An interventional study of PEEP ARDSnet and PEEP LRM in ARDS, Human, Lung Injury, Acute and Respiratory Distress Syndrome, sponsored by Massachusetts General Hospital. Terminated at 1 site in United States. Open to participants aged 18 Years to 85 Years. Per ClinicalTrials.gov, last updated 2025-12-19.
Sponsored by Massachusetts General Hospital · Not applicable, Interventional, and Treatment
The goal of this interventional crossover study, in intubated and mechanically ventilated Acute Respiratory Distress Syndrome (ARDS) patients, is to compare two positive end-expiratory pressure (PEEP) titration techniques regarding: respiratory mechanics, gas exchange, changes in aeration, ventilation/perfusion matching its impact on cardiac function, especially the right heart (RH). The PEEP titration techniques are: PEEP selection based on low PEEP/high FiO2 table ("PEEPARDSnet") and lung recruitment maneuver (LRM) plus PEEPdec titration based on the best compliance of the respiratory system("PEEPLRM").
A recent large observational study published on JAMA showed that Acute Respiratory Distress Syndrome (ARDS) is associated with high mortality and developed in 10.4% of 29,144 patients admitted to the intensive care unit from 50 countries across 5 continents. Mechanical ventilation is the cornerstone for lung treatment during ARDS. Lung protective ventilation improved ARDS outcome significantly. However, it is still unclear what method should be used to select levels of positive end-expiratory pressure (PEEP).
In the current study proposal, the investigators hypothesized that, when ARDS lungs are recruitable, a lung recruitment maneuver (LRM) and PEEP titration ("PEEPLRM") improve ventilation/perfusion matching and decreased right heart workload when compared to the actual standard of care PEEP selection based on low PEEP/high FiO2 table ("PEEPARDSnet").
The investigators will test this hypothesis in an interventional crossover study.
50 patients with ARDS will be enrolled in a physiological and lung and heart imaging study.
The protocol is divided in the following phases:
A) "PEEPARDSnet": setting PEEP according to the ARDSnet table (low PEEP/ high FiO2)
B) Recruitability assessment sequence:
P-V curve tool (Hamilton ventilator): evaluate patient recruitability, among three criteria, two must be positive to consider a subject recruitable: (1) Presence of a lower inflection point (2) Linear compliance measured more than 2 times higher than the dynamic compliance (3) Increase in volume of more than 300mL during the descendant limb of the PV curve at a same given pressure (20 cmH2O)(Hysteresis property).
C)"PEEPLRM": LRM plus PEEP decremental trial guided by best compliance. Lung and heart response to "PEEPLRM": we will compare the driving pressure (DP) value (DP = Plateau pressure - PEEP) and transthoracic echocardiography (TTE) with the values at PEEPARDSnet. In the advent of an increased DP and/or new onset of abnormal values at the TTE, we will resume the PEEPARDSnet settings during the 48h follow-up phase.
Before and after the lung recruitment maneuver and decremental PEEP trial, we will collect:
Follow-up phase:
In 24 and 48 hours, if the subject did not present a negative response to "PEEPLRM" as described above , we will repeat the recruitment maneuver and the decremental PEEP trial and and we will collect:
before and after the aforementioned intervention.
Exclusion Criteria:
There is no randomization in this interventional, crossover, physiological study. All participants will receive the same procedures in the same order. The investigators will compare two PEEPs ("PEEPARDSnet" vs. "PEEPLRM"). Interventions: 1. PEEP ARDSnet: we will select the PEEP based on low PEEP/high FiO2 table (ARDSnet). 2. PEEP LRM: we will perform a lung recruitment maneuver (LRM) and select PEEP based on transpulmonary pressure.
Procedure: PEEP ARDSnet · Procedure: PEEP LRM
PEEP settings based on the low PEEP/high FiO2 table
A lung recruitment maneuver (LRM) followed by PEEP guided by transpulmonary pressure.
Driving Pressure (cmH2O)
The primary endpoint of this study is to describe the airways driving pressures (defined as Plateau Pressure minus PEEP) during "PEEP ARDSnet" and "PEEP LRM".
Time frame: 1h (Phase A: "PEEP ARDSnet") and 2h (Phase C: "PEEP LRM") after the beginning of the study procedures
Chest wall and lung elastances (cmH2O/L)
This exploratory outcome represents the respiratory system elastance. The respiratory system elastance (ERS = EL + ECW) is the sum of lung elastance (EL) and chest wall (ECW) elastance. In order to measure ERS, we will need airway pressure (measured by connecting the endotracheal tube with a pressure transducer) and pleural pressure (measured by placing an esophageal balloon connected to a pressure transducer, the esophageal pressure is a surrogate of the pleural pressure).
Time frame: 1h (Phase A: "PEEP ARDSnet"), 2h (Phase C: "PEEP LRM"), 24h and 48h after the beginning of the study procedures
Dead space (%)
This exploratory outcome is the volume (as a percent) of a breath that does not participate in gas exchange.The measure will be made using infrared absorption technology by a mainstream analyzer positioned distally to the Y piece and connected to a capnogram.
Time frame: 1h (Phase A: "PEEP ARDSnet"), 2h (Phase C: "PEEP LRM"), 24h and 48h after the beginning of the study procedures
Right heart function (Transthoracic Echocardiography)
Exploratory outcome
Time frame: 1h (Phase A: "PEEP ARDSnet"), 2h (Phase C: "PEEP LRM"), 24h and 48h after the beginning of the study procedures
Gas distribution, gas content, end-expiratory lung volume (using Electrical Impedance Tomography)
Exploratory outcome
Time frame: 1h (Phase A: "PEEP ARDSnet"), 2h (Phase C: "PEEP LRM"), 24h and 48h after the beginning of the study procedures
Ventilation/perfusion matching (using Electrical Impedance Tomography)
Exploratory outcome
Time frame: 1h (Phase A: "PEEP ARDSnet"), 2h (Phase C: "PEEP LRM"), 24h and 48h after the beginning of the study procedures
Blood arterial and central venous pressures
Exploratory outcome
Time frame: 1h (Phase A: "PEEP ARDSnet"), 2h (Phase C: "PEEP LRM"), 24h and 48h after the beginning of the study procedures
Days free of mechanical ventilation
Exploratory outcome
Time frame: 28 days
ICU length of stay
Exploratory outcome
Time frame: 28 days
Hospital length of stay
Exploratory outcome
Time frame: 28 days
Mortality
Exploratory outcome
Time frame: 28 days
Plan to share: No
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Respiratory Distress Syndrome→
Massachusetts General Hospital