Right Heart FailureNCT05922631
Effect of APRV vs. LTV on Right Heart Function in ARDS Patients: a Single-center Randomized Controlled Study
A study testing Airway pressure release ventilation and low tidal volume in people with Right Heart Failure and Mechanical Ventilation, run by XiaoJing Zou,MD at 1 site in China.
Trial summary
Acute Respiratory Distress Syndrome (ARDS) is often complicated by Right Ventricular Dysfunction (RVD), and the incidence can be as high as 64%. The mechanism includes pulmonary vascular dysfunction and right heart systolic dysfunction. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Right Heart Failure, Mechanical Ventilation, Acute Respiratory Distress Syndrome
- What is being tested?
- Airway pressure release ventilation and low tidal volume
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteChina
- Study dates
- 3 Jul 2023to 1 Feb 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Patients who meet the 2012 Berlin ARDS diagnostic criteria and perform invasive mechanical ventilation 2, PEEP≥5cmH2O, oxygenation index ≤200mmHg 3. Tracheal intubation and mechanical ventilation were performed for less than 48h at the time of inclusion 4. Age ≥18 years and ≤80 years
Who cannot join
- 1.abdominal pressure≥20mmHg 2.BMI≥35kg/m2; 3. pregnant and lactating women 4.expected duration of invasive mechanical ventilation < 72 hours 5. neuromuscular diseases known to require prolonged mechanical ventilation 6.severe chronic obstructive pulmonary disease, severe asthma, Interstitial lung disease 7.intracranial hypertension, 8.pulmonary bullae or pneumothorax, subcutaneous emphysema, or mediastinal emphysema, 9.extracorporeal membrane oxygenation or prone position ventilation on admission to the ICU 10. uncorrected shock of various types and refractory shock 11.pulmonary embolism 12.severe cardiac dysfunction (New York Heart Association class III or IV). Acute coronary syndrome or sustained ventricular tachyarrhythmia), right heart enlargement due to chronic cardiopulmonary diseases, cardiogenic shock or after major cardiac surgery 13.poor cardiac sound window, unable to obtain cardiac ultrasound images 14.no informed consent was signed
Trial locations and contacts
1 site in 1 country.
China1 site
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, 430000
About this study
Official title: Effect of Airway Pressure Release Ventilation vs. Low Tidal Volume Ventilation on Right Heart Function in Acute Respiratory Distress Syndrome Patients: a Single-center Randomized Controlled Study
Acute Respiratory Distress Syndrome (ARDS) is often complicated by Right Ventricular Dysfunction (RVD), and the incidence can be as high as 64%. The mechanism includes pulmonary vascular dysfunction and right heart systolic dysfunction. Pulmonary vascular dysfunction includes acute vascular inflammation, pulmonary vascular edema, thrombosis and pulmonary vascular remodeling. Alveolar collapse and over distension can also lead to increased pulmonary vascular resistance, Preventing the development of acute cor pulmonale in patients with acute respiratory distress. ARDS patients with RVD have a worse prognosis and a significantly increased risk of death, which is an independent risk factor for death in ARDS patients. Therefore, implementing a right heart-protective mechanical ventilation strategy may reduce the incidence of RVD.
APRV is an inverse mechanical ventilation mode with transient pressure release under continuous positive airway pressure, which can effectively improve oxygenation and reduce ventilator-associated lung injury. However, its effect on right ventricular function is still controversial. Low tidal volume (LTV) is a mechanical ventilation strategy widely used in ARDS patients. Meta-analysis results showed that compared with LTV, APRV improved oxygenation more significantly, reduced the time of mechanical ventilation, and even had a tendency to improve the mortality of ARDS patients However, randomized controlled studies have shown that compared with LTV, APRV improves oxygenation more significantly and also increases the mean airway pressure. Therefore, some scholars speculate that APRV may increase the intrathoracic pressure, pulmonary circulatory resistance, and the risk of right heart dysfunction but this speculation is not supported by clinical research evidence. In addition, APRV may improve right ventricular function by correcting hypoxia and hypercapnia, promoting lung recruitment and reducing pulmonary circulation resistance. Therefore, it is very important to clarify this effect for whether APRV can be safely used and popularized in clinic.we aim to conduct a single-center randomized controlled study to further compare the effects of APRV and LTV on right ventricular function in patients with ARDS, pulmonary circulatory resistance (PVR) right ventricular-pulmonary artery coupling (RV-PA coupling), and pulmonary vascular resistance (PVR).
Read the detailed description
Acute Respiratory DistressSyndrome (ARDS) is often complicated by Right Ventricular Dysfunction (RVD), and the incidence can be as high as 64%. The mechanism includes pulmonary vascular dysfunction and right heart systolic dysfunction. Pulmonary vascular dysfunction includes acute vascular inflammation, pulmonary vascular edema, thrombosis and pulmonary vascular remodeling. Alveolar collapse and alveolar overdistension can also lead to increased pulmonary vascular resistance, Preventing the development of acute cor pulmonale in patients with acute respiratory distress. ARDS patients with RVD have a worse prognosis and a significantly increased risk of death, which is an independent risk factor for death in ARDS patients [2-4]. Therefore, implementing a right heart-protective mechanical ventilation strategy may reduce the incidence of RVD.
Mechanical ventilation is the main treatment for moderate to severe ARDS. Mechanical ventilation promotes lung recruitment and reduces mechanical compression of pulmonary vessels between alveoli and alveolar walls. In addition, mechanical ventilation corrected hypoxemia and hypercapnia, thereby reducing reactive pulmonary vasoconstriction. All of the above can reduce pulmonary circulation resistance and right ventricular afterload, thereby improving right ventricular function in patients with ARDS. However, if hyperventilation occurs, it will increase the mechanical compression of pulmonary vessels on the alveolar wall, increase the intrathoracic pressure, and increase the afterload of the right heart, which will adversely affect the function of the right heart. There are a variety of ventilation strategies for patients with ARDS in clinical practice, but which mechanical ventilation has the protective function of right heart or has little effect on right heart function, so far there is a lack of relevant research reports.
Airway pressure release ventilation (APRV) is an inverse mechanical ventilation mode with transient pressure release under continuous positive airway pressure, which can effectively improve oxygenation and reduce ventilator-associated lung injury. However, its effect on right ventricular function is still controversial, so its clinical application is not popular, and it is only used as one of the salvage treatments for ARDS patients. Low tidal volume (LTV) is a mechanical ventilation strategy widely used in ARDS patients, but it does not further reduce mortality in patients with moderate to severe ARDS. Meta-analysis results showed that compared with LTV, APRV improved oxygenation more significantly, reduced the time of mechanical ventilation, and even had a tendency to improve the mortality of ARDS patients [7]. However, randomized controlled studies have shown that compared with LTV, APRV improves oxygenation more significantly and also increases the mean airway pressure [8]. Therefore, some scholars speculate that APRV may increase the intrathoracic pressure, pulmonary circulatory resistance, and the risk of right heart dysfunction , but this speculation is not supported by clinical research evidence. In addition, the results of animal experiments suggest that APRV improves oxygenation, promotes lung recruitment, and improves the heterogeneity of lung lesions in ARDS, without causing lung hyperventilation, suggesting that APRV may not increase pulmonary circulatory resistance. In addition, APRV may improve right ventricular function by correcting hypoxia and hypercapnia, promoting lung recruitment and reducing pulmonary circulation resistance. Therefore, the impact of APRV on right ventricular function is still unclear, and it is very important to clarify this effect for whether APRV can be safely used and popularized in clinic. Therefore, our research group conducted a prospective observational study, "The effect of APRV on right ventricular function evaluated by Transthoracic Echocardiography, [2022] Lun Lun Zi (0075)". The study results suggested that APRV improved lung perfusion in ARDS patients while effectively improving oxygenation and promoting lung recruitment. The incidence of RVD was not increased, and there was no hemodynamic deterioration in ARDS patients. APRV is safe and effective for patients with ARDS. However, the results of a single-arm prospective observational study with a small sample size cannot provide strong evidence for clinical practice. In the previous studies, all the right ventricular function was assessed by transthoracic echocardiography. Due to the limitation of the sound window of transthoracic echocardiography, the right ventricular function of some ARDS patients could not be evaluated. Therefore, this study intends to use transesophageal echocardiography or transthoracic echocardiography to fully evaluate the right ventricular function of all enrolled patients as much as possible, and to conduct a single-center randomized controlled study to further compare the effects of APRV and LTV on right ventricular function in patients with ARDS, pulmonary circulatory resistance (PVR), right ventricular-pulmonary artery coupling (RV-PA coupling), and pulmonary vascular resistance (PVR).Whether there are different effects on hemodynamics and mortality. It is hoped that the results of this study will provide more evidence support for the clinical application of APRV and benefit more ARDS patients.
- Being tested
- Airway pressure release ventilation, low tidal volume
- Medical subject headings
- Heart Failure, Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Airway pressure release ventilationProcedure or surgery
ventilator parameters were set according to the study protocol, P high: Tidal volume (VT) was set at 6ml/kg of ideal body weight, and plateau pressure (Pplat) was measured. Initial Phigh was set at Pplat, usually 20-32 cmH2O. The APRV end-expiratory flow rate was set at 75% of the peak expiratory flow rate.
low tidal volumeProcedure or surgery
The ARDSnet method was used for LTV mechanical ventilation, and the tidal volume was set according to 4-8ml/kg, so that the Pplat was <30cmH2O
| Study group | Role | What they receive |
|---|---|---|
| APRV group | Experimental | In APRV group, ventilator parameters were set according to the study protocol, P high: Tidal volume (VT) was set at 6ml/kg of ideal body weight, and plateau pressure (Pplat) was measured. Initial Phigh was set at Pplat, usually 20-32 cmH2O. The APRV end-expiratory flow rate was set at 75% of the peak expiratory flow rate. Receives: Procedure: Airway pressure release ventilation |
| LTV group | Placebo comparator | The ARDSnet method was used for LTV group mechanical ventilation, and the tidal volume was set according to 4-8ml/kg, so that the Pplat was <30cmH2O Receives: Procedure: low tidal volume |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of right heart dysfunction in ARDS patients with APRV or LTV mechanical ventilation for 24h
Incidence of right heart dysfunction in ARDS patients with APRV or LTV mechanical ventilation for 24h.Abnormal findings on any of the following ultrasound measures can be considered as right ventricular dysfunction, including: tricuspid annular plane systolic excursion (TAPSE) <17 mm, tricuspid annular plane systolic velocity (S') <9.5 cm/s, right ventricular fractional area change (FAC) <35%, ratio of right ventricular end-diastolic area to left ventricular end-diastolic area (RVEDA/LVEDA) >0.6, or right ventricular to left ventricular end-diastolic diameter ratio (RV/LV ratio) >1.
Measured: at the time of 24 hours after inclusion
Secondary outcomes (31)
Incidence of right heart dysfunction in ARDS patients with APRV or LTV mechanical ventilation for 48h
Incidence of right heart dysfunction in ARDS patients with APRV or LTV mechanical ventilation for 24h.Abnormal findings on any of the following ultrasound measures can be considered as right ventricular dysfunction, including: right ventricular end-diastolic diameter/left ventricular end-diastolic diameter(RVEDD/LVEDD)>1.0, right ventricular fractional area change(FAC)<35%,tricuspid annular plane systolic excursion(TAPSE)<17mm,Systolic S'velocity of tricuspid annulus <9.5 cm/s by TDI
Measured: at the time of 48 hours after inclusion
Incidence of right heart dysfunction in ARDS patients with APRV or LTV mechanical ventilation for 72h
Incidence of right heart dysfunction in ARDS patients with APRV or LTV mechanical ventilation for 24h.Abnormal findings on any of the following ultrasound measures can be considered as right ventricular dysfunction, including: right ventricular end-diastolic diameter/left ventricular end-diastolic diameter(RVEDD/LVEDD)>1.0, right ventricular fractional area change(FAC)<35%,tricuspid annular plane systolic excursion(TAPSE)<17mm,Systolic S'velocity of tricuspid annulus <9.5 cm/s by TDI
Measured: at the time of 72 hours after inclusion
Values of tricuspid annular plane systolic excursion at 24th hour
Tricuspid annular plane systolic excursion(TAPSE) was measured by echocardiography in the apical four-chamber view, using M mode measurements, with the sampling line aligned to the tricuspid annulus.
Measured: at the time of 24 hours after inclusion
Values of tricuspid annular plane systolic excursion at 48th hour
Tricuspid annular plane systolic excursion(TAPSE) was measured by echocardiography in the apical four-chamber view, using M mode measurements, with the sampling line aligned to the tricuspid annulus.
Measured: at the time of 48 hours after inclusion
Values of tricuspid annular plane systolic excursion at 72th hour
Tricuspid annular plane systolic excursion(TAPSE) was measured by echocardiography in the apical four-chamber view, using M mode measurements, with the sampling line aligned to the tricuspid annulus.
Measured: at the time of 72 hours after inclusion
Values of right ventricular end-diastolic diameter/left ventricular end-diastolic diameter(RVEDD/LVEDD) at 24th hour
The maximum transverse diameter of the right/left ventricular inflow tract near the basal 1/3 was measured in the apical four-chamber view
Measured: at the time of 24 hours after inclusion
Values of right ventricular end-diastolic diameter/left ventricular end-diastolic diameter(RVEDD/LVEDD) at 48th hour
The maximum transverse diameter of the right/left ventricular inflow tract near the basal 1/3 was measured in the apical four-chamber view
Measured: at the time of 48 hours after inclusion
Values of right ventricular end-diastolic diameter/left ventricular end-diastolic diameter(RVEDD/LVEDD) at 72th hour
The maximum transverse diameter of the right/left ventricular inflow tract near the basal 1/3 was measured in the apical four-chamber view
Measured: at the time of 72 hours after inclusion
Values of right ventricular fractional area change(RVFAC) at 24th hour
RVFAC = (end-diastolic area - end-systolic area)/end-diastolic area ×100%.The right ventricle is shown in the apical four-chamber cardiac view.
Measured: at the time of 24 hours after inclusion
Values of right ventricular fractional area change(RVFAC) at 48th hour
RVFAC = (end-diastolic area - end-systolic area)/end-diastolic area ×100%.The right ventricle is shown in the apical four-chamber cardiac view.
Measured: at the time of 48 hours after inclusion
Values of right ventricular fractional area change(RVFAC) at 72th hour
RVFAC = (end-diastolic area - end-systolic area)/end-diastolic area ×100%.The right ventricle is shown in the apical four-chamber cardiac view.
Measured: at the time of 72 hours after inclusion
Values of Systolic S'velocity of tricuspid annulus by at 24th, 48th and 72th hour
Tissue Doppler sampling volume is placed in the middle of the right ventricular tricuspid annulus or basal segment of the right ventricular free wall to measure systolic velocity S'.
Measured: at the time of 24 hours (h), 48h and 72h after inclusion
Values of hemodynamic measures at 24th, 48th and 72th hour
hemodynamic measures including: heart rate, mean arterial pressure,central venous pressure,Dose of vasoactive agents accumulated over 24 hours,cumulative fluid balance over 24 hours.
Measured: at the time of 24 hours (h), 48h and 72h after inclusion
Values of respiratory mechanics parameters at 24th, 48th and 72th hour
Respiratory mechanics parameters including Peak pressure, Plateau pressure,Driving pressure,Respiratory system compliance and Airway resistance are measured by using routine procedures
Measured: at the time of 24 hours (h), 48h and 72h after inclusion
28-day mortality
28-day mortality after study entry
Measured: Day 28 after study entry
in hospital mortality
in hospital mortality after study entry
Measured: Maximum 90-day in-hospital mortality
28 days of ventilator free days
28 days of ventilator free days after study entry
Measured: Day 28 after study entry
Values of arterial partial pressure of oxygen/fraction of inspired oxygen at 24th, 48th and 72th hour
arterial partial pressure of oxygen/fraction of inspired oxygen are measured at 24th, 48th and 72th hour after inclusion
Measured: at the time of 24 hours (h), 48h and 72h after inclusion
Values of arterial partial pressure of carbon dioxide at 24th, 48th and 72th hour
arterial partial pressure of carbon dioxide are measured at 24th, 48th and 72th hour after inclusion
Measured: at the time of 24 hours (h), 48h and 72h after inclusion
ventilation ratio at 24th, 48th and 72th hour
VR=[minute ventilation ×PaCO2]/[predicted body weight ×100×37.5]
Measured: at the time of 24 hours (h), 48h and 72h after inclusion
Incidence prone position ventilation during hospitalization
Incidence of prone position ventilation during hospitalization after study entry
Measured: Day 28 after study entry
ventilator settings at 24th, 48th and 72th hour
ventilator settings including minute ventilation, Fraction of inspired oxygen, tidal volume, positive end-expiratory pressure, respiratory rate, mean airway pressure
Measured: at the time of 24 hours (h), 48h and 72h after inclusion
Velocity-time integral of left ventricular outflow tract at 24th, 48th and 72th hour
Velocity-time integral(Vti) of left ventricular outflow tract are measured at the apical five-chamber heart view. The sampling volume was placed in the left ventricular outflow tract, below the aortic valve, in pulsed Doppler mode with a window width of 2-4mm. The velocity time integral (VTI) image of aortic blood flow can be obtained by placing the sampling volume below the aortic valve orifice , adjusting the probe so that the direction of blood flow is as parallel as possible to the sampling line, and selecting the pulsed Doppler mode (PW)
Measured: at the time of 24 hours (h), 48h and 72h after inclusion
Stroke volume at 24th, 48th and 72th hour
Stroke volume(SV)=15.VTI×π(D/2)*(D/2), D=Left ventricular outflow tract diameter(LVOT diameter)
Measured: at the time of 24 hours (h), 48h and 72h after inclusion
cardiac output at 24th, 48th and 72th hour
cardiac output(CO)=SV*HR
Measured: at the time of 24 hours (h), 48h and 72h after inclusion
Velocity-time integral of right ventricular outflow tract at 24th, 48th and 72th hour
Velocity-time integral(Vti) of right ventricular outflow tract are measured at the view of the right ventricular outflow tract. The sampling volume was placed in the right ventricular outflow tract, below the aortic valve, in pulsed Doppler mode with a window width of 2-4mm. The velocity time integral (VTI) image of aortic blood flow can be obtained by placing the sampling volume below the aortic valve orifice , adjusting the probe so that the direction of blood flow is as parallel as possible to the sampling line, and selecting the pulsed Doppler mode (PW)
Measured: at the time of 24 hours (h), 48h and 72h after inclusion
Tricuspid annular diameter
Tricuspid annular diameters are measured at the apical four-chamber heart view
Measured: at the time of 24 hours (h), 48h and 72h after inclusion
The velocity of tricuspid regurgitation
The velocity of tricuspid regurgitation are measured at the apical four-chamber heart view.The CW Doppler sampling line was placed at the tricuspid valve orifice.
Measured: at the time of 24 hours (h), 48h and 72h after inclusion
Length of hospital stay
hospital stay after hospital entry
Measured: Maximum 90-day hospital stay
Length of ICU stay
hospital stay after ICU entry
Measured: Maximum 90-day ICU stay
Incidence of tracheotomy
Incidence of tracheotomy during hospitalization after study entry
Measured: Day 28 after study entry
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2023
- Study start3 Jul 2023
- Primary completion1 Feb 2025
- Study completion1 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Right Heart FailureStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients with ARDS who met the inclusion criteria were randomized to APRV or LTV mechanical ventilation. Ventilator parameters were set according to the study protocol, P high: Tidal volume (VT) was set at 6ml/kg of ideal body weight, and plateau pressure (Pplat) was measured. Initial Phigh was set at Pplat, usually 20-32 cmH2O. The APRV end-expiratory flow rate was set at 75% of the peak expiratory flow rate. For LTV mechanical ventilation, ARDSnet method was used to set the tidal volume according to 4-8ml/kg, so that Pplat\<30cmH2O
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- XiaoJing Zou,MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, XiaoJing Zou,MD, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Investigators
- Xiaojing zou, MD, Study director, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05922631
- Sponsor's protocol ID
- ALRVD2022
- Status last verified
- May 2025
- First submitted
- 19 Jun 2023
- Last updated
- 18 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Zhang H, Huang W, Zhang Q, Chen X, Wang X, Liu D; Critical Care Ultrasound Study Group. Prevalence and prognostic value of various types of right ventricular dysfunction in mechanically ventilated septic patients. Ann Intensive Care. 2021 Jul 13;11(1):108. doi: 10.1186/s13613-021-00902-9.
PubMed 34255224Boissier F, Katsahian S, Razazi K, Thille AW, Roche-Campo F, Leon R, Vivier E, Brochard L, Vieillard-Baron A, Brun-Buisson C, Mekontso Dessap A. Prevalence and prognosis of cor pulmonale during protective ventilation for acute respiratory distress syndrome. Intensive Care Med. 2013 Oct;39(10):1725-33. doi: 10.1007/s00134-013-2941-9. Epub 2013 May 15.
PubMed 23673401Dong D, Zong Y, Li Z, Wang Y, Jing C. Mortality of right ventricular dysfunction in patients with acute respiratory distress syndrome subjected to lung protective ventilation: A systematic review and meta-analysis. Heart Lung. 2021 Sep-Oct;50(5):730-735. doi: 10.1016/j.hrtlng.2021.04.011. Epub 2021 Jun 9.
PubMed 34118786Mekontso Dessap A, Boissier F, Charron C, Begot E, Repesse X, Legras A, Brun-Buisson C, Vignon P, Vieillard-Baron A. Acute cor pulmonale during protective ventilation for acute respiratory distress syndrome: prevalence, predictors, and clinical impact. Intensive Care Med. 2016 May;42(5):862-870. doi: 10.1007/s00134-015-4141-2. Epub 2015 Dec 9.
PubMed 26650055Sipmann FS, Santos A, Tusman G. Heart-lung interactions in acute respiratory distress syndrome: pathophysiology, detection and management strategies. Ann Transl Med. 2018 Jan;6(2):27. doi: 10.21037/atm.2017.12.07.
PubMed 29430444Cheng J, Ma A, Dong M, Zhou Y, Wang B, Xue Y, Wang P, Yang J, Kang Y. Does airway pressure release ventilation offer new hope for treating acute respiratory distress syndrome? J Intensive Med. 2022 Mar 28;2(4):241-248. doi: 10.1016/j.jointm.2022.02.003. eCollection 2022 Oct.
PubMed 36785647Sun X, Liu Y, Li N, You D, Zhao Y. The safety and efficacy of airway pressure release ventilation in acute respiratory distress syndrome patients: A PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore). 2020 Jan;99(1):e18586. doi: 10.1097/MD.0000000000018586.
PubMed 31895807Zhou Y, Jin X, Lv Y, Wang P, Yang Y, Liang G, Wang B, Kang Y. Early application of airway pressure release ventilation may reduce the duration of mechanical ventilation in acute respiratory distress syndrome. Intensive Care Med. 2017 Nov;43(11):1648-1659. doi: 10.1007/s00134-017-4912-z. Epub 2017 Sep 22.
PubMed 28936695Andrews P, Shiber J, Madden M, Nieman GF, Camporota L, Habashi NM. Myths and Misconceptions of Airway Pressure Release Ventilation: Getting Past the Noise and on to the Signal. Front Physiol. 2022 Jul 25;13:928562. doi: 10.3389/fphys.2022.928562. eCollection 2022.
PubMed 35957991Robinson B, Ebeid M. A simple echocardiographic method to estimate pulmonary vascular resistance. Am J Cardiol. 2014 Jan 15;113(2):412. doi: 10.1016/j.amjcard.2013.11.001. Epub 2013 Nov 7. No abstract available.
PubMed 24387904
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Airway Pressure Release Ventilation vs. Low Tidal Volume Ventilation on Right Heart Function in Acute Respiratory Distress Syndrome Patients: a Single-center Randomized Controlled Study
- ClinicalTrials.gov ID
- NCT05922631
- Acronym / sponsor ID
- ALRVD2022
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- XiaoJing Zou,MDUniversity, hospital or other
- Study start
- 3 Jul 2023 (actual)
- Primary completion
- 1 Feb 2025 (actual)
- Study completion
- 1 Feb 2025 (actual)
- First posted
- 28 Jun 2023 (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.
Acute Respiratory Distress Syndrome (ARDS) is often complicated by Right Ventricular Dysfunction (RVD), and the incidence can be as high as 64%. The mechanism includes pulmonary vascular dysfunction and right heart systolic dysfunction. Pulmonary vascular dysfunction includes acute vascular inflammation, pulmonary vascular edema, thrombosis and pulmonary vascular remodeling. Alveolar collapse and over distension can also lead to increased pulmonary vascular resistance, Preventing the development of acute cor pulmonale in patients with acute respiratory distress. ARDS patients with RVD have a worse prognosis and a significantly increased risk of death, which is an independent risk factor for death in ARDS patients. Therefore, implementing a right heart-protective mechanical ventilation strategy may reduce the incidence of RVD.
APRV is an inverse mechanical ventilation mode with transient pressure release under continuous positive airway pressure, which can effectively improve oxygenation and reduce ventilator-associated lung injury. However, its effect on right ventricular function is still controversial. Low tidal volume (LTV) is a mechanical ventilation strategy widely used in ARDS patients. Meta-analysis results showed that compared with LTV, APRV improved oxygenation more significantly, reduced the time of mechanical ventilation, and even had a tendency to improve the mortality of ARDS patients However, randomized controlled studies have shown that compared with LTV, APRV improves oxygenation more significantly and also increases the mean airway pressure. Therefore, some scholars speculate that APRV may increase the intrathoracic pressure, pulmonary circulatory resistance, and the risk of right heart dysfunction but this speculation is not supported by clinical research evidence. In addition, APRV may improve right ventricular function by correcting hypoxia and hypercapnia, promoting lung recruitment and reducing pulmonary circulation resistance. Therefore, it is very important to clarify this effect for whether APRV can be safely used and popularized in clinic.we aim to conduct a single-center randomized controlled study to further compare the effects of APRV and LTV on right ventricular function in patients with ARDS, pulmonary circulatory resistance (PVR) right ventricular-pulmonary artery coupling (RV-PA coupling), and pulmonary vascular resistance (PVR).
Detailed description
Acute Respiratory DistressSyndrome (ARDS) is often complicated by Right Ventricular Dysfunction (RVD), and the incidence can be as high as 64%. The mechanism includes pulmonary vascular dysfunction and right heart systolic dysfunction. Pulmonary vascular dysfunction includes acute vascular inflammation, pulmonary vascular edema, thrombosis and pulmonary vascular remodeling. Alveolar collapse and alveolar overdistension can also lead to increased pulmonary vascular resistance, Preventing the development of acute cor pulmonale in patients with acute respiratory distress. ARDS patients with RVD have a worse prognosis and a significantly increased risk of death, which is an independent risk factor for death in ARDS patients [2-4]. Therefore, implementing a right heart-protective mechanical ventilation strategy may reduce the incidence of RVD.
Mechanical ventilation is the main treatment for moderate to severe ARDS. Mechanical ventilation promotes lung recruitment and reduces mechanical compression of pulmonary vessels between alveoli and alveolar walls. In addition, mechanical ventilation corrected hypoxemia and hypercapnia, thereby reducing reactive pulmonary vasoconstriction. All of the above can reduce pulmonary circulation resistance and right ventricular afterload, thereby improving right ventricular function in patients with ARDS. However, if hyperventilation occurs, it will increase the mechanical compression of pulmonary vessels on the alveolar wall, increase the intrathoracic pressure, and increase the afterload of the right heart, which will adversely affect the function of the right heart. There are a variety of ventilation strategies for patients with ARDS in clinical practice, but which mechanical ventilation has the protective function of right heart or has little effect on right heart function, so far there is a lack of relevant research reports.
Airway pressure release ventilation (APRV) is an inverse mechanical ventilation mode with transient pressure release under continuous positive airway pressure, which can effectively improve oxygenation and reduce ventilator-associated lung injury. However, its effect on right ventricular function is still controversial, so its clinical application is not popular, and it is only used as one of the salvage treatments for ARDS patients. Low tidal volume (LTV) is a mechanical ventilation strategy widely used in ARDS patients, but it does not further reduce mortality in patients with moderate to severe ARDS. Meta-analysis results showed that compared with LTV, APRV improved oxygenation more significantly, reduced the time of mechanical ventilation, and even had a tendency to improve the mortality of ARDS patients [7]. However, randomized controlled studies have shown that compared with LTV, APRV improves oxygenation more significantly and also increases the mean airway pressure [8]. Therefore, some scholars speculate that APRV may increase the intrathoracic pressure, pulmonary circulatory resistance, and the risk of right heart dysfunction , but this speculation is not supported by clinical research evidence. In addition, the results of animal experiments suggest that APRV improves oxygenation, promotes lung recruitment, and improves the heterogeneity of lung lesions in ARDS, without causing lung hyperventilation, suggesting that APRV may not increase pulmonary circulatory resistance. In addition, APRV may improve right ventricular function by correcting hypoxia and hypercapnia, promoting lung recruitment and reducing pulmonary circulation resistance. Therefore, the impact of APRV on right ventricular function is still unclear, and it is very important to clarify this effect for whether APRV can be safely used and popularized in clinic. Therefore, our research group conducted a prospective observational study, "The effect of APRV on right ventricular function evaluated by Transthoracic Echocardiography, [2022] Lun Lun Zi (0075)". The study results suggested that APRV improved lung perfusion in ARDS patients while effectively improving oxygenation and promoting lung recruitment. The incidence of RVD was not increased, and there was no hemodynamic deterioration in ARDS patients. APRV is safe and effective for patients with ARDS. However, the results of a single-arm prospective observational study with a small sample size cannot provide strong evidence for clinical practice. In the previous studies, all the right ventricular function was assessed by transthoracic echocardiography. Due to the limitation of the sound window of transthoracic echocardiography, the right ventricular function of some ARDS patients could not be evaluated. Therefore, this study intends to use transesophageal echocardiography or transthoracic echocardiography to fully evaluate the right ventricular function of all enrolled patients as much as possible, and to conduct a single-center randomized controlled study to further compare the effects of APRV and LTV on right ventricular function in patients with ARDS, pulmonary circulatory resistance (PVR), right ventricular-pulmonary artery coupling (RV-PA coupling), and pulmonary vascular resistance (PVR).Whether there are different effects on hemodynamics and mortality. It is hoped that the results of this study will provide more evidence support for the clinical application of APRV and benefit more ARDS patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Patients with ARDS who met the inclusion criteria were randomized to APRV or LTV mechanical ventilation. Ventilator parameters were set according to the study protocol, P high: Tidal volume (VT) was set at 6ml/kg of ideal body weight, and plateau pressure (Pplat) was measured. Initial Phigh was set at Pplat, usually 20-32 cmH2O. The APRV end-expiratory flow rate was set at 75% of the peak expiratory flow rate. For LTV mechanical ventilation, ARDSnet method was used to set the tidal volume according to 4-8ml/kg, so that Pplat<30cmH2O
| Arm | Type | Receives |
|---|---|---|
| APRV group | Experimental | Procedure: Airway pressure release ventilationIn APRV group, ventilator parameters were set according to the study protocol, P high: Tidal volume (VT) was set at 6ml/kg of ideal body weight, and plateau pressure (Pplat) was measured. Initial Phigh was set at Pplat, usually 20-32 cmH2O. The APRV end-expiratory flow rate was set at 75% of the peak expiratory flow rate. |
| LTV group | Placebo comparator | Procedure: low tidal volumeThe ARDSnet method was used for LTV group mechanical ventilation, and the tidal volume was set according to 4-8ml/kg, so that the Pplat was <30cmH2O |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 1. Patients who meet the 2012 Berlin ARDS diagnostic criteria and perform invasive mechanical ventilation 2, PEEP≥5cmH2O, oxygenation index ≤200mmHg 3. Tracheal intubation and mechanical ventilation were performed for less than 48h at the time of inclusion 4. Age ≥18 years and ≤80 years
Key exclusion criteria (1 listed)
- 1.abdominal pressure≥20mmHg 2.BMI≥35kg/m2; 3. pregnant and lactating women 4.expected duration of invasive mechanical ventilation < 72 hours 5. neuromuscular diseases known to require prolonged mechanical ventilation 6.severe chronic obstructive pulmonary disease, severe asthma, Interstitial lung disease 7.intracranial hypertension, 8.pulmonary bullae or pneumothorax, subcutaneous emphysema, or mediastinal emphysema, 9.extracorporeal membrane oxygenation or prone position ventilation on admission to the ICU 10. uncorrected shock of various types and refractory shock 11.pulmonary embolism 12.severe cardiac dysfunction (New York Heart Association class III or IV). Acute coronary syndrome or sustained ventricular tachyarrhythmia), right heart enlargement due to chronic cardiopulmonary diseases, cardiogenic shock or after major cardiac surgery 13.poor cardiac sound window, unable to obtain cardiac ultrasound images 14.no informed consent was signed
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 |
|---|---|---|
| Airway pressure release ventilationventilator parameters were set according to the study protocol, P high: Tidal volume (VT) was set at 6ml/kg of ideal body weight, and plateau pressure (Pplat) was measured. Initial Phigh was set at Pplat, usually 20-32 cmH2O. The APRV end-expiratory flow rate was set at 75% of the peak expiratory flow rate. | Procedure or surgery | APRV group |
| low tidal volumeThe ARDSnet method was used for LTV mechanical ventilation, and the tidal volume was set according to 4-8ml/kg, so that the Pplat was <30cmH2O | Procedure or surgery | LTV group |
Primary outcome
Incidence of right heart dysfunction in ARDS patients with APRV or LTV mechanical ventilation for 24h
Time frame: at the time of 24 hours after inclusion
Incidence of right heart dysfunction in ARDS patients with APRV or LTV mechanical ventilation for 24h.Abnormal findings on any of the following ultrasound measures can be considered as right ventricular dysfunction, including: tricuspid annular plane systolic excursion (TAPSE) <17 mm, tricuspid annular plane systolic velocity (S') <9.5 cm/s, right ventricular fractional area change (FAC) <35%, ratio of right ventricular end-diastolic area to left ventricular end-diastolic area (RVEDA/LVEDA) >0.6, or right ventricular to left ventricular end-diastolic diameter ratio (RV/LV ratio) >1.
31 secondary outcomes
Incidence of right heart dysfunction in ARDS patients with APRV or LTV mechanical ventilation for 48h
Time frame: at the time of 48 hours after inclusion
Incidence of right heart dysfunction in ARDS patients with APRV or LTV mechanical ventilation for 72h
Time frame: at the time of 72 hours after inclusion
Values of tricuspid annular plane systolic excursion at 24th hour
Time frame: at the time of 24 hours after inclusion
Values of tricuspid annular plane systolic excursion at 48th hour
Time frame: at the time of 48 hours after inclusion
Values of tricuspid annular plane systolic excursion at 72th hour
Time frame: at the time of 72 hours after inclusion
Values of right ventricular end-diastolic diameter/left ventricular end-diastolic diameter(RVEDD/LVEDD) at 24th hour
Time frame: at the time of 24 hours after inclusion
Values of right ventricular end-diastolic diameter/left ventricular end-diastolic diameter(RVEDD/LVEDD) at 48th hour
Time frame: at the time of 48 hours after inclusion
Values of right ventricular end-diastolic diameter/left ventricular end-diastolic diameter(RVEDD/LVEDD) at 72th hour
Time frame: at the time of 72 hours after inclusion
Values of right ventricular fractional area change(RVFAC) at 24th hour
Time frame: at the time of 24 hours after inclusion
Values of right ventricular fractional area change(RVFAC) at 48th hour
Time frame: at the time of 48 hours after inclusion
Values of right ventricular fractional area change(RVFAC) at 72th hour
Time frame: at the time of 72 hours after inclusion
Values of Systolic S'velocity of tricuspid annulus by at 24th, 48th and 72th hour
Time frame: at the time of 24 hours (h), 48h and 72h after inclusion
Values of hemodynamic measures at 24th, 48th and 72th hour
Time frame: at the time of 24 hours (h), 48h and 72h after inclusion
Values of respiratory mechanics parameters at 24th, 48th and 72th hour
Time frame: at the time of 24 hours (h), 48h and 72h after inclusion
28-day mortality
Time frame: Day 28 after study entry
in hospital mortality
Time frame: Maximum 90-day in-hospital mortality
28 days of ventilator free days
Time frame: Day 28 after study entry
Values of arterial partial pressure of oxygen/fraction of inspired oxygen at 24th, 48th and 72th hour
Time frame: at the time of 24 hours (h), 48h and 72h after inclusion
Values of arterial partial pressure of carbon dioxide at 24th, 48th and 72th hour
Time frame: at the time of 24 hours (h), 48h and 72h after inclusion
ventilation ratio at 24th, 48th and 72th hour
Time frame: at the time of 24 hours (h), 48h and 72h after inclusion
Incidence prone position ventilation during hospitalization
Time frame: Day 28 after study entry
ventilator settings at 24th, 48th and 72th hour
Time frame: at the time of 24 hours (h), 48h and 72h after inclusion
Velocity-time integral of left ventricular outflow tract at 24th, 48th and 72th hour
Time frame: at the time of 24 hours (h), 48h and 72h after inclusion
Stroke volume at 24th, 48th and 72th hour
Time frame: at the time of 24 hours (h), 48h and 72h after inclusion
cardiac output at 24th, 48th and 72th hour
Time frame: at the time of 24 hours (h), 48h and 72h after inclusion
Velocity-time integral of right ventricular outflow tract at 24th, 48th and 72th hour
Time frame: at the time of 24 hours (h), 48h and 72h after inclusion
Tricuspid annular diameter
Time frame: at the time of 24 hours (h), 48h and 72h after inclusion
The velocity of tricuspid regurgitation
Time frame: at the time of 24 hours (h), 48h and 72h after inclusion
Length of hospital stay
Time frame: Maximum 90-day hospital stay
Length of ICU stay
Time frame: Maximum 90-day ICU stay
Incidence of tracheotomy
Time frame: Day 28 after study entry
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 18 Sep 2025.
- Background: PubMed 34255224Zhang H, Huang W, Zhang Q, Chen X, Wang X, Liu D; Critical Care Ultrasound Study Group. Prevalence and prognostic value of various types of right ventricular dysfunction in mechanically ventilated septic patients. Ann Intensive Care. 2021 Jul 13;11(1):108. doi: 10.1186/s13613-021-00902-9.
- Background: PubMed 23673401Boissier F, Katsahian S, Razazi K, Thille AW, Roche-Campo F, Leon R, Vivier E, Brochard L, Vieillard-Baron A, Brun-Buisson C, Mekontso Dessap A. Prevalence and prognosis of cor pulmonale during protective ventilation for acute respiratory distress syndrome. Intensive Care Med. 2013 Oct;39(10):1725-33. doi: 10.1007/s00134-013-2941-9. Epub 2013 May 15.
- Background: PubMed 34118786Dong D, Zong Y, Li Z, Wang Y, Jing C. Mortality of right ventricular dysfunction in patients with acute respiratory distress syndrome subjected to lung protective ventilation: A systematic review and meta-analysis. Heart Lung. 2021 Sep-Oct;50(5):730-735. doi: 10.1016/j.hrtlng.2021.04.011. Epub 2021 Jun 9.
- Background: PubMed 26650055Mekontso Dessap A, Boissier F, Charron C, Begot E, Repesse X, Legras A, Brun-Buisson C, Vignon P, Vieillard-Baron A. Acute cor pulmonale during protective ventilation for acute respiratory distress syndrome: prevalence, predictors, and clinical impact. Intensive Care Med. 2016 May;42(5):862-870. doi: 10.1007/s00134-015-4141-2. Epub 2015 Dec 9.
- Background: PubMed 29430444Sipmann FS, Santos A, Tusman G. Heart-lung interactions in acute respiratory distress syndrome: pathophysiology, detection and management strategies. Ann Transl Med. 2018 Jan;6(2):27. doi: 10.21037/atm.2017.12.07.
- Background: PubMed 36785647Cheng J, Ma A, Dong M, Zhou Y, Wang B, Xue Y, Wang P, Yang J, Kang Y. Does airway pressure release ventilation offer new hope for treating acute respiratory distress syndrome? J Intensive Med. 2022 Mar 28;2(4):241-248. doi: 10.1016/j.jointm.2022.02.003. eCollection 2022 Oct.
- Background: PubMed 31895807Sun X, Liu Y, Li N, You D, Zhao Y. The safety and efficacy of airway pressure release ventilation in acute respiratory distress syndrome patients: A PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore). 2020 Jan;99(1):e18586. doi: 10.1097/MD.0000000000018586.
- Background: PubMed 28936695Zhou Y, Jin X, Lv Y, Wang P, Yang Y, Liang G, Wang B, Kang Y. Early application of airway pressure release ventilation may reduce the duration of mechanical ventilation in acute respiratory distress syndrome. Intensive Care Med. 2017 Nov;43(11):1648-1659. doi: 10.1007/s00134-017-4912-z. Epub 2017 Sep 22.
- Background: PubMed 35957991Andrews P, Shiber J, Madden M, Nieman GF, Camporota L, Habashi NM. Myths and Misconceptions of Airway Pressure Release Ventilation: Getting Past the Noise and on to the Signal. Front Physiol. 2022 Jul 25;13:928562. doi: 10.3389/fphys.2022.928562. eCollection 2022.
- Background: PubMed 24387904Robinson B, Ebeid M. A simple echocardiographic method to estimate pulmonary vascular resistance. Am J Cardiol. 2014 Jan 15;113(2):412. doi: 10.1016/j.amjcard.2013.11.001. Epub 2013 Nov 7. No abstract available.
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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.
Xiaojing zou, MD study director
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Airway pressure release ventilation and low tidal volume in people with Right Heart Failure and Mechanical Ventilation, run by XiaoJing Zou,MD at 1 site in China.
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 1 inclusion and 1 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 18 Sep 2025. 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 China. 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. Some participants in this study may receive a placebo. 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?
Incidence of right heart dysfunction in ARDS patients with APRV or LTV mechanical ventilation for 24h (time frame: at the time of 24 hours after inclusion). 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 NCT05922631, which also lists 10 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 18 Sep 2025.