Respiratory FailureINFLATE-ICUNCT07188038
The Impact of Low Versus High Positive End-expiratory Pressure on Diaphragm Function, Ventilation Efficiency, and Lung Mechanics
A study testing Low positive end-expiratory pressure, Medium positive end-expiratory pressure and High positive end-expiratory pressure in people with Respiratory Failure and ARDS (Acute Respiratory Distress Syndrome), run by Vastra Gotaland Region at 2 sites in Sweden.
Trial summary
The goal of this interventional study is to evaluate the effect of different positive end-expiratory pressures (PEEP) on lung and diaphragm function in patients mechanically ventilated with pressure support ventilation in the intensive care unit. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Respiratory Failure, ARDS (Acute Respiratory Distress Syndrome), Pneumonia
- What is being tested?
- Low positive end-expiratory pressure, Medium positive end-expiratory pressure and High positive end-expiratory pressure
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 2 sitesSweden
- Study dates
- 31 Aug 2026to 31 Dec 2027
- Phase
- Interventional
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
- Mechanical ventilation with pressure support or mechanical ventilation with possibility to transition to pressure support
- Oxygen requirement ≤ 50%
- Pressure support ≤ 12 cmH2O
- PEEP ≤ 12 cmH2O
- Age ≥ 18 years
- Adequate intravascular volume status
Who cannot join
- Circulatory instability
- Brain death diagnosis/brain death evaluation
- Norepinephrine dose > 0.4 µg/kg/min
- Muscle relaxation administered within 2 hours
- Pregnancy
- Contraindication to esophageal catheterization (e.g., esophageal varices)
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- Conditions with increased risk of pneumothorax (such as severe COPD (Chronic Obstructive Pulmonary Disease) or extensive emphysema)
- Untreated pneumothorax
- Symptomatic airway obstruction
- Discontinuation criteria during ongoing study intervention:
- Heart rate > 120 beats/min
- Systolic blood pressure > 180 mmHg
- Inspired oxygen fraction > 70%
- Respiratory rate > 35/min
- RASS (Richmond Agitation Sedation Scale) ≥ 2
- Doubling of norepinephrine dose or increase of norepinephrine dose to > 0.5 µg/kg/min to maintain mean arterial pressure
- Bradycardia < 45 beats/min
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Per Persson contact
Sweden2 sites, 2 recruiting
- Recruiting
Central intensivvårdsavdelning, Sahlgrenska University Hospital
Gothenburg, Västra Götaland County, 413 45
Hannes Widing, 0046703957374, hannes.widing@vgregion.se
Hannes Widing
- Not yet recruiting
Thorax intensivvårdsavdelning, Område 6, Sahlgrenska University Hospital, Västra Götalandsregionen
Gothenburg, Västra Götaland County, 413 45
Viktor Erbring, 0046706456664, viktor.erbring@vgregion.se
About this study
Official title: The Impact of Low Versus High Positive End-Expiratory Pressure on Diaphragm Function, Ventilation Efficiency, and Lung Mechanics During Pressure Support Ventilation: A Randomized Interventional Crossover Study
The goal of this interventional study is to evaluate the effect of different positive end-expiratory pressures (PEEP) on lung and diaphragm function in patients mechanically ventilated with pressure support ventilation in the intensive care unit. The main questions aim to answer:
Does higher PEEP level affect diaphragm contractions and ventilatory efficiency? Does higher PEEP level limit inspiratory efforts? Does higher PEEP level affect lung compliance?
Read more
The participants will be subjected to three different PEEP levels during pressure support ventilation:
Low PEEP (4 cmH2O), Medium PEEP (10 cmH2O), High PEEP (16 cmH2O).
The lung and diaphragm function will be evaluated using high-resolution esophageal manometry, electrical activity of the diaphragm, external diaphragm ultrasound and spirometric ventilator data.
- Conditions
- Respiratory Failure, ARDS (Acute Respiratory Distress Syndrome), Pneumonia, Respiratory Insufficiency
- Being tested
- Low positive end-expiratory pressure, Medium positive end-expiratory pressure, High positive end-expiratory pressure
- Keywords
- Positive end-expiratory pressure, PEEP, pressure support ventilation, assisted breathing, Inspiratory effort, Inspiratory drive, Ventilation efficiency, Diaphragm
- Medical subject headings
- Respiratory Insufficiency, Acute Lung Injury, Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low positive end-expiratory pressureProcedure or surgery
Low (4 cmH2O) positive end-expiratory pressure (PEEP) will be applied during pressure support ventilation. The PEEP level will be kept for 10 minutes prior to data acquisition.
Medium positive end-expiratory pressureProcedure or surgery
Medium (10 cmH2O) positive end-expiratory pressure (PEEP) will be applied during pressure support ventilation. The PEEP level will be kept for 10 minutes prior to data acquisition.
High positive end-expiratory pressureProcedure or surgery
High(16 cmH2O) positive end-expiratory pressure (PEEP) will be applied during pressure support ventilation. The PEEP level will be kept for 10 minutes prior to data acquisition.
| Study group | Role | What they receive |
|---|---|---|
| Low PEEP | Experimental | Low positive end-expiratory pressure (4 cmH2O) Receives: Procedure: Low positive end-expiratory pressure |
| Medium PEEP | Experimental | Medium positive end-expiratory pressure (10 cmH2O) Receives: Procedure: Medium positive end-expiratory pressure |
| High PEEP | Experimental | High positive end-expiratory pressure (16 cmH2O) Receives: Procedure: High positive end-expiratory pressure |
What is being measured
The primary outcome is the main question the study is designed to answer.
Inspiratory effort
Inspiratory effort will be measured by the tidal change in esophageal pressure (in cmH2O) during assisted breathing. The esophageal pressure will be measured using a high-resolution manometry catheter. The change from expiratory to inspiratory esophageal pressure will represent the tidal change and be used to estimate the inspiratory effort.
Measured: Measured during 5 uninterrupted breaths 10 minutes after application of interventional PEEP level
Inspiratory drive
The electric activity of the diaphragm (Eadi) will be measured using a NAVA (neurally adjusted ventilatory assist) catheter. The change from end-expiratory to inspiratory Eadi will be calculated. This represents the inspiratory drive. The Eadi will be measured in Voltage.
Measured: Measured during 5 uninterrupted breaths 10 minutes after application of interventional PEEP level
Effort-to-drive ratio
The effort-to-drive ratio (EDR) will be calculated as the inspiratory effort (tidal change in esophageal pressure) divided by the inspiratory drive (tidal change in electric activity of the diaphragm).
Measured: Calculated from the measures collected 10 minutes after application of interventional PEEP level
Neuromechanical efficiency
The neuromechanical efficiency will be calculated as the change in airway pressure during an occlusion test (Pocc) (measured from end-expiration to maximum negative pressure during the occlusion manoeuvre) divided by the inspiratory change in electric activity of the diaphragm (from end-expiration to inspiration).
Measured: Calculated from the measures collected during the occlusion manoeuvre performed 10-15 minutes after application of interventional PEEP level
Thickening fraction of the diaphragm (TFdi)
Measured by ultrasound at the right hemidiaphragm. The thickening fraction of the diaphragm (TFdi) will be calculated as [ (end-inspiratory diaphragm thickness - end-expiratory diaphragm thickness) / end-expiratory diaphragm thickness) ].
Measured: Measured 10 minutes after application of interventional PEEP level
Transpulmonary driving pressure
Change in transpulmonary pressure ( airway pressure - esophageal pressure) from end-expiration to end-inspiration will be calculated using ventilator data and high-resolution manometry
Measured: Measured during 5 breaths 10 minutes after application of interventional PEEP level
Occlusion pressure
The airway pressure drop from end-expiration to minimum pressure during an occlusion manoeuvre will be measured using the ventilator. The pressure drop indicates the inspiratory effort. It will be measured in cmH2O.
Measured: The occlusion pressure will be measured during an occlusion manoeuvre performed 10-15 minutes after application of interventional PEEP level.
Secondary outcomes (5)
Airway driving pressure
Difference in airway pressure between end-expiration and during an inspiratory hold will be calculated from the ventilator data.
Measured: Measured during an inspiratory hold performed 10-15 minutes after application of interventional PEEP level
Lung compliance
Lung compliance will be calculated as the tidal volume divided by the change in transpulmonary pressure from end-expiration to end-inspiration.
Measured: Measured during an inspiratory hold performed 10 - 15 minutes after application of interventional PEEP level
Thickening fraction of the expiratory abdominal muscles (TFabd)
The abdominal muscles will be visualized by ultrasound in the anterior axillary line, midway between the inferior border of the ribcage and the iliac crest. The thickening fraction will be calculated as [(expiratory thickness - end-inspiratory thickness) / end-inspiratory thickness ].
Measured: Measured 10 minutes after application of interventional PEEP level
Oxygenation
The PFI (PaO2/FiO2 ratio) will be calculated as arterial PaO2 (partial pressure of oxygen) divided by the FiO2 (fraction of inspired oxygen)
Measured: The blood gas will be collected 10 minutes after application of interventional PEEP level
Respiratory system compliance
The respiratory system compliance will be calculated as the tidal volume divided by the airway driving pressure during an inspiratory hold.
Measured: Measured during an inspiratory hold manoeuvre performed 10-15 minutes after the application of interventional PEEP level.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2025
- Study start31 Aug 2026
- Primary completion31 Jul 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Respiratory 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
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized interventional crossover study
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vastra Gotaland Region
- Sponsor type
- Other government
- Collaborators
- Sahlgrenska University Hospital, Göteborg University
- Responsible party
- Sponsor
- Investigators
- Hannes Widing, Principal investigator, Anesthesia and intensive care medicine, Område 5, Sahlgrenska University hospital, Västra Götalandsregionen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07188038
- Sponsor's protocol ID
- 2025-01286-01
- Other IDs
- 2025
- Acronym
- INFLATE-ICU
- Status last verified
- Sep 2026
- First submitted
- 1 Sep 2025
- Last updated
- 2 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The acquired swedish ethical permit does not allow for the sharing of data to international researcher without a confidentiality review or the application of a new ethical permit