for the individual potential for lung recruitment, partitioned respiratory mechanics and cardiac preload responsiveness. Three PEEP levels will be tested in a randomized, crossover fashion: PEEP corresponding to the crossing point between lung collapse and overdistention, PEEP associated with low lung collapse, PEEP associated with low lung overdistention.
- Being tested
- Change in PEEP
- Keywords
- ARDS, AHRF, acute respiratory distress syndrome, PEEP, collapse, overdistention, hemodynamics, heart-lung interactions, mechanical ventilation, randomized crossover trial
- Medical subject headings
- Respiratory Distress Syndrome, Unconsciousness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Change in PEEPOther
Patients will undergo a decremental PEEP trial to determine the crossing-point PEEP. Secondly, three PEEP levels (low collapse PEEP, low overdistention PEEP and crossing point between lung collapse and overdistention PEEP) will be compared in a randomized order with 30-minute steps
| Study group | Role | What they receive |
|---|---|---|
| Lung collapse and overdistention crossing point PEEP | Experimental | Not described Receives: Other: Change in PEEP |
| Low lung collapse PEEP | Experimental | Not described Receives: Other: Change in PEEP |
| Low lung overdistention PEEP | Experimental | Not described Receives: Other: Change in PEEP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Impact of lung collapse on cardiac output
Evaluation of the relative contribution of lung collapse (arbitrary units) on patients' cardiac output at different PEEP levels (L/min)
Measured: Assesment performed at the end of each of the three 30 minute steps
Impact of lung collapse on pulmonary vascular resistance
Evaluation of the relative contribution of lung collapse (arbitrary units) on pulmonary vascular resistance (dyn·s/cm^5) at different PEEP levels
Measured: Assesment performed at the end of each of the three 30 minute steps
Impact of lung overdistention on cardiac output
Evaluation of the relative contribution of lung overdistention (arbitrary units) on patients' cardiac output at different PEEP levels (L/min)
Measured: Assesment performed at the end of each of the three 30 minute steps
Impact of lung overdistention on pulmonary vascular resistance
Evaluation of the relative contribution of lung overdistention (arbitrary units) on pulmonary vascular resistance (dyn·s/cm^5) at different PEEP levels
Measured: Assesment performed at the end of each of the three 30 minute steps
Secondary outcomes (9)
Correlation between potential for lung recruitment and PEEP-induced changes in cardiac output
The effects of PEEP on cardiac output (mL/min) will be correlated through Pearson correlations with the individual potential for lung recruitment, as determined by the recruitment-to-inflation ratio (R/I)
Measured: Assessment at the end of each of the three 30 minute steps
Correlation between potential for lung recruitment and PEEP-induced changes in pulmonary vascular resistance
The effects of PEEP on pulmonary vascular resistance (dyn·s/cm^5) will be correlated through Pearson correlations with the individual potential for lung recruitment, as determined by the recruitment-to-inflation ratio (R/I)
Measured: Assesment performed at the end of each of the three 30 minute steps
PEEP-induced effects on cardiac output in cardiac preload responsive vs. nonresponsive patients
The effects of PEEP on cardiac output (L/min) will be compared through subgroup comparisons (student t-test) in patients who are preload responsive and patients who are not (preload responsiveness assessed through pulse-pressure variation, expressed in %)
Measured: Assesment performed at the end of each of the three 30 minute steps
PEEP-induced effects on pulmonary vascular resistance in cardiac preload responsive vs. nonresponsive patients
The effects of PEEP on pulmonary vascular resistance (dyn·s/cm^5) will be compared through subgroup comparisons (student t-test) in patients who are preload responsive and patients who are not (preload resposnsiveness assessed through pulse-pressure variation, expressed in %)
Measured: Assesment performed at the end of each of the three 30 minute steps
Relationship between transpulmonary pressures and central venous pressure variations
The relationship between transpulmonary pressure variations (cmH2O) and central venous pressure variations (cmH2O) between PEEP levels will be assessed through Pearson correlations
Measured: At the end of each of the three 30 minute steps
Lung hysteresis
Lung hysteresis will be assessed at each of the tested PEEP levels and expressed as the area of the pressure-volume loop of the respiratory system obtained with a low-flow inflation/deflation maneuver from PEEP to a pressure of 30 cmH2O, in mL*cmH2O
Measured: At the end of each of the three 30 minute steps
Lung aeration distribution
Lung aeration distribution at each PEEP level tested will be assessed with electrical impedance tomography (EIT) and expressed as dorsal fraction of ventilation (% of total tidal volume)
Measured: At the end of each of the three 30 minute steps
Relationship between PEEP-induced changes in lung volume and PEEP-induced changes in pulmonary vascular resistance
The effects of PEEP on pulmonary vascular resistance (dyn·s/cm^5) will be correlated through Pearson correlations with the individual PEEP-induced changes in lung volume (mL)
Measured: Assesment performed at the end of each of the three 30 minute steps
Relationship between PEEP-induced changes in lung volume and PEEP-induced changes in cardiac output
The effects of PEEP cardiac output (L/min) will be correlated through Pearson correlations with the individual PEEP-induced changes in lung volume (mL)
Measured: Assesment performed at the end of each of the three 30 minute steps
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2026
- Study start28 Feb 2026 (estimated)
- Primary completion28 Feb 2027 (estimated)
- Study completion1 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ARDSStudies of the same condition, open and under way.
- More trials run by Fondazione Policlinico Universitario Agostino Gemelli IRCCSThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized crossover trial
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, GRIECO DOMENICO LUCA, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Investigators
- Domenico Luca Grieco, MD, Principal investigator, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07423520
- Sponsor's protocol ID
- 7795
- Acronym
- HI-FIVE
- Status last verified
- Feb 2026
- First submitted
- 7 Jan 2026
- Last updated
- 20 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HemodynamIc eFfects of Lung Collapse and overdIstension in Patients With Moderate-to-seVEre Acute Respiratory Distress Syndrome: the HI-FIVE Physiologic Study
- ClinicalTrials.gov ID
- NCT07423520
- Acronym / sponsor ID
- HI-FIVE / 7795
- Keywords
- ARDS, AHRF, acute respiratory distress syndrome, PEEP, collapse, overdistention, hemodynamics, heart-lung interactions
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Study start
- 28 Feb 2026 (estimated)
- Primary completion
- 28 Feb 2027 (estimated)
- Study completion
- 1 May 2027 (estimated)
- First posted
- 20 Feb 2026 (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.
The management ARDS relies on ventilatory strategies aimed at limiting ventilator-induced lung injury (VILI). The setting of PEEP is still subject of debate, as randomized clinical trials comparing standardized higher versus lower PEEP strategies failed to demonstrate a clear survival advantage. Only few studies explored the hemodynamic effects of various PEEP levels depending on lung recruitability. Furthermore, the role of PEEP-mediated lung collapse and overdistention on patients' hemodynamics has yet to be elucidated. In this physiologic study, the association between EIT-measured lung collapse and overdistention and cardiac function will be explored, accounting for the individual potential for lung recruitment, partitioned respiratory mechanics and cardiac preload responsiveness. Three PEEP levels will be tested in a randomized, crossover fashion: PEEP corresponding to the crossing point between lung collapse and overdistention, PEEP associated with low lung collapse, PEEP associated with low lung overdistention.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Randomized crossover trial
| Arm | Type | Receives |
|---|---|---|
| Lung collapse and overdistention crossing point PEEP | Experimental | Other: Change in PEEP |
| Low lung collapse PEEP | Experimental | Other: Change in PEEP |
| Low lung overdistention PEEP | Experimental | Other: Change in PEEP |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- acute respiratory failure with onset < 1 week from a predisposing risk factor, such as pneumonia, non-pulmonary infection, trauma, transfusion, aspiration, or shock;
- bilateral opacities on chest radiography and computed tomography or bilateral B lines and/or consolidations on lung ultrasound not fully explained by effusions, atelectasis, or nodules/masses;
- pulmonary edema not exclusively or primarily attributable to cardiogenic pulmonary edema/fluid overload, and hypoxemia/gas exchange abnormalities not primarily attributable to atelectasis;
- PaO2/FiO2 ratio ≤ 200 during invasive controlled mechanical ventilation;
Key exclusion criteria (8 listed)
- age <18 years;
- pregnancy;
- signs of barotrauma or documented pneumothorax;
- severe tachycardia (HR > 120 bpm) and severe lacticaemia (lac > 4 mmol/L)
- pre-existing decompensated heart failure (NYHA class 3-4 and/or documented left ventricular ejection fraction < 35%);
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 |
|---|---|---|
| Change in PEEPPatients will undergo a decremental PEEP trial to determine the crossing-point PEEP. Secondly, three PEEP levels (low collapse PEEP, low overdistention PEEP and crossing point between lung collapse and overdistention PEEP) will be compared in a randomized order with 30-minute steps | Other | Low lung collapse PEEP, Low lung overdistention PEEP, Lung collapse and overdistention crossing point PEEP |
Primary outcome
Impact of lung collapse on cardiac output
Time frame: Assesment performed at the end of each of the three 30 minute steps
Evaluation of the relative contribution of lung collapse (arbitrary units) on patients' cardiac output at different PEEP levels (L/min)
Impact of lung collapse on pulmonary vascular resistance
Time frame: Assesment performed at the end of each of the three 30 minute steps
Evaluation of the relative contribution of lung collapse (arbitrary units) on pulmonary vascular resistance (dyn·s/cm^5) at different PEEP levels
Impact of lung overdistention on cardiac output
Time frame: Assesment performed at the end of each of the three 30 minute steps
Evaluation of the relative contribution of lung overdistention (arbitrary units) on patients' cardiac output at different PEEP levels (L/min)
Impact of lung overdistention on pulmonary vascular resistance
Time frame: Assesment performed at the end of each of the three 30 minute steps
Evaluation of the relative contribution of lung overdistention (arbitrary units) on pulmonary vascular resistance (dyn·s/cm^5) at different PEEP levels
9 secondary outcomes
Correlation between potential for lung recruitment and PEEP-induced changes in cardiac output
Time frame: Assessment at the end of each of the three 30 minute steps
Correlation between potential for lung recruitment and PEEP-induced changes in pulmonary vascular resistance
Time frame: Assesment performed at the end of each of the three 30 minute steps
PEEP-induced effects on cardiac output in cardiac preload responsive vs. nonresponsive patients
Time frame: Assesment performed at the end of each of the three 30 minute steps
PEEP-induced effects on pulmonary vascular resistance in cardiac preload responsive vs. nonresponsive patients
Time frame: Assesment performed at the end of each of the three 30 minute steps
Relationship between transpulmonary pressures and central venous pressure variations
Time frame: At the end of each of the three 30 minute steps
Lung hysteresis
Time frame: At the end of each of the three 30 minute steps
Lung aeration distribution
Time frame: At the end of each of the three 30 minute steps
Relationship between PEEP-induced changes in lung volume and PEEP-induced changes in pulmonary vascular resistance
Time frame: Assesment performed at the end of each of the three 30 minute steps
Relationship between PEEP-induced changes in lung volume and PEEP-induced changes in cardiac output
Time frame: Assesment performed at the end of each of the three 30 minute steps
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 20 Feb 2026.
- Individual participant dataSharing planned: Undecided
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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.
Domenico Luca Grieco, MD principal investigator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Change in PEEP in people with ARDS and AHRF, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site 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 4 inclusion and 8 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 20 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 1 site 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?
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?
Contact Domenico Luca Grieco, MD (+393397681623, dlgrieco@outlook.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Impact of lung collapse on cardiac output (time frame: Assesment performed at the end of each of the three 30 minute steps). The study lists 4 primary outcomes in all. 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 20 Feb 2026.