Acute Respiratory Distress SyndromeALIVENCT03589482
Assessing Lung Inhomogeneity During Ventilation for Acute Hypoxemic Respiratory Failure
A study testing Electrical Impedance Tomography and ExPRESS-derived PEEP level in people with Acute Respiratory Distress Syndrome and Mechanical Ventilation Pressure High, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
Mechanical ventilation can cause damage by overstretching the lungs, especially when the lungs are collapsed or edematous. Raising ventilator pressures can reduce lung collapse and this can prevent overstretching from mechanical ventilation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Respiratory Distress Syndrome, Mechanical Ventilation Pressure High, Hypoxemic Respiratory Failure
- What is being tested?
- Electrical Impedance Tomography and ExPRESS-derived PEEP level
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- 1 Mar 2019to 31 Aug 2021
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Acute (≤7 days) hypoxemia with PaO2:FiO2 ratio less than or equal to 200 mm Hg
- Oral endotracheal intubation and mechanical ventilation
- Bilateral airspace opacities on chest radiograph or CT
Who cannot join
- Contraindication to EIT electrode placement (burns, chest wall bandaging limiting electrode placement)
- Contraindication to esophageal catheter placement (recent upper GI surgery, actively bleeding esophageal varices)
- Respiratory failure predominantly due to cardiogenic cause or fluid overload
- Ongoing hemodynamic instability (requiring 2 vasopressor agents by continuous infusion AND rising vasopressor infusion rate requirements in the previous 8 hours)
- Ongoing ventilatory instability (P/F < 70 mm Hg, pH < 7.2; ventilator driving pressures, PEEP, or FiO2 increasing by more than 25% in previous 30 minutes)
- Intracranial hypertension (suspected or diagnosed by medical team)
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- Known or suspected pneumothorax recognized within previous 72 hours
- Bronchopleural fistula
- Bridge to lung transplant
- Recent lung transplantation (within previous 6 weeks)
- Attending physician deems the transient application of high airway pressures (>40 cm H2O) to be unsafe
Trial locations and contacts
1 site in 1 country.
About this study
Mechanical ventilation can cause damage by overstretching the lungs, especially when the lungs are collapsed or edematous. Raising ventilator pressures can reduce lung collapse and this can prevent overstretching from mechanical ventilation. It remains uncertain how much pressure (PEEP - positive end-expiratory pressure) should be used on the ventilator and how to identify patients who will benefit from higher ventilator pressures vs. lower ventilator pressures. The investigators are using a unique new imaging technology, electrical impedance tomography (EIT), to study this problem and to determine the safest and most effective ventilator pressure level. The results of this study will inform future trials of higher vs. lower PEEP strategies in mechanically ventilated patients.
Read the detailed description
Patients participating in this physiological cross-over randomized trial will undergo a series of PEEP maneuvers designed to assess lung recruitability, PEEP responsiveness, and optimal PEEP. EIT imaging and esophageal manometry will be employed throughout the protocol to quantify the effect of PEEP on lung function. Patients will be randomized to be ventilated at PEEP levels supplied by the ExPRESS strategy or by the EIT hyperdistention/collapse algorithm. The biological response will be assessed by measuring serum cytokines.
- Conditions
- Acute Respiratory Distress Syndrome, Mechanical Ventilation Pressure High, Hypoxemic Respiratory Failure
- Being tested
- Electrical Impedance Tomography, ExPRESS-derived PEEP level
- Medical subject headings
- Respiratory Distress Syndrome, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Electrical Impedance TomographyDevice
Electrical impedance tomography (EIT) is a new technique that enables real-time visualization of the distribution of ventilation at the bedside. This technique allows clinicians and investigators to immediately determine how applying higher or lower PEEP levels affect stress and strain in the lung. The investigators propose to apply this new technique to test a strategy for finding the optimal level of PEEP that prevents lung injury and improves outcomes in critically ill patients.
ExPRESS-derived PEEP levelOther
The ExPRESS algorithm is a traditional approach to selecting PEEP based on respiratory mechanics.
| Study group | Role | What they receive |
|---|---|---|
| EIT algorithm | Experimental | Patients randomized to this arm will be ventilated at the PEEP level selected by the EIT algorithm, which selects a PEEP at which both collapse and hyperdistention are minimized. Receives: Device: Electrical Impedance Tomography |
| ExPRESS algorithm | Active comparator | Patients randomized to this arm will be ventilated at the PEEP level selected by the ExPRESS algorithm, which is a method that targets a tidal volume of 6 ml/kg predicted body weight and then titrates PEEP until plateau airway pressure reaches 28 cm H2O. Receives: Other: ExPRESS-derived PEEP level |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intratidal ventilation heterogeneity
A measure of variation in the distribution of ventilation throughout the lung as detected by electrical impedance tomography
Measured: Assessed after completion of 3 hours on randomized strategy (EIT vs ExPRESS)
Secondary outcomes (3)
Difference in the optimal PEEP levels identified by several different PEEP titration strategies
Compare the relative degree of agreement or disparity between PEEP levels recommended by different PEEP titration strategies
Measured: Assessed immediately after completion of decremental PEEP titration procedure
Change in ratio of partial pressure of oxygen (PaO2) to inspired fraction of oxygen (FiO2) ratio following a standardized increased in PEEP
Measurement of changes in oxygenation by PaO2/FiO2 ratio due to PEEP
Measured: Assessed 10 minutes after step PEEP increase from 6-8 to 16-18 cm H2O
Respiratory mechanics (transpulmonary driving pressure)
The swing in transpulmonary pressure during inspiration, a measure of dynamic lung stress
Measured: Assessed after completing 3 hours on the randomized PEEP strategy (EIT vs ExPRESS)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2018
- Study start1 Mar 2019
- Primary completion31 Mar 2021
- Study completion31 Aug 2021
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 Acute Respiratory Distress SyndromeStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 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
- NCT03589482
- Sponsor's protocol ID
- 18-6091
- Other IDs
- 17-6226
- Acronym
- ALIVE
- Status last verified
- Aug 2020
- First submitted
- 6 Apr 2018
- Last updated
- 21 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Santa Cruz R, Villarejo F, Irrazabal C, Ciapponi A. High versus low positive end-expiratory pressure (PEEP) levels for mechanically ventilated adult patients with acute lung injury and acute respiratory distress syndrome. Cochrane Database Syst Rev. 2021 Mar 30;3(3):CD009098. doi: 10.1002/14651858.CD009098.pub3.
PubMed 33784416
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessing Lung Inhomogeneity During Ventilation for Acute Hypoxemic Respiratory Failure
- ClinicalTrials.gov ID
- NCT03589482
- Acronym / sponsor ID
- ALIVE / 18-6091
- Conditions
- Acute Respiratory Distress Syndrome, Mechanical Ventilation Pressure High, Hypoxemic Respiratory Failure
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- 1 Mar 2019 (actual)
- Primary completion
- 31 Mar 2021 (actual)
- Study completion
- 31 Aug 2021 (actual)
- First posted
- 18 Jul 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.
Mechanical ventilation can cause damage by overstretching the lungs, especially when the lungs are collapsed or edematous. Raising ventilator pressures can reduce lung collapse and this can prevent overstretching from mechanical ventilation. It remains uncertain how much pressure (PEEP - positive end-expiratory pressure) should be used on the ventilator and how to identify patients who will benefit from higher ventilator pressures vs. lower ventilator pressures. The investigators are using a unique new imaging technology, electrical impedance tomography (EIT), to study this problem and to determine the safest and most effective ventilator pressure level. The results of this study will inform future trials of higher vs. lower PEEP strategies in mechanically ventilated patients.
Detailed description
Patients participating in this physiological cross-over randomized trial will undergo a series of PEEP maneuvers designed to assess lung recruitability, PEEP responsiveness, and optimal PEEP. EIT imaging and esophageal manometry will be employed throughout the protocol to quantify the effect of PEEP on lung function. Patients will be randomized to be ventilated at PEEP levels supplied by the ExPRESS strategy or by the EIT hyperdistention/collapse algorithm. The biological response will be assessed by measuring serum cytokines.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| EIT algorithm | Experimental | Device: Electrical Impedance TomographyPatients randomized to this arm will be ventilated at the PEEP level selected by the EIT algorithm, which selects a PEEP at which both collapse and hyperdistention are minimized. |
| ExPRESS algorithm | Active comparator | Other: ExPRESS-derived PEEP levelPatients randomized to this arm will be ventilated at the PEEP level selected by the ExPRESS algorithm, which is a method that targets a tidal volume of 6 ml/kg predicted body weight and then titrates PEEP until plateau airway pressure reaches 28 cm H2O. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Acute (≤7 days) hypoxemia with PaO2:FiO2 ratio less than or equal to 200 mm Hg
- Oral endotracheal intubation and mechanical ventilation
- Bilateral airspace opacities on chest radiograph or CT
Key exclusion criteria (11 listed)
- Contraindication to EIT electrode placement (burns, chest wall bandaging limiting electrode placement)
- Contraindication to esophageal catheter placement (recent upper GI surgery, actively bleeding esophageal varices)
- Respiratory failure predominantly due to cardiogenic cause or fluid overload
- Ongoing hemodynamic instability (requiring 2 vasopressor agents by continuous infusion AND rising vasopressor infusion rate requirements in the previous 8 hours)
- Ongoing ventilatory instability (P/F < 70 mm Hg, pH < 7.2; ventilator driving pressures, PEEP, or FiO2 increasing by more than 25% in previous 30 minutes)
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 |
|---|---|---|
| Electrical Impedance TomographyElectrical impedance tomography (EIT) is a new technique that enables real-time visualization of the distribution of ventilation at the bedside. This technique allows clinicians and investigators to immediately determine how applying higher or lower PEEP levels affect stress and strain in the lung. The investigators propose to apply this new technique to test a strategy for finding the optimal level of PEEP that prevents lung injury and improves outcomes in critically ill patients. | Device | EIT algorithm |
| ExPRESS-derived PEEP levelThe ExPRESS algorithm is a traditional approach to selecting PEEP based on respiratory mechanics. | Other | ExPRESS algorithm |
Primary outcome
Intratidal ventilation heterogeneity
Time frame: Assessed after completion of 3 hours on randomized strategy (EIT vs ExPRESS)
A measure of variation in the distribution of ventilation throughout the lung as detected by electrical impedance tomography
3 secondary outcomes
Difference in the optimal PEEP levels identified by several different PEEP titration strategies
Time frame: Assessed immediately after completion of decremental PEEP titration procedure
Change in ratio of partial pressure of oxygen (PaO2) to inspired fraction of oxygen (FiO2) ratio following a standardized increased in PEEP
Time frame: Assessed 10 minutes after step PEEP increase from 6-8 to 16-18 cm H2O
Respiratory mechanics (transpulmonary driving pressure)
Time frame: Assessed after completing 3 hours on the randomized PEEP strategy (EIT vs ExPRESS)
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 21 Nov 2023.
- Derived from this study: PubMed 33784416Santa Cruz R, Villarejo F, Irrazabal C, Ciapponi A. High versus low positive end-expiratory pressure (PEEP) levels for mechanically ventilated adult patients with acute lung injury and acute respiratory distress syndrome. Cochrane Database Syst Rev. 2021 Mar 30;3(3):CD009098. doi: 10.1002/14651858.CD009098.pub3.
- 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 study testing Electrical Impedance Tomography and ExPRESS-derived PEEP level in people with Acute Respiratory Distress Syndrome and Mechanical Ventilation Pressure High, 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 3 inclusion and 11 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 21 Nov 2023. 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?
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?
Intratidal ventilation heterogeneity (time frame: Assessed after completion of 3 hours on randomized strategy (EIT vs ExPRESS)). 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 NCT03589482, 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 21 Nov 2023.