Lung Transplant; ComplicationsINTEGRATIONNCT07017608
Inspiratory Work of Breathing Before and After Extubation
An observational study of Lung Transplant; Complications and Ventilator-Induced Lung Injury, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
Critically ill patients who (1) are not able to maintain their airway, (2) cannot breathe on their own, or (3) both, are ones who often require tracheal intubation and support from a breathing machine (mechanical ventilator). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Transplant; Complications, Ventilator-Induced Lung Injury, Ventilator Associated Pneumonia
- How many people
- 67 participants
- Where
- 1 siteCanada
- Study dates
- 1 Sep 2020to Dec 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: Eligible patients admitted to the medical surgical intensive care unit (MSICU) at Toronto General Hospital (TGH) requiring invasive mechanical ventilation, after obtaining consent. Inclusion will be stratified in a 1:1 ratio between lung transplant and non-transplant patients.
Who may be able to join
- Adult patients intubated and ventilated
Who cannot join
- Contraindication for esophageal catheter insertion: upper gastrointestinal surgery within prior 6 weeks, actively bleeding esophageal varices
- Bronchopleural fistula
- Contraindication for electrical impedance tomography: chest burns, skin lesions in the thorax, chest wall bandaging limiting electrode placement, unstable spinal lesions or fractures
- Pregnancy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Toronto General Hospital, University Health Network
Toronto, Ontario, M5G2C4
Ewan Goligher, MD, 416-340-4800 ext. 6810, ewan.goligher@uhn.ca
About this study
Critically ill patients who (1) are not able to maintain their airway, (2) cannot breathe on their own, or (3) both, are ones who often require tracheal intubation and support from a breathing machine (mechanical ventilator). When the patient is ready to be liberated from the mechanical ventilator because the initial insult for intubation has been resolved, the patient is screened using the readiness to wean test in preparation for extubation. As the patient passes this screening, a spontaneous breathing test (SBT) is initiated. Currently, there are many debates surrounding which SBT technique is most favorable. At Toronto General Hospital, the clinical team uses a zero-end expiratory pressure (ZEEP) trial. Once the patient successfully passes their SBT they are then extubated.
The patient will undergo a spontaneous breathing trial of continuous positive airway pressure (CPAP) of 5 cmH2O and ZEEP, in which time the investigators will be using a new technology called electrical impedance tomography (EIT), to study and compare the end expiratory lung volume (EELV); investigators will use an esophageal catheter to measure and monitor pressures in the lung, and also assess the patient's work of breathing. This will be repeated once the patient has been extubated safely.
Read the detailed description
Detailed Description:
Many patients in intensive critical care require mechanical ventilation. Once the underlying reasons for intubating critically ill patients have been addressed, healthcare providers aim to allow patients to return to breathing spontaneously and to safely remove the endotracheal tube (ETT) at the earliest appropriate time. Unnecessarily delaying the removal of the ETT (extubation) may cause diaphragm muscle weakening or introduce ventilator induced pneumonia (VAP), ventilator induced lung injury (VILI) and ventilator induced diaphragm dysfunction. Thus, it is important to determine when a patient is ready to be weaned from mechanical ventilation in a timely manner.
Spontaneous breathing trials (SBTs) can be used to aid in assessing a patient's readiness for extubation. There is currently no clear consensus on which technique is the most beneficial as there are uncertainties about how different SBT strategies impact both gas exchange and the work of breathing (WOB) before and after extubation. At Toronto General Hospital (TGH), patients are placed on a zero positive end expiratory pressure (ZEEP) SBT trial. It has been argued that the resistance from ETT increases WOB while a patient is on ZEEP, and this added effort may be eased through the use of low levels of pressure support or CPAP, which could potentially improve the success of extubation processes. Additionally, maintaining some amount of positive end expiratory pressure (PEEP) during SBT might improve oxygenation and WOB.
This study aims to understand how the zero positive end expiratory pressure (ZEEP) trial affects lung function and breathing effort in lung transplant patients who require mechanical ventilation in the ICU. The use of tools such as Esophageal and gastric balloon (NutriVent, Sidam, Mirandola, Italy), EIT (Drager PulmoVista 500), Pneumotachograph, FluxMed respiratory monitor, and Respiratory muscle ultrasound will be used to measure lung function, respiratory mechanics, muscle function, arterial blood gas, gastric pressure and esophageal pressure.
After enrolling 27 participants, this study has been amended to address an additional new objective - the validation of non-invasive occlusion maneuvers to estimate expiratory muscle pressure. Expiratory activity is a phenomenon that can provide important insights during mechanical ventilation and during an SBT trial. EELV might decrease due to expiratory muscle activity, possibly impairing gas exchange and increasing lung elastance due to collapse. Currently, the use of a gastric balloon is the gold standard method to assess expiratory effort and enable quantification of expiratory muscle pressure by expiratory variation of gastric pressure (∆Pga). However, the gastric balloon is an invasive tool that presents several downsides, as a high cost and the need for expertise in balloon calibration and waveform analysis. This highlights the need for non-invasive methods to detect and quantify expiratory muscle activity. The ability of occlusion maneuvers to detect presence of expiratory muscle effort measured with the gold standard (gastric pressure) will be assessed with receiver operating characteristic curves. A total of 40 patients will be enrolled to address this objective, in addition to the 27 patients already enrolled, for a total of 67 patients. Of the first 27 patients enrolled, only 15 underwent study procedures. Going forward, a patient will be considered enrolled if they undergo study procedures.
- Conditions
- Lung Transplant; Complications, Ventilator-Induced Lung Injury, Ventilator Associated Pneumonia
- Medical subject headings
- Ventilator-Induced Lung Injury, Pneumonia, Ventilator-Associated
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in end-expiratory lung volume (EELV) between the varying conditions (CPAP 5, ZEEP, and post-extubation).
End-expiratory lung volume is assessed using Electrical Impedance Tomography (EIT) and expressed in milliliters (mL) across all three conditions:
- CPAP 5 cm H₂O
- ZEEP (Zero End-Expiratory Pressure)
- Post-extubation
Measured: Up to 30 minutes after extubation
Discriminative ability of occlusion maneuvers to detect expiratory muscle effort
The ability of occlusion maneuvers to detect presence of expiratory muscle effort, measured with the gold standard (gastric pressure), will be assessed with receiver operating characteristic curves.
Measured: Up to 30 minutes after spontaneous breathing trial initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2025
- Study start1 Sep 2020
- Primary completionJun 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung Transplant; ComplicationsStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- 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
- Case only
- Time perspective
- Prospective
- Enrolment
- 67 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ewan Goligher, University Health Network, Toronto
- Investigators
- Ewan Goligher, MD, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07017608
- Sponsor's protocol ID
- 19-5879
- Acronym
- INTEGRATION
- Status last verified
- May 2025
- First submitted
- 23 May 2025
- Last updated
- 12 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inspiratory Work of Breathing Before and After Extubation
- ClinicalTrials.gov ID
- NCT07017608
- Acronym / sponsor ID
- INTEGRATION / 19-5879
- Conditions
- Lung Transplant; Complications, Ventilator-Induced Lung Injury, Ventilator Associated Pneumonia
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 67 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- 1 Sep 2020 (actual)
- Primary completion
- Jun 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 12 Jun 2025 (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.
Critically ill patients who (1) are not able to maintain their airway, (2) cannot breathe on their own, or (3) both, are ones who often require tracheal intubation and support from a breathing machine (mechanical ventilator). When the patient is ready to be liberated from the mechanical ventilator because the initial insult for intubation has been resolved, the patient is screened using the readiness to wean test in preparation for extubation. As the patient passes this screening, a spontaneous breathing test (SBT) is initiated. Currently, there are many debates surrounding which SBT technique is most favorable. At Toronto General Hospital, the clinical team uses a zero-end expiratory pressure (ZEEP) trial. Once the patient successfully passes their SBT they are then extubated.
The patient will undergo a spontaneous breathing trial of continuous positive airway pressure (CPAP) of 5 cmH2O and ZEEP, in which time the investigators will be using a new technology called electrical impedance tomography (EIT), to study and compare the end expiratory lung volume (EELV); investigators will use an esophageal catheter to measure and monitor pressures in the lung, and also assess the patient's work of breathing. This will be repeated once the patient has been extubated safely.
Detailed description
Detailed Description:
Many patients in intensive critical care require mechanical ventilation. Once the underlying reasons for intubating critically ill patients have been addressed, healthcare providers aim to allow patients to return to breathing spontaneously and to safely remove the endotracheal tube (ETT) at the earliest appropriate time. Unnecessarily delaying the removal of the ETT (extubation) may cause diaphragm muscle weakening or introduce ventilator induced pneumonia (VAP), ventilator induced lung injury (VILI) and ventilator induced diaphragm dysfunction. Thus, it is important to determine when a patient is ready to be weaned from mechanical ventilation in a timely manner.
Spontaneous breathing trials (SBTs) can be used to aid in assessing a patient's readiness for extubation. There is currently no clear consensus on which technique is the most beneficial as there are uncertainties about how different SBT strategies impact both gas exchange and the work of breathing (WOB) before and after extubation. At Toronto General Hospital (TGH), patients are placed on a zero positive end expiratory pressure (ZEEP) SBT trial. It has been argued that the resistance from ETT increases WOB while a patient is on ZEEP, and this added effort may be eased through the use of low levels of pressure support or CPAP, which could potentially improve the success of extubation processes. Additionally, maintaining some amount of positive end expiratory pressure (PEEP) during SBT might improve oxygenation and WOB.
This study aims to understand how the zero positive end expiratory pressure (ZEEP) trial affects lung function and breathing effort in lung transplant patients who require mechanical ventilation in the ICU. The use of tools such as Esophageal and gastric balloon (NutriVent, Sidam, Mirandola, Italy), EIT (Drager PulmoVista 500), Pneumotachograph, FluxMed respiratory monitor, and Respiratory muscle ultrasound will be used to measure lung function, respiratory mechanics, muscle function, arterial blood gas, gastric pressure and esophageal pressure.
After enrolling 27 participants, this study has been amended to address an additional new objective - the validation of non-invasive occlusion maneuvers to estimate expiratory muscle pressure. Expiratory activity is a phenomenon that can provide important insights during mechanical ventilation and during an SBT trial. EELV might decrease due to expiratory muscle activity, possibly impairing gas exchange and increasing lung elastance due to collapse. Currently, the use of a gastric balloon is the gold standard method to assess expiratory effort and enable quantification of expiratory muscle pressure by expiratory variation of gastric pressure (∆Pga). However, the gastric balloon is an invasive tool that presents several downsides, as a high cost and the need for expertise in balloon calibration and waveform analysis. This highlights the need for non-invasive methods to detect and quantify expiratory muscle activity. The ability of occlusion maneuvers to detect presence of expiratory muscle effort measured with the gold standard (gastric pressure) will be assessed with receiver operating characteristic curves. A total of 40 patients will be enrolled to address this objective, in addition to the 27 patients already enrolled, for a total of 67 patients. Of the first 27 patients enrolled, only 15 underwent study procedures. Going forward, a patient will be considered enrolled if they undergo study procedures.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Eligible patients admitted to the medical surgical intensive care unit (MSICU) at Toronto General Hospital (TGH) requiring invasive mechanical ventilation, after obtaining consent. Inclusion will be stratified in a 1:1 ratio between lung transplant and non-transplant patients.
Key inclusion criteria (1 listed)
- Adult patients intubated and ventilated
Key exclusion criteria (4 listed)
- Contraindication for esophageal catheter insertion: upper gastrointestinal surgery within prior 6 weeks, actively bleeding esophageal varices
- Bronchopleural fistula
- Contraindication for electrical impedance tomography: chest burns, skin lesions in the thorax, chest wall bandaging limiting electrode placement, unstable spinal lesions or fractures
- Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change in end-expiratory lung volume (EELV) between the varying conditions (CPAP 5, ZEEP, and post-extubation).
Time frame: Up to 30 minutes after extubation
End-expiratory lung volume is assessed using Electrical Impedance Tomography (EIT) and expressed in milliliters (mL) across all three conditions: 1. CPAP 5 cm H₂O 2. ZEEP (Zero End-Expiratory Pressure) 3. Post-extubation
Discriminative ability of occlusion maneuvers to detect expiratory muscle effort
Time frame: Up to 30 minutes after spontaneous breathing trial initiation
The ability of occlusion maneuvers to detect presence of expiratory muscle effort, measured with the gold standard (gastric pressure), will be assessed with receiver operating characteristic curves.
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 12 Jun 2025.
- 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.
Ewan Goligher, MD principal investigator
University Health Network, Toronto
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 Lung Transplant; Complications and Ventilator-Induced Lung Injury, run by University Health Network, Toronto at 1 site in Canada.
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 4 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 12 Jun 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 Canada. 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 Glauco Plens, MD (416-340-4800 ext. 7613, Glauco.Plens@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in end-expiratory lung volume (EELV) between the varying conditions (CPAP 5, ZEEP, and post-extubation). (time frame: Up to 30 minutes after extubation). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Jun 2025.