An interventional study of Positive end-expiratory pressure titration in Acute Respiratory Distress Syndrome and Right Ventricular Dysfunction, sponsored by University of Padova. Completed at 1 site in Italy. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-05-07.
Sponsored by University of Padova · Not applicable, Interventional, and Diagnostic
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.
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 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.
1,387 studies on the registry are indexed under Respiratory Distress Syndrome; 283 are open to participants now.
This study's enrollment of 10 is below the median of 60 across 822 interventional studies indexed under Respiratory Distress Syndrome.
Browse Respiratory Distress Syndrome studies →University of Padova is the lead sponsor of 215 studies on the registry; 42 are open to participants now.
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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
Procedure: Positive end-expiratory pressure titration
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
Procedure: Positive end-expiratory pressure titration
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
Procedure: Positive end-expiratory pressure titration
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
Procedure: Positive end-expiratory pressure titration
Positive end-expiratory pressure level
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
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Measured after 20 minutes from the application of each of the four levels of PEEP
Ventilator settings
Tidal volume, respiratory rate, fraction of inspired oxygen, inspiratory to expiratory time
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: Measured after 20 minutes from the application of the intervention
Pleural and lung ultrasound
Lung ultrasound score, lung reaeration score
Time frame: Measured after 20 minutes from the application of the intervention
Renal ultrasound
Renal resistive index, renal venous stasis index
Time frame: 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
Time frame: Measured after 20 minutes from the application of the intervention
Plan to share: No
Ran from Oct 2022 to primary completion in Dec 2025, 38 months.
Of 263 non-industry interventional studies with no phase under Respiratory Distress Syndrome, half reached primary completion within 24 months of starting (the median), counting those still running; a quarter within 12 and three quarters within 42. This study's 38 months is above that.
Counting every sponsor, half of 270 studies reached it within 24 months; a quarter within 12 and three quarters within 42.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in May 2026. You cannot join it, but the record below documents what was studied.
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