Acute Respiratory Distress SyndromeNCT04524091
Prediction of Inspiratory Effort Response to High PEEP in Patients Recovering From ARDS
An observational study of Acute Respiratory Distress Syndrome, run by Sanatorio Anchorena San Martin at 1 site in Argentina.
Trial summary
Spontaneous breathing during the transition from controlled to assisted ventilation in ARDS may be harmful, as high respiratory drive can generate large transpulmonary pressure swings and worsen lung injury. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Respiratory Distress Syndrome
- What is being tested?
- Positive end expiratory pressure
- How many people
- 30 participants
- Where
- 1 siteArgentina
- Study dates
- 1 Aug 2020to 1 Aug 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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
Study population: Patients with acute respiratory distress syndrome ventilated using an endotracheal tube admitted to Anchorena San Martin intensive care unit who are ventilated in pressure support ventilation.
Who may be able to join
- Need of invasive mechanical ventilation
- Patients who had fulfill ARDS criteria based on Berlin definition during any time of invasive mechanical ventilation.
- Patient ventilated in pressure support ventilation.
- Time of invasive ventilation expected to be longer than 24 hs after the day of enrollment.
Who cannot join
- Neuromuscular diseases (e.g., amyotrophic lateral sclerosis, Duchenne Erb)
- previous diagnosis of chronic obstructed pulmonary disease
- not resolved pneumothorax
- bronchopleural fistula
- suspicion of central respiratory drive alteration (e.g., benzodiazepines intoxication).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Argentina1 site, 1 recruiting
- Recruiting
Sanatorio Anchorena de San Martin
San Martín, Buenos Aires, B1650CQU
Joaquin Perez, PT, licjoaquinperez@hotmail.com
About this study
Spontaneous breathing during the transition from controlled to assisted ventilation in ARDS may be harmful, as high respiratory drive can generate large transpulmonary pressure swings and worsen lung injury. Higher PEEP may mitigate this by reducing inspiratory effort and lung stress, but patient response is variable and difficult to predict. While improved lung compliance appears to mediate the protective effects of PEEP, its bedside assessment is complex. Preclinical data suggest that changes in compliance are inversely reflected by changes in respiratory rate, but this relationship and its clinical utility in ARDS patients remain unclear.
Read the detailed description
Spontaneous Breathing (SB) can be potentially harmful in patient with Acute Respiratory Distress Syndrome (ARDS) during the transition phase of passive ventilation to partial ventilatory support. A high respiratory drive and consequently, a strong inspiratory effort, may produce large transpulmonary pressure (TP) swings mainly in dependent lung regions closer to the diaphragm and cause alveolar rupture and inflammatory mediators release.
The application of high Positive End Expiratory Pressure (PEEP) during SB has shown to ameliorate the progression of lung injury by decreasing the TP and esophageal pressure (EP) swings and the stress / strain applied to the lung. However, it is uncertain which patient will respond adequately to the application of high PEEP and consequently will reduce the inspiratory effort.
Recent evidence suggests that high PEEP may confer protective effects when lung compliance improves. However, assessing lung compliance at the bedside is challenging, as it requires esophageal pressure monitoring. Simpler tools to identify lung compliance response to PEEP are neccesary.
Preclinical data suggest that the changes in compliance are followed by opposite changes in respiratory rate (RR) - i.e., if compliance improves, RR decreases and vicerversa. However, if this behaviour is also observed in ARDS patients ventilated at different PEEP levels is unkown. Additionally, whether changes in RR can be useful to identify changes in lung compliance when increasing PEEP has never been tested.
- Conditions
- Acute Respiratory Distress Syndrome
- Being tested
- Positive end expiratory pressure
- Medical subject headings
- Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Positive end expiratory pressureOther
Initially, the patients will be ventilated using pressure support ventilation with an inspiratory pressure adjusted to achieve 6 - 8 ml/kg of PBW with a minimal esophageal pressure swing of 5 cmH2O and a PEEP of 5 cmH2O. After 5 minutes, we will collect basic and advanced respiratory monitoring, including esophageal pressure and transpulmonary pressure swings. The same procedure will be carried out with 10 and 15 cmH2O of PEEP. Inspiratory pressure will be kept constant throughout the protocol.
What is being measured
The primary outcome is the main question the study is designed to answer.
Lung compliance response
changes in lung compliance from one PEEP level to the subsequent higher level, expressed in percentage of change
Measured: 10 minutes
Secondary outcomes (3)
Esophageal pressure swing
Esophageal pressure swing will be calculated as the difference between end expiration and end inspiration esophageal pressure during the las 30-60 seconds of each PEEP condition evaluated
Measured: 10 minutes
Dynamic transpulmonary pressure swing
Dynamic transpulmonary pressure swing will be calculated as the difference between end expiration and end inspiration dynamic transpulmonary pressure during the las 30-60 seconds of each PEEP condition evaluated
Measured: 10 minutes
Respiratory rate response
changes in respiratory rate from one PEEP level to the subsequent higher level, expressed in percentage of change
Measured: 10 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2020
- Study start1 Aug 2020
- Primary completion1 Apr 2026
- Study completion1 Aug 2026 (estimated)
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 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sanatorio Anchorena San Martin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Matias Accoce, Sanatorio Anchorena San Martin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04524091
- Sponsor's protocol ID
- 20.2020
- Status last verified
- Apr 2026
- First submitted
- 19 Aug 2020
- Last updated
- 16 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Esteban A, Frutos-Vivar F, Muriel A, Ferguson ND, Penuelas O, Abraira V, Raymondos K, Rios F, Nin N, Apezteguia C, Violi DA, Thille AW, Brochard L, Gonzalez M, Villagomez AJ, Hurtado J, Davies AR, Du B, Maggiore SM, Pelosi P, Soto L, Tomicic V, D'Empaire G, Matamis D, Abroug F, Moreno RP, Soares MA, Arabi Y, Sandi F, Jibaja M, Amin P, Koh Y, Kuiper MA, Bulow HH, Zeggwagh AA, Anzueto A. Evolution of mortality over time in patients receiving mechanical ventilation. Am J Respir Crit Care Med. 2013 Jul 15;188(2):220-30. doi: 10.1164/rccm.201212-2169OC.
PubMed 23631814DAS-Taskforce 2015; Baron R, Binder A, Biniek R, Braune S, Buerkle H, Dall P, Demirakca S, Eckardt R, Eggers V, Eichler I, Fietze I, Freys S, Frund A, Garten L, Gohrbandt B, Harth I, Hartl W, Heppner HJ, Horter J, Huth R, Janssens U, Jungk C, Kaeuper KM, Kessler P, Kleinschmidt S, Kochanek M, Kumpf M, Meiser A, Mueller A, Orth M, Putensen C, Roth B, Schaefer M, Schaefers R, Schellongowski P, Schindler M, Schmitt R, Scholz J, Schroeder S, Schwarzmann G, Spies C, Stingele R, Tonner P, Trieschmann U, Tryba M, Wappler F, Waydhas C, Weiss B, Weisshaar G. Evidence and consensus based guideline for the management of delirium, analgesia, and sedation in intensive care medicine. Revision 2015 (DAS-Guideline 2015) - short version. Ger Med Sci. 2015 Nov 12;13:Doc19. doi: 10.3205/000223. eCollection 2015.
PubMed 26609286Schepens T, Dres M, Heunks L, Goligher EC. Diaphragm-protective mechanical ventilation. Curr Opin Crit Care. 2019 Feb;25(1):77-85. doi: 10.1097/MCC.0000000000000578.
PubMed 30531536Mauri T, Cambiaghi B, Spinelli E, Langer T, Grasselli G. Spontaneous breathing: a double-edged sword to handle with care. Ann Transl Med. 2017 Jul;5(14):292. doi: 10.21037/atm.2017.06.55.
PubMed 28828367Goligher EC, Fan E, Herridge MS, Murray A, Vorona S, Brace D, Rittayamai N, Lanys A, Tomlinson G, Singh JM, Bolz SS, Rubenfeld GD, Kavanagh BP, Brochard LJ, Ferguson ND. Evolution of Diaphragm Thickness during Mechanical Ventilation. Impact of Inspiratory Effort. Am J Respir Crit Care Med. 2015 Nov 1;192(9):1080-8. doi: 10.1164/rccm.201503-0620OC.
PubMed 26167730Telias I, Brochard L, Goligher EC. Is my patient's respiratory drive (too) high? Intensive Care Med. 2018 Nov;44(11):1936-1939. doi: 10.1007/s00134-018-5091-2. Epub 2018 Mar 1. No abstract available.
PubMed 29497778Brochard L, Slutsky A, Pesenti A. Mechanical Ventilation to Minimize Progression of Lung Injury in Acute Respiratory Failure. Am J Respir Crit Care Med. 2017 Feb 15;195(4):438-442. doi: 10.1164/rccm.201605-1081CP.
PubMed 27626833Morais CCA, Koyama Y, Yoshida T, Plens GM, Gomes S, Lima CAS, Ramos OPS, Pereira SM, Kawaguchi N, Yamamoto H, Uchiyama A, Borges JB, Vidal Melo MF, Tucci MR, Amato MBP, Kavanagh BP, Costa ELV, Fujino Y. High Positive End-Expiratory Pressure Renders Spontaneous Effort Noninjurious. Am J Respir Crit Care Med. 2018 May 15;197(10):1285-1296. doi: 10.1164/rccm.201706-1244OC.
PubMed 29323536Yoshida T, Uchiyama A, Matsuura N, Mashimo T, Fujino Y. Spontaneous breathing during lung-protective ventilation in an experimental acute lung injury model: high transpulmonary pressure associated with strong spontaneous breathing effort may worsen lung injury. Crit Care Med. 2012 May;40(5):1578-85. doi: 10.1097/CCM.0b013e3182451c40.
PubMed 22430241Mauri T, Bellani G, Confalonieri A, Tagliabue P, Turella M, Coppadoro A, Citerio G, Patroniti N, Pesenti A. Topographic distribution of tidal ventilation in acute respiratory distress syndrome: effects of positive end-expiratory pressure and pressure support. Crit Care Med. 2013 Jul;41(7):1664-73. doi: 10.1097/CCM.0b013e318287f6e7.
PubMed 23507723
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prediction of Inspiratory Effort Response to High PEEP in Patients Recovering From ARDS
- ClinicalTrials.gov ID
- NCT04524091
- Acronym / sponsor ID
- 20.2020
- Conditions
- Acute Respiratory Distress Syndrome
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Sanatorio Anchorena San MartinUniversity, hospital or other
- Study start
- 1 Aug 2020 (actual)
- Primary completion
- 1 Apr 2026 (actual)
- Study completion
- 1 Aug 2026 (estimated)
- First posted
- 24 Aug 2020 (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.
Spontaneous breathing during the transition from controlled to assisted ventilation in ARDS may be harmful, as high respiratory drive can generate large transpulmonary pressure swings and worsen lung injury. Higher PEEP may mitigate this by reducing inspiratory effort and lung stress, but patient response is variable and difficult to predict. While improved lung compliance appears to mediate the protective effects of PEEP, its bedside assessment is complex. Preclinical data suggest that changes in compliance are inversely reflected by changes in respiratory rate, but this relationship and its clinical utility in ARDS patients remain unclear.
Detailed description
Spontaneous Breathing (SB) can be potentially harmful in patient with Acute Respiratory Distress Syndrome (ARDS) during the transition phase of passive ventilation to partial ventilatory support. A high respiratory drive and consequently, a strong inspiratory effort, may produce large transpulmonary pressure (TP) swings mainly in dependent lung regions closer to the diaphragm and cause alveolar rupture and inflammatory mediators release.
The application of high Positive End Expiratory Pressure (PEEP) during SB has shown to ameliorate the progression of lung injury by decreasing the TP and esophageal pressure (EP) swings and the stress / strain applied to the lung. However, it is uncertain which patient will respond adequately to the application of high PEEP and consequently will reduce the inspiratory effort.
Recent evidence suggests that high PEEP may confer protective effects when lung compliance improves. However, assessing lung compliance at the bedside is challenging, as it requires esophageal pressure monitoring. Simpler tools to identify lung compliance response to PEEP are neccesary.
Preclinical data suggest that the changes in compliance are followed by opposite changes in respiratory rate (RR) - i.e., if compliance improves, RR decreases and vicerversa. However, if this behaviour is also observed in ARDS patients ventilated at different PEEP levels is unkown. Additionally, whether changes in RR can be useful to identify changes in lung compliance when increasing PEEP has never been tested.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with acute respiratory distress syndrome ventilated using an endotracheal tube admitted to Anchorena San Martin intensive care unit who are ventilated in pressure support ventilation.
Key inclusion criteria (4 listed)
- Need of invasive mechanical ventilation
- Patients who had fulfill ARDS criteria based on Berlin definition during any time of invasive mechanical ventilation.
- Patient ventilated in pressure support ventilation.
- Time of invasive ventilation expected to be longer than 24 hs after the day of enrollment.
Key exclusion criteria (5 listed)
- Neuromuscular diseases (e.g., amyotrophic lateral sclerosis, Duchenne Erb)
- previous diagnosis of chronic obstructed pulmonary disease
- not resolved pneumothorax
- bronchopleural fistula
- suspicion of central respiratory drive alteration (e.g., benzodiazepines intoxication).
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 pressureInitially, the patients will be ventilated using pressure support ventilation with an inspiratory pressure adjusted to achieve 6 - 8 ml/kg of PBW with a minimal esophageal pressure swing of 5 cmH2O and a PEEP of 5 cmH2O. After 5 minutes, we will collect basic and advanced respiratory monitoring, including esophageal pressure and transpulmonary pressure swings. The same procedure will be carried out with 10 and 15 cmH2O of PEEP. Inspiratory pressure will be kept constant throughout the protocol. | Other | – |
Primary outcome
Lung compliance response
Time frame: 10 minutes
changes in lung compliance from one PEEP level to the subsequent higher level, expressed in percentage of change
3 secondary outcomes
Esophageal pressure swing
Time frame: 10 minutes
Dynamic transpulmonary pressure swing
Time frame: 10 minutes
Respiratory rate response
Time frame: 10 minutes
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2026.
- Background: PubMed 23631814Esteban A, Frutos-Vivar F, Muriel A, Ferguson ND, Penuelas O, Abraira V, Raymondos K, Rios F, Nin N, Apezteguia C, Violi DA, Thille AW, Brochard L, Gonzalez M, Villagomez AJ, Hurtado J, Davies AR, Du B, Maggiore SM, Pelosi P, Soto L, Tomicic V, D'Empaire G, Matamis D, Abroug F, Moreno RP, Soares MA, Arabi Y, Sandi F, Jibaja M, Amin P, Koh Y, Kuiper MA, Bulow HH, Zeggwagh AA, Anzueto A. Evolution of mortality over time in patients receiving mechanical ventilation. Am J Respir Crit Care Med. 2013 Jul 15;188(2):220-30. doi: 10.1164/rccm.201212-2169OC.
- Background: PubMed 26609286DAS-Taskforce 2015; Baron R, Binder A, Biniek R, Braune S, Buerkle H, Dall P, Demirakca S, Eckardt R, Eggers V, Eichler I, Fietze I, Freys S, Frund A, Garten L, Gohrbandt B, Harth I, Hartl W, Heppner HJ, Horter J, Huth R, Janssens U, Jungk C, Kaeuper KM, Kessler P, Kleinschmidt S, Kochanek M, Kumpf M, Meiser A, Mueller A, Orth M, Putensen C, Roth B, Schaefer M, Schaefers R, Schellongowski P, Schindler M, Schmitt R, Scholz J, Schroeder S, Schwarzmann G, Spies C, Stingele R, Tonner P, Trieschmann U, Tryba M, Wappler F, Waydhas C, Weiss B, Weisshaar G. Evidence and consensus based guideline for the management of delirium, analgesia, and sedation in intensive care medicine. Revision 2015 (DAS-Guideline 2015) - short version. Ger Med Sci. 2015 Nov 12;13:Doc19. doi: 10.3205/000223. eCollection 2015.
- Background: PubMed 30531536Schepens T, Dres M, Heunks L, Goligher EC. Diaphragm-protective mechanical ventilation. Curr Opin Crit Care. 2019 Feb;25(1):77-85. doi: 10.1097/MCC.0000000000000578.
- Background: PubMed 28828367Mauri T, Cambiaghi B, Spinelli E, Langer T, Grasselli G. Spontaneous breathing: a double-edged sword to handle with care. Ann Transl Med. 2017 Jul;5(14):292. doi: 10.21037/atm.2017.06.55.
- Background: PubMed 26167730Goligher EC, Fan E, Herridge MS, Murray A, Vorona S, Brace D, Rittayamai N, Lanys A, Tomlinson G, Singh JM, Bolz SS, Rubenfeld GD, Kavanagh BP, Brochard LJ, Ferguson ND. Evolution of Diaphragm Thickness during Mechanical Ventilation. Impact of Inspiratory Effort. Am J Respir Crit Care Med. 2015 Nov 1;192(9):1080-8. doi: 10.1164/rccm.201503-0620OC.
- Background: PubMed 29497778Telias I, Brochard L, Goligher EC. Is my patient's respiratory drive (too) high? Intensive Care Med. 2018 Nov;44(11):1936-1939. doi: 10.1007/s00134-018-5091-2. Epub 2018 Mar 1. No abstract available.
- Background: PubMed 27626833Brochard L, Slutsky A, Pesenti A. Mechanical Ventilation to Minimize Progression of Lung Injury in Acute Respiratory Failure. Am J Respir Crit Care Med. 2017 Feb 15;195(4):438-442. doi: 10.1164/rccm.201605-1081CP.
- Background: PubMed 29323536Morais CCA, Koyama Y, Yoshida T, Plens GM, Gomes S, Lima CAS, Ramos OPS, Pereira SM, Kawaguchi N, Yamamoto H, Uchiyama A, Borges JB, Vidal Melo MF, Tucci MR, Amato MBP, Kavanagh BP, Costa ELV, Fujino Y. High Positive End-Expiratory Pressure Renders Spontaneous Effort Noninjurious. Am J Respir Crit Care Med. 2018 May 15;197(10):1285-1296. doi: 10.1164/rccm.201706-1244OC.
- Background: PubMed 22430241Yoshida T, Uchiyama A, Matsuura N, Mashimo T, Fujino Y. Spontaneous breathing during lung-protective ventilation in an experimental acute lung injury model: high transpulmonary pressure associated with strong spontaneous breathing effort may worsen lung injury. Crit Care Med. 2012 May;40(5):1578-85. doi: 10.1097/CCM.0b013e3182451c40.
- Background: PubMed 23507723Mauri T, Bellani G, Confalonieri A, Tagliabue P, Turella M, Coppadoro A, Citerio G, Patroniti N, Pesenti A. Topographic distribution of tidal ventilation in acute respiratory distress syndrome: effects of positive end-expiratory pressure and pressure support. Crit Care Med. 2013 Jul;41(7):1664-73. doi: 10.1097/CCM.0b013e318287f6e7.
- Individual participant dataSharing planned: Undecided
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Respiratory Distress Syndrome, run by Sanatorio Anchorena San Martin at 1 site in Argentina.
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 4 inclusion and 5 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: looking for participants now, as of the sponsor's last update on 16 Apr 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 Argentina. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Joaquin Pérez, PT (+542245505907, licjoaquinperez@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Lung compliance response (time frame: 10 minutes). 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 NCT04524091, 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 16 Apr 2026.