Acute Respiratory Distress SyndromeRIGHTENARDSNCT05583461
Ventilator-induced Right Ventricular Injury During EIT-based PEEP Titration in Patients With ARDS
A study testing Positive end-expiratory pressure titration in people with Acute Respiratory Distress Syndrome and Right Ventricular Dysfunction, run by University of Padova at 1 site in Italy.
Trial summary
Right ventricular failure may be associated with mortality in patients with acute respiratory distress syndrome (ARDS). Mechanical ventilation may promote right ventricular failure by inducing alveolar overdistention and atelectasis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Respiratory Distress Syndrome, Right Ventricular Dysfunction
- What is being tested?
- Positive end-expiratory pressure titration
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteItaly
- Study dates
- 26 Oct 2022to 31 Dec 2025
- Phase
- Interventional
- 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
Who may be able to join
- Moderate to severe acute respiratory distress syndrome
- Inclusion within 72 hours of acute respiratory distress syndrome diagnosis
- Endotracheal intubation or tracheostomy
Who cannot join
- Age lower than 18 years old
- Pregnancy
- Absence of informed consent
- Thoracic surgery or lung transplant during the admission
- Contraindications to recruitment maneuvers (mean arterial pressure lower than 65 mmHg despite administration of fluids or vasopressors, active air leaks through a chest tube, pneumothorax or subcutaneous or mediastinal emphysema in absence of chest drainage)
- Contraindications to electrical impedance tomography (contraindication to recruitment maneuvers, presence of pacemakers or other electronic devices in the chest, injuries or burns in the electrode placement area)
- ACEP quality < 4
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Ventilator-induced Right Ventricular Injury During Electrical Impedance Tomography-based Positive End-expiratory Pressure Titration in Patients With Acute Respiratory Distress Syndrome: a Pilot Physiological Study.
Right ventricular failure may be associated with mortality in patients with acute respiratory distress syndrome (ARDS). Mechanical ventilation may promote right ventricular failure by inducing alveolar overdistention and atelectasis. Electrical impedance tomography (EIT) is a bedside non-invasive technique assessing the regional distribution of lung ventilation, thus helping titrating positive end-expiratory pressure (PEEP) to target the minimum levels of alveolar overdistension and atelectasis. The aim of this physiologic randomized crossover trial is to assess right ventricular size and function with transthoracic echocardiography with different levels of PEEP in adult patients with moderate-to-severe ARDS undergoing controlled invasive mechanical ventilation: the level of PEEP determined according to the ARDS Network low PEEP-FiO2 table, the PEEP value that minimizes the risk of alveolar overdistension and atelectasis (as determined by EIT), the highest PEEP value minimizing the risk of alveolar overdistension (as determined by EIT), and the lowest PEEP level that minimizes the risk of alveolar atelectasis (as determined by EIT). Our findings may offer valuable insights into the level of PEEP favoring right ventricular protection during mechanical ventilation in patients with ARDS.
Read the detailed description
Acute respiratory distress syndrome (ARDS) is a diffuse pulmonary inflammatory disease with multifactorial etiology that is very common in patients admitted to the intensive care unit (ICU) and is associated with unsatisfactory short- and long-term prognosis. Patients with ARDS can develop right ventricular (RV) failure, which occurs in 22-50% of patients despite lung protective ventilation and is associated with increased mortality. Despite being required to ensure survival of patients with ARDS, mechanical ventilation itself may have injurious effects on RV function. First, high transpulmonary pressure, secondary to the use of high tidal volume, plateau pressure or positive end-expiratory pressure (PEEP), can cause alveolar overdistension, especially in the aerated parenchymal regions, and collapse of alveolar vessels. The consequent increase in pulmonary arterial pressure may lead to excessively high RV afterload and reduced systolic function. Second, the development of parenchymal atelectasis potentially secondary to the application of low tidal volumes and/or PEEP may increase pulmonary vascular resistance because of extra-alveolar vascular collapse. Finally, mechanical ventilation can have indirect effects on pulmonary circulation and RV function, mediated by alveolar oxygenation, acidosis, and hypercapnia.
The application of PEEP can prevent cyclic opening and closing of the alveoli (i.e., atelectrauma) and improve oxygenation. Ideally, PEEP should maintain lung recruitment and optimize oxygenation and dead space, while at the same time avoiding alveolar overdistension and hemodynamic complications. However, the PEEP titration strategy in patients with ARDS is still widely debated, due to the variability of the effects of PEEP in different patients and different lung parenchymal regions in the same patient. Depending on the extent of potentially recruitable lung parenchyma and the distribution of lung damage, the application of PEEP can cause alveolar overdistension and promote RV failure and/or favor alveolar recruitment and improve RV function. Therefore, it is stil unclear what level of PEEP is associated with the optimization of RV function in patients with ARDS. We may hypothesize that the level of PEEP able to reduce alveolar collapse without increasing overdistension may improve RV function.
Several strategies have been suggested to assess lung recruitability and PEEP responsiveness in patients with ARDS. Electrical impedance tomography (EIT) is a bedside non-invasive technique that monitors the regional distribution of lung ventilation. The choice of the PEEP value that minimizes the extent of overdistension and atelectasis, as assessed with EIT, was associated with better respiratory mechanics and survival in patients with severe ARDS in some pilot studies.
The aim of this prospective pathophysiological interventional study is to evaluate the variation of RV size and function with transthoracic echocardiography in adult patients requiring invasive controlled mechanical ventilation for moderate-to-severe ARDS with four different PEEP values applied according to a randomized sequence in each patient:
- The level of PEEP determined according to the ARDS Network low PEEP-fraction of inspired oxygen (FiO2) table;
- The PEEP value that minimizes the risk of overdistension and atelectasis, as determined by EIT;
- The highest PEEP value that minimizes the risk of overdistension, as determined by EIT;
- The lowest PEEP level that minimizes the risk of atelectasis, as determined by EIT.
The primary hypothesis of the study is that the level of PEEP that simultaneously minimizes alveolar overdistension and collapse is associated with better RV function than the PEEP level selected based on the low PEEP-FiO2 table and PEEP levels that minimize overdistension and collapse, separately. The secondary hypotheses of the study are that: 1) the level of PEEP that minimizes overdistension is associated with better RV function than the level of PEEP that minimizes collapse; 2) the PEEP level that minimizes alveolar collapse is associated with greater pulmonary air content, as assessed by lung ultrasound, compared to the PEEP levels chosen based on the low PEEP-FiO2 table, the PEEP level that minimizes overdistension and collapse simultaneously, and the PEEP level that minimizes overdistension.
The physiological data obtained from this study may offer valuable insights into the right ventricular-protective level of PEEP in patients with ARDS and support future large randomized studies investigating PEEP levels associated with improved patient survival.
- Being tested
- Positive end-expiratory pressure titration
- Keywords
- Acute respiratory distress syndrome, Mechanical ventilation, Right ventricular dysfunction, Positive end-expiratory pressure, Electrical impedance tomography, Echocardiography
- Medical subject headings
- Respiratory Distress Syndrome, Ventricular Dysfunction, Right
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Positive end-expiratory pressure titrationProcedure or surgery
Positive end-expiratory pressure level
| Study group | Role | What they receive |
|---|---|---|
| PEEP level according to the low PEEP-FiO2 table | Experimental | Positive end-expiratory pressure (PEEP) level selected based on patient's fraction of inspired oxygen (FiO2) according to the low PEEP-FiO2 table proposed by the Acute Respiratory Distress Syndrome Network Guidelines Receives: Procedure: Positive end-expiratory pressure titration |
| PEEP minimizing the risk of overdistension and atelectasis | Experimental | Positive end-expiratory pressure (PEEP) level selected based on the intersection between the curves of the cumulative percentages of compliance loss due to alveolar overdistension and atelectasis, respectively, as assessed with an electrical impedance tomography-based decremental PEEP trial Receives: Procedure: Positive end-expiratory pressure titration |
| PEEP minimizing the risk of overdistension | Experimental | Highest positive end-expiratory pressure (PEEP) level associated with no alveolar overdistention selected based on the curve of the cumulative percentage of compliance loss due to alveolar overdistension, as assessed with an electrical impedance tomography-based decremental PEEP trial Receives: Procedure: Positive end-expiratory pressure titration |
| PEEP minimizing the risk of atelectasis | Experimental | Lowest positive end-expiratory pressure (PEEP) level associated with no alveolar collapse selected based on the curve of the cumulative percentage of compliance loss due to alveolar collapse, as assessed with an electrical impedance tomography-based decremental PEEP trial Receives: Procedure: Positive end-expiratory pressure titration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Right ventricle diameter 1
Maximal transversal dimension in the basal one third of right ventricular inflow at end-diastole in the right ventricle-focused apical four-chamber view
Measured: Measured after 20 minutes from the application of each of the four levels of PEEP
Right ventricle diameter 2
Transversal right ventricular diameter in the middle third of right ventricular inflow, approximately halfway between the maximal basal diameter and the apex, at the level of papillary muscles at end-diastole.
Measured: Measured after 20 minutes from the application of each of the four levels of PEEP
Right ventricle fractional area change
Ratio of the difference between end-diastolic area and end-systolic area to end-diastolic area, which are determined after manual tracing of right ventricular endocardial border from the lateral tricuspid annulus along the free wall to the apex and back to medial tricuspid annulus, along the interventricular septum at end-diastole and at end-systole, in the right ventricle-focused apical four-chamber view
Measured: Measured after 20 minutes from the application of each of the four levels of PEEP
Eccentricity index
Ratio between two left ventricular axes, one parallel to the interventricular septum and one perpendicular to this, in the mid-papillary parasternal short axis view
Measured: Measured after 20 minutes from the application of each of the four levels of PEEP
Tricuspid annular plane systolic excursion
Tricuspid annular longitudinal excursion by M-mode, measured between end-diastole and peak systole in the apical four-chamber view that achieves parallel alignment of Doppler beam with right ventricular free wall longitudinal excursion
Measured: Measured after 20 minutes from the application of each of the four levels of PEEP
Systolic velocity of the lateral tricuspid annulus derived from tissue Doppler imaging
Peak systolic velocity of lateral tricuspid annulus by pulsed-wave tissue Doppler imaging in the apical four-chamber view that achieves parallel alignment of Doppler beam with right ventricular free wall longitudinal excursion
Measured: Measured after 20 minutes from the application of each of the four levels of PEEP
Right ventricular index of myocardial performance
The ratio of the sum between isovolumic contraction and relaxation times to ejection time measured by pulsed-wave tissue Doppler imaging in the apical four-chamber view that achieves parallel alignment of Doppler beam with right ventricular free wall longitudinal excursion
Measured: Measured after 20 minutes from the application of each of the four levels of PEEP
Right ventricle systolic pressure
Calculated from the velocity of tricuspid regurgitation jet, measured in the view allowing the highest value, by applying simplified Bernoulli equation and adding right atrial pressure estimated from central venous pressure
Measured: Measured after 20 minutes from the application of each of the four levels of PEEP
Myocardial isovolumic acceleration
Ratio of lateral tricuspid annulus peak velocity during isovolumic contraction to acceleration time by pulsed-wave tissue Doppler imaging in the apical four-chamber view that achieves parallel alignment of Doppler beam with right ventricular free wall longitudinal excursion
Measured: Measured after 20 minutes from the application of each of the four levels of PEEP
Right ventricle stroke index
Ratio of right ventricular stroke volume, calculated as product between velocity-time integral at the level of pulmonary valve and transverse area of right ventricular outflow tract in the aortic valve-level parasternal short axis view during systole, and body surface area
Measured: Measured after 20 minutes from the application of each of the four levels of PEEP
Right ventricle stroke work index
Product between right ventricle stroke index and right ventricle systolic pressure
Measured: Measured after 20 minutes from the application of each of the four levels of PEEP
Right ventricular free wall longitudinal strain
Peak value of longitudinal speckle-tracking-derived strain, averaged over the three segments of the right ventricular free wall, after manual tracing of right ventricular endocardial border from the lateral tricuspid annulus along the free wall to the apex and back to medial tricuspid annulus in right ventricle-focused apical four-chamber view
Measured: Measured after 20 minutes from the application of each of the four levels of PEEP
Secondary outcomes (10)
Ventilator settings
Tidal volume, respiratory rate, fraction of inspired oxygen, inspiratory to expiratory time
Measured: Measured after 20 minutes from the application of each of the four levels of PEEP
Respiratory mechanics
Plateau pressure, total positive end-expiratory pressure, driving pressure, mechanical power
Measured: Measured after 20 minutes from the application of each of the four levels of PEEP
Arterial blood gas analysis
pH, arterial partial pressure of carbon dioxide, arterial partial pressure of oxygen, arterial oxygen saturation, bicarbonate, lactate
Measured: Measured after 20 minutes from the application of each of the four levels of PEEP
Dead space
Estimated from the Bohr-Enghoff equation (ratio of the difference between arterial partial pressure of carbon dioxide and end-tidal carbon dioxide to arterial partial pressure of carbon dioxide)
Measured: Measured after 20 minutes from the application of each of the four levels of PEEP
Ventilatory ratio
Product between minute ventilation and arterial partial pressure of carbon dioxide, divided by predicted body weight x 100 x 37.5
Measured: Measured after 20 minutes from the application of each of the four levels of PEEP
Shunt
Calculated as (1 - arterial oxygen saturation) divided by (1 - central venous oxygen saturation)
Measured: Measured after 20 minutes from the application of the intervention
Hemodynamics
Systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, central venous pressure, dosage of vasoactive agents
Measured: Measured after 20 minutes from the application of the intervention
Pleural and lung ultrasound
Lung ultrasound score, lung reaeration score
Measured: Measured after 20 minutes from the application of the intervention
Renal ultrasound
Renal resistive index, renal venous stasis index
Measured: Measured after 20 minutes from the application of the intervention
Ultrasound image quality
Quality assessed according to the 2018 American College of Emergency Physicians Guidelines
Measured: Measured after 20 minutes from the application of the intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2022
- Study start26 Oct 2022
- Primary completion31 Dec 2025
- Study completion31 Dec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (43)Papers the sponsor has linked to this study.
- Other trials for Acute Respiratory Distress SyndromeStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized sequence of application of four levels of positive end-expiratory pressure in adult patients requiring invasive controlled mechanical ventilation for acute respiratory distress syndrome
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Padova
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tommaso Pettenuzzo, University of Padova
- Investigators
- Tommaso Pettenuzzo, MD, Principal investigator, Institute of Anesthesiology and Intensive Care, Padova University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05583461
- Sponsor's protocol ID
- 5546/AO/22
- Acronym
- RIGHTENARDS
- Status last verified
- May 2026
- First submitted
- 13 Oct 2022
- Last updated
- 7 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Fan E, Brodie D, Slutsky AS. Acute Respiratory Distress Syndrome: Advances in Diagnosis and Treatment. JAMA. 2018 Feb 20;319(7):698-710. doi: 10.1001/jama.2017.21907.
PubMed 29466596ARDS Definition Task Force; Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669.
PubMed 22797452Gattinoni L, Marini JJ, Pesenti A, Quintel M, Mancebo J, Brochard L. The "baby lung" became an adult. Intensive Care Med. 2016 May;42(5):663-673. doi: 10.1007/s00134-015-4200-8. Epub 2016 Jan 18.
PubMed 26781952Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291.
PubMed 26903337Bein T, Grasso S, Moerer O, Quintel M, Guerin C, Deja M, Brondani A, Mehta S. The standard of care of patients with ARDS: ventilatory settings and rescue therapies for refractory hypoxemia. Intensive Care Med. 2016 May;42(5):699-711. doi: 10.1007/s00134-016-4325-4. Epub 2016 Apr 4.
PubMed 27040102Herridge MS, Tansey CM, Matte A, Tomlinson G, Diaz-Granados N, Cooper A, Guest CB, Mazer CD, Mehta S, Stewart TE, Kudlow P, Cook D, Slutsky AS, Cheung AM; Canadian Critical Care Trials Group. Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med. 2011 Apr 7;364(14):1293-304. doi: 10.1056/NEJMoa1011802.
PubMed 21470008Acute Respiratory Distress Syndrome Network; Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8. doi: 10.1056/NEJM200005043421801.
PubMed 10793162Guerin C, Reignier J, Richard JC, Beuret P, Gacouin A, Boulain T, Mercier E, Badet M, Mercat A, Baudin O, Clavel M, Chatellier D, Jaber S, Rosselli S, Mancebo J, Sirodot M, Hilbert G, Bengler C, Richecoeur J, Gainnier M, Bayle F, Bourdin G, Leray V, Girard R, Baboi L, Ayzac L; PROSEVA Study Group. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013 Jun 6;368(23):2159-68. doi: 10.1056/NEJMoa1214103. Epub 2013 May 20.
PubMed 23688302Papazian L, Forel JM, Gacouin A, Penot-Ragon C, Perrin G, Loundou A, Jaber S, Arnal JM, Perez D, Seghboyan JM, Constantin JM, Courant P, Lefrant JY, Guerin C, Prat G, Morange S, Roch A; ACURASYS Study Investigators. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010 Sep 16;363(12):1107-16. doi: 10.1056/NEJMoa1005372.
PubMed 20843245Tremblay LN, Slutsky AS. Ventilator-induced lung injury: from the bench to the bedside. Intensive Care Med. 2006 Jan;32(1):24-33. doi: 10.1007/s00134-005-2817-8. Epub 2005 Oct 18. No abstract available.
PubMed 16231069Kuipers MT, van der Poll T, Schultz MJ, Wieland CW. Bench-to-bedside review: Damage-associated molecular patterns in the onset of ventilator-induced lung injury. Crit Care. 2011;15(6):235. doi: 10.1186/cc10437. Epub 2011 Nov 30.
PubMed 22216838Slutsky AS, Ranieri VM. Ventilator-induced lung injury. N Engl J Med. 2013 Nov 28;369(22):2126-36. doi: 10.1056/NEJMra1208707. No abstract available.
PubMed 24283226Del Sorbo L, Slutsky AS. Acute respiratory distress syndrome and multiple organ failure. Curr Opin Crit Care. 2011 Feb;17(1):1-6. doi: 10.1097/MCC.0b013e3283427295.
PubMed 21157315Cressoni M, Cadringher P, Chiurazzi C, Amini M, Gallazzi E, Marino A, Brioni M, Carlesso E, Chiumello D, Quintel M, Bugedo G, Gattinoni L. Lung inhomogeneity in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 2014 Jan 15;189(2):149-58. doi: 10.1164/rccm.201308-1567OC.
PubMed 24261322Yoshida T, Fujino Y, Amato MB, Kavanagh BP. Fifty Years of Research in ARDS. Spontaneous Breathing during Mechanical Ventilation. Risks, Mechanisms, and Management. Am J Respir Crit Care Med. 2017 Apr 15;195(8):985-992. doi: 10.1164/rccm.201604-0748CP.
PubMed 27786562
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ventilator-induced Right Ventricular Injury During Electrical Impedance Tomography-based Positive End-expiratory Pressure Titration in Patients With Acute Respiratory Distress Syndrome: a Pilot Physiological Study.
- ClinicalTrials.gov ID
- NCT05583461
- Acronym / sponsor ID
- RIGHTENARDS / 5546/AO/22
- Keywords
- Acute respiratory distress syndrome, Mechanical ventilation, Right ventricular dysfunction, Positive end-expiratory pressure, Electrical impedance tomography, Echocardiography
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of PadovaUniversity, hospital or other
- Study start
- 26 Oct 2022 (actual)
- Primary completion
- 31 Dec 2025 (actual)
- Study completion
- 31 Dec 2025 (actual)
- First posted
- 17 Oct 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.
Right ventricular failure may be associated with mortality in patients with acute respiratory distress syndrome (ARDS). Mechanical ventilation may promote right ventricular failure by inducing alveolar overdistention and atelectasis. Electrical impedance tomography (EIT) is a bedside non-invasive technique assessing the regional distribution of lung ventilation, thus helping titrating positive end-expiratory pressure (PEEP) to target the minimum levels of alveolar overdistension and atelectasis. The aim of this physiologic randomized crossover trial is to assess right ventricular size and function with transthoracic echocardiography with different levels of PEEP in adult patients with moderate-to-severe ARDS undergoing controlled invasive mechanical ventilation: the level of PEEP determined according to the ARDS Network low PEEP-FiO2 table, the PEEP value that minimizes the risk of alveolar overdistension and atelectasis (as determined by EIT), the highest PEEP value minimizing the risk of alveolar overdistension (as determined by EIT), and the lowest PEEP level that minimizes the risk of alveolar atelectasis (as determined by EIT). Our findings may offer valuable insights into the level of PEEP favoring right ventricular protection during mechanical ventilation in patients with ARDS.
Detailed description
Acute respiratory distress syndrome (ARDS) is a diffuse pulmonary inflammatory disease with multifactorial etiology that is very common in patients admitted to the intensive care unit (ICU) and is associated with unsatisfactory short- and long-term prognosis. Patients with ARDS can develop right ventricular (RV) failure, which occurs in 22-50% of patients despite lung protective ventilation and is associated with increased mortality. Despite being required to ensure survival of patients with ARDS, mechanical ventilation itself may have injurious effects on RV function. First, high transpulmonary pressure, secondary to the use of high tidal volume, plateau pressure or positive end-expiratory pressure (PEEP), can cause alveolar overdistension, especially in the aerated parenchymal regions, and collapse of alveolar vessels. The consequent increase in pulmonary arterial pressure may lead to excessively high RV afterload and reduced systolic function. Second, the development of parenchymal atelectasis potentially secondary to the application of low tidal volumes and/or PEEP may increase pulmonary vascular resistance because of extra-alveolar vascular collapse. Finally, mechanical ventilation can have indirect effects on pulmonary circulation and RV function, mediated by alveolar oxygenation, acidosis, and hypercapnia.
The application of PEEP can prevent cyclic opening and closing of the alveoli (i.e., atelectrauma) and improve oxygenation. Ideally, PEEP should maintain lung recruitment and optimize oxygenation and dead space, while at the same time avoiding alveolar overdistension and hemodynamic complications. However, the PEEP titration strategy in patients with ARDS is still widely debated, due to the variability of the effects of PEEP in different patients and different lung parenchymal regions in the same patient. Depending on the extent of potentially recruitable lung parenchyma and the distribution of lung damage, the application of PEEP can cause alveolar overdistension and promote RV failure and/or favor alveolar recruitment and improve RV function. Therefore, it is stil unclear what level of PEEP is associated with the optimization of RV function in patients with ARDS. We may hypothesize that the level of PEEP able to reduce alveolar collapse without increasing overdistension may improve RV function.
Several strategies have been suggested to assess lung recruitability and PEEP responsiveness in patients with ARDS. Electrical impedance tomography (EIT) is a bedside non-invasive technique that monitors the regional distribution of lung ventilation. The choice of the PEEP value that minimizes the extent of overdistension and atelectasis, as assessed with EIT, was associated with better respiratory mechanics and survival in patients with severe ARDS in some pilot studies.
The aim of this prospective pathophysiological interventional study is to evaluate the variation of RV size and function with transthoracic echocardiography in adult patients requiring invasive controlled mechanical ventilation for moderate-to-severe ARDS with four different PEEP values applied according to a randomized sequence in each patient:
- The level of PEEP determined according to the ARDS Network low PEEP-fraction of inspired oxygen (FiO2) table;
- The PEEP value that minimizes the risk of overdistension and atelectasis, as determined by EIT;
- The highest PEEP value that minimizes the risk of overdistension, as determined by EIT;
- The lowest PEEP level that minimizes the risk of atelectasis, as determined by EIT.
The primary hypothesis of the study is that the level of PEEP that simultaneously minimizes alveolar overdistension and collapse is associated with better RV function than the PEEP level selected based on the low PEEP-FiO2 table and PEEP levels that minimize overdistension and collapse, separately. The secondary hypotheses of the study are that: 1) the level of PEEP that minimizes overdistension is associated with better RV function than the level of PEEP that minimizes collapse; 2) the PEEP level that minimizes alveolar collapse is associated with greater pulmonary air content, as assessed by lung ultrasound, compared to the PEEP levels chosen based on the low PEEP-FiO2 table, the PEEP level that minimizes overdistension and collapse simultaneously, and the PEEP level that minimizes overdistension.
The physiological data obtained from this study may offer valuable insights into the right ventricular-protective level of PEEP in patients with ARDS and support future large randomized studies investigating PEEP levels associated with improved patient survival.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Randomized sequence of application of four levels of positive end-expiratory pressure in adult patients requiring invasive controlled mechanical ventilation for acute respiratory distress syndrome
| Arm | Type | Receives |
|---|---|---|
| PEEP level according to the low PEEP-FiO2 table | Experimental | Procedure: Positive end-expiratory pressure titrationPositive end-expiratory pressure (PEEP) level selected based on patient's fraction of inspired oxygen (FiO2) according to the low PEEP-FiO2 table proposed by the Acute Respiratory Distress Syndrome Network Guidelines |
| PEEP minimizing the risk of overdistension and atelectasis | Experimental | Procedure: Positive end-expiratory pressure titrationPositive end-expiratory pressure (PEEP) level selected based on the intersection between the curves of the cumulative percentages of compliance loss due to alveolar overdistension and atelectasis, respectively, as assessed with an electrical impedance tomography-based decremental PEEP trial |
| PEEP minimizing the risk of overdistension | Experimental | Procedure: Positive end-expiratory pressure titrationHighest positive end-expiratory pressure (PEEP) level associated with no alveolar overdistention selected based on the curve of the cumulative percentage of compliance loss due to alveolar overdistension, as assessed with an electrical impedance tomography-based decremental PEEP trial |
| PEEP minimizing the risk of atelectasis | Experimental | Procedure: Positive end-expiratory pressure titrationLowest positive end-expiratory pressure (PEEP) level associated with no alveolar collapse selected based on the curve of the cumulative percentage of compliance loss due to alveolar collapse, as assessed with an electrical impedance tomography-based decremental PEEP trial |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Moderate to severe acute respiratory distress syndrome
- Inclusion within 72 hours of acute respiratory distress syndrome diagnosis
- Endotracheal intubation or tracheostomy
Key exclusion criteria (7 listed)
- Age lower than 18 years old
- Pregnancy
- Absence of informed consent
- Thoracic surgery or lung transplant during the admission
- Contraindications to recruitment maneuvers (mean arterial pressure lower than 65 mmHg despite administration of fluids or vasopressors, active air leaks through a chest tube, pneumothorax or subcutaneous or mediastinal emphysema in absence of chest drainage)
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 |
|---|---|---|
| Positive end-expiratory pressure titrationPositive end-expiratory pressure level | Procedure or surgery | PEEP level according to the low PEEP-FiO2 table, PEEP minimizing the risk of atelectasis, PEEP minimizing the risk of overdistension, PEEP minimizing the risk of overdistension and atelectasis |
Primary outcome
Right ventricle diameter 1
Time frame: Measured after 20 minutes from the application of each of the four levels of PEEP
Maximal transversal dimension in the basal one third of right ventricular inflow at end-diastole in the right ventricle-focused apical four-chamber view
Right ventricle diameter 2
Time frame: Measured after 20 minutes from the application of each of the four levels of PEEP
Transversal right ventricular diameter in the middle third of right ventricular inflow, approximately halfway between the maximal basal diameter and the apex, at the level of papillary muscles at end-diastole.
Right ventricle fractional area change
Time frame: Measured after 20 minutes from the application of each of the four levels of PEEP
Ratio of the difference between end-diastolic area and end-systolic area to end-diastolic area, which are determined after manual tracing of right ventricular endocardial border from the lateral tricuspid annulus along the free wall to the apex and back to medial tricuspid annulus, along the interventricular septum at end-diastole and at end-systole, in the right ventricle-focused apical four-chamber view
Eccentricity index
Time frame: Measured after 20 minutes from the application of each of the four levels of PEEP
Ratio between two left ventricular axes, one parallel to the interventricular septum and one perpendicular to this, in the mid-papillary parasternal short axis view
Tricuspid annular plane systolic excursion
Time frame: Measured after 20 minutes from the application of each of the four levels of PEEP
Tricuspid annular longitudinal excursion by M-mode, measured between end-diastole and peak systole in the apical four-chamber view that achieves parallel alignment of Doppler beam with right ventricular free wall longitudinal excursion
Systolic velocity of the lateral tricuspid annulus derived from tissue Doppler imaging
Time frame: Measured after 20 minutes from the application of each of the four levels of PEEP
Peak systolic velocity of lateral tricuspid annulus by pulsed-wave tissue Doppler imaging in the apical four-chamber view that achieves parallel alignment of Doppler beam with right ventricular free wall longitudinal excursion
Right ventricular index of myocardial performance
Time frame: Measured after 20 minutes from the application of each of the four levels of PEEP
The ratio of the sum between isovolumic contraction and relaxation times to ejection time measured by pulsed-wave tissue Doppler imaging in the apical four-chamber view that achieves parallel alignment of Doppler beam with right ventricular free wall longitudinal excursion
Right ventricle systolic pressure
Time frame: Measured after 20 minutes from the application of each of the four levels of PEEP
Calculated from the velocity of tricuspid regurgitation jet, measured in the view allowing the highest value, by applying simplified Bernoulli equation and adding right atrial pressure estimated from central venous pressure
Myocardial isovolumic acceleration
Time frame: Measured after 20 minutes from the application of each of the four levels of PEEP
Ratio of lateral tricuspid annulus peak velocity during isovolumic contraction to acceleration time by pulsed-wave tissue Doppler imaging in the apical four-chamber view that achieves parallel alignment of Doppler beam with right ventricular free wall longitudinal excursion
Right ventricle stroke index
Time frame: Measured after 20 minutes from the application of each of the four levels of PEEP
Ratio of right ventricular stroke volume, calculated as product between velocity-time integral at the level of pulmonary valve and transverse area of right ventricular outflow tract in the aortic valve-level parasternal short axis view during systole, and body surface area
Right ventricle stroke work index
Time frame: Measured after 20 minutes from the application of each of the four levels of PEEP
Product between right ventricle stroke index and right ventricle systolic pressure
Right ventricular free wall longitudinal strain
Time frame: Measured after 20 minutes from the application of each of the four levels of PEEP
Peak value of longitudinal speckle-tracking-derived strain, averaged over the three segments of the right ventricular free wall, after manual tracing of right ventricular endocardial border from the lateral tricuspid annulus along the free wall to the apex and back to medial tricuspid annulus in right ventricle-focused apical four-chamber view
10 secondary outcomes
Ventilator settings
Time frame: Measured after 20 minutes from the application of each of the four levels of PEEP
Respiratory mechanics
Time frame: Measured after 20 minutes from the application of each of the four levels of PEEP
Arterial blood gas analysis
Time frame: Measured after 20 minutes from the application of each of the four levels of PEEP
Dead space
Time frame: Measured after 20 minutes from the application of each of the four levels of PEEP
Ventilatory ratio
Time frame: Measured after 20 minutes from the application of each of the four levels of PEEP
Shunt
Time frame: Measured after 20 minutes from the application of the intervention
Hemodynamics
Time frame: Measured after 20 minutes from the application of the intervention
Pleural and lung ultrasound
Time frame: Measured after 20 minutes from the application of the intervention
Renal ultrasound
Time frame: Measured after 20 minutes from the application of the intervention
Ultrasound image quality
Time frame: Measured after 20 minutes from the application of the intervention
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 7 May 2026.
- Background: PubMed 29466596Fan E, Brodie D, Slutsky AS. Acute Respiratory Distress Syndrome: Advances in Diagnosis and Treatment. JAMA. 2018 Feb 20;319(7):698-710. doi: 10.1001/jama.2017.21907.
- Background: PubMed 22797452ARDS Definition Task Force; Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669.
- Background: PubMed 26781952Gattinoni L, Marini JJ, Pesenti A, Quintel M, Mancebo J, Brochard L. The "baby lung" became an adult. Intensive Care Med. 2016 May;42(5):663-673. doi: 10.1007/s00134-015-4200-8. Epub 2016 Jan 18.
- Background: PubMed 26903337Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291.
- Background: PubMed 27040102Bein T, Grasso S, Moerer O, Quintel M, Guerin C, Deja M, Brondani A, Mehta S. The standard of care of patients with ARDS: ventilatory settings and rescue therapies for refractory hypoxemia. Intensive Care Med. 2016 May;42(5):699-711. doi: 10.1007/s00134-016-4325-4. Epub 2016 Apr 4.
- Background: PubMed 21470008Herridge MS, Tansey CM, Matte A, Tomlinson G, Diaz-Granados N, Cooper A, Guest CB, Mazer CD, Mehta S, Stewart TE, Kudlow P, Cook D, Slutsky AS, Cheung AM; Canadian Critical Care Trials Group. Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med. 2011 Apr 7;364(14):1293-304. doi: 10.1056/NEJMoa1011802.
- Background: PubMed 10793162Acute Respiratory Distress Syndrome Network; Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8. doi: 10.1056/NEJM200005043421801.
- Background: PubMed 23688302Guerin C, Reignier J, Richard JC, Beuret P, Gacouin A, Boulain T, Mercier E, Badet M, Mercat A, Baudin O, Clavel M, Chatellier D, Jaber S, Rosselli S, Mancebo J, Sirodot M, Hilbert G, Bengler C, Richecoeur J, Gainnier M, Bayle F, Bourdin G, Leray V, Girard R, Baboi L, Ayzac L; PROSEVA Study Group. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013 Jun 6;368(23):2159-68. doi: 10.1056/NEJMoa1214103. Epub 2013 May 20.
- Background: PubMed 20843245Papazian L, Forel JM, Gacouin A, Penot-Ragon C, Perrin G, Loundou A, Jaber S, Arnal JM, Perez D, Seghboyan JM, Constantin JM, Courant P, Lefrant JY, Guerin C, Prat G, Morange S, Roch A; ACURASYS Study Investigators. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010 Sep 16;363(12):1107-16. doi: 10.1056/NEJMoa1005372.
- Background: PubMed 16231069Tremblay LN, Slutsky AS. Ventilator-induced lung injury: from the bench to the bedside. Intensive Care Med. 2006 Jan;32(1):24-33. doi: 10.1007/s00134-005-2817-8. Epub 2005 Oct 18. No abstract available.
- Background: PubMed 22216838Kuipers MT, van der Poll T, Schultz MJ, Wieland CW. Bench-to-bedside review: Damage-associated molecular patterns in the onset of ventilator-induced lung injury. Crit Care. 2011;15(6):235. doi: 10.1186/cc10437. Epub 2011 Nov 30.
- Background: PubMed 24283226Slutsky AS, Ranieri VM. Ventilator-induced lung injury. N Engl J Med. 2013 Nov 28;369(22):2126-36. doi: 10.1056/NEJMra1208707. No abstract available.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Tommaso Pettenuzzo, MD principal investigator
Institute of Anesthesiology and Intensive Care, Padova University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Positive end-expiratory pressure titration in people with Acute Respiratory Distress Syndrome and Right Ventricular Dysfunction, run by University of Padova 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 3 inclusion and 7 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 7 May 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?
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?
Right ventricle diameter 1 (time frame: Measured after 20 minutes from the application of each of the four levels of PEEP). The study lists 12 primary outcomes in all. 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 NCT05583461, which also lists 43 linked publications.
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 7 May 2026.