Diaphragm InjuryPhase 1LANDMARKNCT03612583
Lung and Diaphragm-Protective Ventilation by Means of Assessing Respiratory Work
A Phase 1 study testing Lung- and Diaphragm-Protective Ventilation in people with Diaphragm Injury and Lung Injury, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
This study is designed to test a proposed strategy for lung- and diaphragm-protective ventilation (LDPV) in patients with acute hypoxemic respiratory failure. Ventilation and sedation will be titrated to evaluate whether it is feasible and safe within this patient population. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diaphragm Injury, Lung Injury, Respiratory Insufficiency
- What is being tested?
- Lung- and Diaphragm-Protective Ventilation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteCanada
- Study dates
- 1 Feb 2019to 30 Nov 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosed with acute hypoxemic respiratory failure
- PaO2:FiO2 ratio less than or equal to 300 mm Hg at time of screening
- Oral endotracheal intubation and mechanical ventilation
- Bilateral airspace opacities on chest radiograph or chest CT scan
Who cannot join
- Liberation from mechanical ventilation is anticipated within 24 hours
- Intubated for traumatic brain injury or stroke
- Contraindication to esophageal catheterization
- Intracranial hypertension
Trial locations and contacts
1 site in 1 country.
About this study
This study is designed to test a proposed strategy for lung- and diaphragm-protective ventilation (LDPV) in patients with acute hypoxemic respiratory failure. Ventilation and sedation will be titrated to evaluate whether it is feasible and safe within this patient population.
Read the detailed description
Lung injury and diaphragm injury incurred by mechanical ventilation have very serious adverse effects on patients with acute respiratory failure. Lung injury results from excessive mechanical stress and strain applied to the lung by the ventilator and/or respiratory muscles, while diaphragm injury results from either insufficient or excessive inspiratory effort.
The objective of this study is to investigate a new LDPV strategy designed to prevent both disuse-mediated and load-induced diaphragm injury, while also preventing excess global and regional mechanical stress and strain in the injured lung. To achieve these goals, the following specific targets to be met are: (1) respiratory muscle effort similar to that of healthy subjects breathing at rest, (2) lung stress within safe limits, and (3) clinically acceptable gas exchange.
Targets are assessed through measurements of global lung stress, tidal recruitment, inspiratory effort, diaphragm contractile effort and adequacy of respiratory muscle and systemic tissue perfusion. Measurements commence at enrollment and continue for 24 hours consecutively.
- Conditions
- Diaphragm Injury, Lung Injury, Respiratory Insufficiency, Mechanical Ventilation Complication
- Being tested
- Lung- and Diaphragm-Protective Ventilation
- Keywords
- Diaphragm Dysfunction, Acute Respiratory Failure, Sedation, Mechanical Ventilation, Lung Stress
- Medical subject headings
- Lung Injury, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lung- and Diaphragm-Protective VentilationProcedure or surgery
Also called LDPV
Ventilation and sedation will be progressively modified according to the LDPV algorithm to achieve targets. Patients will be crossed-over to the opposite PEEP strategy. LDPV titration will then be repeated to achieve LDPV targets. After establishing a combination of ventilation and sedation settings at which LDPV targets are achieved, the targets will be maintained over a 24-hour period.
| Study group | Role | What they receive |
|---|---|---|
| Lower PEEP | Experimental | Lung- and Diaphragm-Protective Ventilation - PEEP will be set at 8 cm H2O Receives: Procedure: Lung- and Diaphragm-Protective Ventilation |
| Higher PEEP | Experimental | Lung- and Diaphragm-Protective Ventilation - PEEP will be titrated to achieve end-expiratory PL = 2-3 cm H20 and at least 5 cm H2O greater than the level applied in the lower PEEP arm Receives: Procedure: Lung- and Diaphragm-Protective Ventilation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of patients achieving and maintaining LDPV targets
Measured: Assessed after achievement of LDPV targets for 24 hours
Secondary outcomes (6)
Inspiratory effort at lower and higher PEEP levels
Measured: Assessed 10 minutes after PEEP and sedation are adjusted
Expiratory diaphragmatic effort at lower and higher PEEP levels
Measured: Assessed 10 minutes after PEEP and sedation are adjusted
Lung stress and strain at low and high sweep gas flow rates
Measured: Assessed 10 minutes after PEEP and sedation are adjusted
Inspiratory effort at low and high sweep gas flow rates
Measured: Assessed 10 minutes after PEEP and sedation are adjusted
Sedative infusion rate at low and high sweep gas flow rates
Measured: Assessed 10 minutes after PEEP and sedation are adjusted
Accuracy of artificial intelligence model in predicting patient outcomes
We will compare the model's prediction of patient's esophageal pressure, pH and transpulmonary pressure to the actual observed values
Measured: Assessed after completing the 24-hour maintenance period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2018
- Study start1 Feb 2019
- Primary completion30 Nov 2022
- Study completion30 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diaphragm InjuryStudies 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ewan Goligher, MD, PhD, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03612583
- Sponsor's protocol ID
- 18-5644
- Acronym
- LANDMARK
- Status last verified
- Dec 2024
- First submitted
- 5 Jul 2018
- Last updated
- 10 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Dianti J, Fard S, Wong J, Chan TCY, Del Sorbo L, Fan E, Amato MBP, Granton J, Burry L, Reid WD, Zhang B, Ratano D, Keshavjee S, Slutsky AS, Brochard LJ, Ferguson ND, Goligher EC. Strategies for lung- and diaphragm-protective ventilation in acute hypoxemic respiratory failure: a physiological trial. Crit Care. 2022 Aug 29;26(1):259. doi: 10.1186/s13054-022-04123-9.
PubMed 36038890
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lung and Diaphragm-Protective Ventilation by Means of Assessing Respiratory Work
- ClinicalTrials.gov ID
- NCT03612583
- Acronym / sponsor ID
- LANDMARK / 18-5644
- Conditions
- Diaphragm Injury, Lung Injury, Respiratory Insufficiency, Mechanical Ventilation Complication
- Keywords
- Diaphragm Dysfunction, Acute Respiratory Failure, Sedation, Mechanical Ventilation, Lung Stress
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- 1 Feb 2019 (actual)
- Primary completion
- 30 Nov 2022 (actual)
- Study completion
- 30 Nov 2022 (actual)
- First posted
- 2 Aug 2018 (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.
This study is designed to test a proposed strategy for lung- and diaphragm-protective ventilation (LDPV) in patients with acute hypoxemic respiratory failure. Ventilation and sedation will be titrated to evaluate whether it is feasible and safe within this patient population.
Detailed description
Lung injury and diaphragm injury incurred by mechanical ventilation have very serious adverse effects on patients with acute respiratory failure. Lung injury results from excessive mechanical stress and strain applied to the lung by the ventilator and/or respiratory muscles, while diaphragm injury results from either insufficient or excessive inspiratory effort.
The objective of this study is to investigate a new LDPV strategy designed to prevent both disuse-mediated and load-induced diaphragm injury, while also preventing excess global and regional mechanical stress and strain in the injured lung. To achieve these goals, the following specific targets to be met are: (1) respiratory muscle effort similar to that of healthy subjects breathing at rest, (2) lung stress within safe limits, and (3) clinically acceptable gas exchange.
Targets are assessed through measurements of global lung stress, tidal recruitment, inspiratory effort, diaphragm contractile effort and adequacy of respiratory muscle and systemic tissue perfusion. Measurements commence at enrollment and continue for 24 hours consecutively.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lower PEEP | Experimental | Procedure: Lung- and Diaphragm-Protective VentilationLung- and Diaphragm-Protective Ventilation - PEEP will be set at 8 cm H2O |
| Higher PEEP | Experimental | Procedure: Lung- and Diaphragm-Protective VentilationLung- and Diaphragm-Protective Ventilation - PEEP will be titrated to achieve end-expiratory PL = 2-3 cm H20 and at least 5 cm H2O greater than the level applied in the lower PEEP arm |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosed with acute hypoxemic respiratory failure
- PaO2:FiO2 ratio less than or equal to 300 mm Hg at time of screening
- Oral endotracheal intubation and mechanical ventilation
- Bilateral airspace opacities on chest radiograph or chest CT scan
Key exclusion criteria (4 listed)
- Liberation from mechanical ventilation is anticipated within 24 hours
- Intubated for traumatic brain injury or stroke
- Contraindication to esophageal catheterization
- Intracranial hypertension
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 |
|---|---|---|
| Lung- and Diaphragm-Protective VentilationAlso: LDPVVentilation and sedation will be progressively modified according to the LDPV algorithm to achieve targets. Patients will be crossed-over to the opposite PEEP strategy. LDPV titration will then be repeated to achieve LDPV targets. After establishing a combination of ventilation and sedation settings at which LDPV targets are achieved, the targets will be maintained over a 24-hour period. | Procedure or surgery | Higher PEEP, Lower PEEP |
Primary outcome
Rate of patients achieving and maintaining LDPV targets
Time frame: Assessed after achievement of LDPV targets for 24 hours
6 secondary outcomes
Inspiratory effort at lower and higher PEEP levels
Time frame: Assessed 10 minutes after PEEP and sedation are adjusted
Expiratory diaphragmatic effort at lower and higher PEEP levels
Time frame: Assessed 10 minutes after PEEP and sedation are adjusted
Lung stress and strain at low and high sweep gas flow rates
Time frame: Assessed 10 minutes after PEEP and sedation are adjusted
Inspiratory effort at low and high sweep gas flow rates
Time frame: Assessed 10 minutes after PEEP and sedation are adjusted
Sedative infusion rate at low and high sweep gas flow rates
Time frame: Assessed 10 minutes after PEEP and sedation are adjusted
Accuracy of artificial intelligence model in predicting patient outcomes
Time frame: Assessed after completing the 24-hour maintenance period
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 10 Dec 2024.
- Derived from this study: PubMed 36038890Dianti J, Fard S, Wong J, Chan TCY, Del Sorbo L, Fan E, Amato MBP, Granton J, Burry L, Reid WD, Zhang B, Ratano D, Keshavjee S, Slutsky AS, Brochard LJ, Ferguson ND, Goligher EC. Strategies for lung- and diaphragm-protective ventilation in acute hypoxemic respiratory failure: a physiological trial. Crit Care. 2022 Aug 29;26(1):259. doi: 10.1186/s13054-022-04123-9.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ewan Goligher, MD, PhD 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?
A Phase 1 study testing Lung- and Diaphragm-Protective Ventilation in people with Diaphragm Injury and 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 4 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: finished, as of the sponsor's last update on 10 Dec 2024. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Rate of patients achieving and maintaining LDPV targets (time frame: Assessed after achievement of LDPV targets for 24 hours). 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 NCT03612583, which also lists 1 linked publication.
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 10 Dec 2024.