HemodynamIc eFfects of Lung Collapse and overdIstension During ARDS (HI-FIVE)

February 14, 2026 updated by: GRIECO DOMENICO LUCA, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Italy
    • Rome
      • Rome, Rome, Italy, 00168
        • Fondazione Policlinico Universitario A.Gemelli IRCCS
        • Sub-Investigator:
          • Filippo Bongiovanni, MD
        • Contact:
        • Principal Investigator:
          • Massimo Antonelli, MD
        • Sub-Investigator:
          • Tommaso Rosà, MD
        • Sub-Investigator:
          • Antonio Maria Dell'Anna, MD
        • Sub-Investigator:
          • Simone Carelli, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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;

Exclusion Criteria:

  • 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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Lung collapse and overdistention crossing point PEEP
Other: Change in PEEP
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
Experimental: Low lung collapse PEEP
Other: Change in PEEP
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
Experimental: Low lung overdistention PEEP
Other: Change in PEEP
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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)
Assesment performed at the end of each of the three 30 minute steps
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
Assesment performed at the end of each of the three 30 minute steps
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)
Assesment performed at the end of each of the three 30 minute steps
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
Assesment performed at the end of each of the three 30 minute steps

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
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)
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
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)
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
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 %)
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
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 %)
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
The relationship between transpulmonary pressure variations (cmH2O) and central venous pressure variations (cmH2O) between PEEP levels will be assessed through Pearson correlations
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 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
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
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)
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
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)
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
The effects of PEEP cardiac output (L/min) will be correlated through Pearson correlations with the individual PEEP-induced changes in lung volume (mL)
Assesment performed at the end of each of the three 30 minute steps

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Domenico Luca Grieco, MD, Fondazione Policlinico Universitario A. gemelli, IRCCS

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 28, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 28, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 7, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 14, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 20, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 20, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 14, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 7795

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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