ARDSMISMATCHED FRNCT05578742
V/Q Matching Variations With PEEP in ARDS According to Compliance-based Phenotypes (France)
A study testing PEEP increase and PEEP decrease in people with ARDS, run by University Hospital, Angers at 1 site in France.
Trial summary
This study aim to compare the effect of Positive End Expiratory Pressure (PEEP) on ventilation/perfusion mismatch in two phenotypes of patients with moderate-to-severe Acute Respiratory Distress Syndrome (ARDS), characterized by their respiratory system elastance (Ers). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ARDS
- What is being tested?
- PEEP increase and PEEP decrease
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteFrance
- Study dates
- 8 Feb 2024to Sep 2026
- Phase
- Interventional
- 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
Who may be able to join
- intubated patients with moderate and severe ARDS (Berlin definition, PaO2/FiO2 ≤200 mmHg at PEEP 5 cmH2O)
- undergoing deep sedation
- on controlled mechanical ventilation
- between 24 hours and 5 days after intubation.
Who cannot join
- age <18 years old; pregnancy
- patient undergoing legal protection
- contra-indications to EIT (e. g. severe chest trauma or wounds)
- pneumothorax; patient undergoing ECMO
- patient with BMI ≥35 kg/m2
- hemodynamic instability with MAP <60 mmHg despite vasopressors.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Angers Hospital
Angers, Maine et Loire, 49933
François Beloncle, MD, +33 2 41 58 65, Francois.Beloncle@chu-angers.fr
UH Angers DRCI UH Angers, +33 5 41 35 54 96, DRCI-Promotion-Interne@chu-angers.fr
About this study
Official title: Effect of PEEP on Ventilartion/Perfusion Ratios According to Different Phenotypes in Patients With ARDS (France)
This study aim to compare the effect of Positive End Expiratory Pressure (PEEP) on ventilation/perfusion mismatch in two phenotypes of patients with moderate-to-severe Acute Respiratory Distress Syndrome (ARDS), characterized by their respiratory system elastance (Ers). Ventilation/perfusion mismatch will be assessed by Electrical Impedance Tomography (EIT).
Read the detailed description
Acute Respiratory Distress Syndrome (ARDS) is characterized by hypoxemia caused by inflammatory lung injury. Recent studies showed an important variability in ARDS phenotypes . The recent COVID-19 crisis highlighted the presence of ARDS patients with severe hypoxemia and normal respiratory system compliance, and retrospective series confirmed the existence of this atypical ARDS pattern also in non-COVID etiologies.
The dissociation between mechanics and hypoxemia may be related to a specific diversity in the pattern of ventilation-perfusion matching (V/Q matching) among patients with normal compliance and ARDS. In patients with low compliance, V/Q mismatch may be characterized by right-to-left shunt, secondary to collapse of the gravity-dependent regions; while, in patients with normal compliance, V/Q mismatch may show a redistribution of blood flow to hypo-ventilated lung areas by larger dead space and impaired hypoxic vasoconstriction.
These differences may also influence the response to PEEP in terms of gas exchange and lung protection . It may also explain the failure for high PEEP levels to improve significantly mortality in the global ARDS population (i.e., with patients' selection only based on hypoxemia).
Electrical Impedance Tomography (EIT) is a device allowing to assess ventilation and perfusion distribution. Thus, EIT can be used to evaluate global and regional V/Q matching, and could be used to understand mechanisms of hypoxemia, especially in patients with normal mechanics and ARDS.
The aim of this study is to assess V/Q matching according to these different ARDS phenotypes, and to evaluate the effects of PEEP in each one.
- Conditions
- ARDS
- Being tested
- PEEP increase, PEEP decrease
- Keywords
- pulmonary perfusion, ventilation-perfusion mismatch, compliance, recruitability
- Medical subject headings
- Patient Compliance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PEEP increaseProcedure or surgery
Positive End Expiratory Pressure (PEEP) will be increased from 5 to 15 cmH2O.
PEEP decreaseProcedure or surgery
Positive End Expiratory Pressure (PEEP) will be decreased from 15 to 5 cmH2O.
| Study group | Role | What they receive |
|---|---|---|
| Strategy A: PEEP 15 cmH2O → PEEP 5 cmH2O | Experimental | Not described Receives: Procedure: PEEP decrease |
| Strategy B: PEEP 5 cmH2O → PEEP 15 cmH2O | Active comparator | Not described Receives: Procedure: PEEP increase |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in ventilation/perfusion mismatch between PEEP 5 and 15 cmH2O according to the two studied phenotypes
Ventilation/perfusion (V/Q) mismatch will be assessed by Electrical Impedance Tomography (EIT). Mismatch is expressed in %. Comparison between phenotype with higher and lower elastance will be performed.
Measured: immediately after each intervention
Secondary outcomes (10)
Difference in respiratory mechanics between PEEP 5 and 15 cmH2O according to the two studied phenotypes
Plateau pressure and total PEEP will be aggregated to compute driving pressure (Plateau pressure minus total PEEP, all in cmH2O). Respiratory system compliance will be computed by dividing tidal volume by driving pressure (in mL.cmH2O-1; respiratory system resistance will be computed as the inverse of compliance; all these values will be assessed and compared between the two PEEP levels. Comparison between phenotype with higher and lower elastance will be performed.
Measured: immediately after each intervention
Difference in oxygenation between PEEP 5 and 15 cmH2O according to the two studied phenotypes
PaO2 (in mmHg) will be assessed and compared between the two PEEP levels. Comparison between phenotype with higher and lower elastance will be performed.
Measured: immediately after each intervention
Difference in carbon clearance between PEEP 5 and 15 cmH2O according to the two studied phenotypes
PaCO2 (in mmHg) will be assessed and compared between the two PEEP levels. Ventilatory ratio (no unit) will be derived from the PaCO2 values. Comparison between phenotype with higher and lower elastance will be performed.
Measured: immediately after each intervention
Difference in dead space measured by capnometric volumetry between PEEP 5 and 15 cmH2O according to the two studied phenotypes
VCO2 (measured by Vcap, in mmHg) will be assessed and compared between the two PEEP levels. Comparison between phenotype with higher and lower elastance will be performed.
Measured: immediately after each intervention
Difference in dead space measured by calorimetry between PEEP 5 and 15 cmH2O according to the two studied phenotypes
VCO2 (measured by calorimetry, in mmHg) will be assessed and compared between the two PEEP levels. Comparison between phenotype with higher and lower elastance will be performed.
Measured: immediately after each intervention
Difference in venous oxygen saturation between PEEP 5 and 15 cmH2O according to the two studied phenotypes
SvO2 (in %) will be assessed and compared between the two PEEP levels. Comparison between phenotype with higher and lower elastance will be performed.
Measured: immediately after each intervention
Correlation between V/Q mismatch markers and recruitability
Recruitability will be assessed between 15 and 5 cmH2O by respiratory mechanics and EIT, as the recruited volumes value (in mL). R/I ratio will be derived from these data (no unit). V/Q mismatch will be computed by EIT, and expressed in %. Correlation will be performed by linear regression.
Measured: immediately after each intervention
Correlations between V/Q mismatch assessed by EIT and dead space markers
Dead space will be assessed by volumetric capnography (if available), venrtilatory ratio, and calorimetriy (if available). V/Q mismatch will be computed by EIT, and expressed in %. Correlation will be performed by linear regression.
Measured: immediately after each intervention
Correlations between V.Q mismacth and overdisension and lung collapsus
Overdistension (%) and lung collapsus (%) will be assessed during the Step 3, by EIT. These two values cannot be measured separately. V/Q mismatch will be computed by EIT, and expressed in %. Correlation will be performed by linear regression.
Measured: immediately after each intervention
Difference in stress index between PEEP 5 and 15 cmH2O according to the two studied phenotypes
stress index (no unit) will be assessed and compared between the two PEEP levels. Comparison between phenotype with higher and lower elastance will be performed.
Measured: immediately after each intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2022
- Study start8 Feb 2024
- Primary completionAug 2026 (estimated)
- Study completionSep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ARDSStudies of the same condition, open and under way.
- More trials run by University Hospital, AngersThe 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
- Model description
- Fifty patients will be enrolled, divided into 2 groups (n=26 each) according to a dynamic balanced sampling based on normalized respiratory system elastance (ERS) measured at PEEP 5 cmH2O with Vt 6-7 ml/kg PBW (\<2 cmH2O.mL-1.kg-1 vs. ≥2 cmH2O.mL-1.kg-1). Enrolment into each study group will be closed at 26 patients. Then, patients will be randomized and allocated to one of the following strategies: * Strategy A: PEEP 15 cmH2O → PEEP 5 cmH2O * Strategy B: PEEP 5 cmH2O → PEEP 15 cmH2O A parallel study will be conducted in Italy, to reach 50 more patients. Data will be shared between these two studies.
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Angers
- Sponsor type
- Other government
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05578742
- Sponsor's protocol ID
- 2022-A00649-34
- Acronym
- MISMATCHED FR
- Status last verified
- Dec 2025
- First submitted
- 27 Sep 2022
- Last updated
- 8 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of PEEP on Ventilartion/Perfusion Ratios According to Different Phenotypes in Patients With ARDS (France)
- ClinicalTrials.gov ID
- NCT05578742
- Acronym / sponsor ID
- MISMATCHED FR / 2022-A00649-34
- Conditions
- ARDS
- Keywords
- pulmonary perfusion, ventilation-perfusion mismatch, compliance, recruitability
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University Hospital, AngersOther government
- Study start
- 8 Feb 2024 (actual)
- Primary completion
- Aug 2026 (estimated)
- Study completion
- Sep 2026 (estimated)
- First posted
- 13 Oct 2022 (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 aim to compare the effect of Positive End Expiratory Pressure (PEEP) on ventilation/perfusion mismatch in two phenotypes of patients with moderate-to-severe Acute Respiratory Distress Syndrome (ARDS), characterized by their respiratory system elastance (Ers). Ventilation/perfusion mismatch will be assessed by Electrical Impedance Tomography (EIT).
Detailed description
Acute Respiratory Distress Syndrome (ARDS) is characterized by hypoxemia caused by inflammatory lung injury. Recent studies showed an important variability in ARDS phenotypes . The recent COVID-19 crisis highlighted the presence of ARDS patients with severe hypoxemia and normal respiratory system compliance, and retrospective series confirmed the existence of this atypical ARDS pattern also in non-COVID etiologies.
The dissociation between mechanics and hypoxemia may be related to a specific diversity in the pattern of ventilation-perfusion matching (V/Q matching) among patients with normal compliance and ARDS. In patients with low compliance, V/Q mismatch may be characterized by right-to-left shunt, secondary to collapse of the gravity-dependent regions; while, in patients with normal compliance, V/Q mismatch may show a redistribution of blood flow to hypo-ventilated lung areas by larger dead space and impaired hypoxic vasoconstriction.
These differences may also influence the response to PEEP in terms of gas exchange and lung protection . It may also explain the failure for high PEEP levels to improve significantly mortality in the global ARDS population (i.e., with patients' selection only based on hypoxemia).
Electrical Impedance Tomography (EIT) is a device allowing to assess ventilation and perfusion distribution. Thus, EIT can be used to evaluate global and regional V/Q matching, and could be used to understand mechanisms of hypoxemia, especially in patients with normal mechanics and ARDS.
The aim of this study is to assess V/Q matching according to these different ARDS phenotypes, and to evaluate the effects of PEEP in each one.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Fifty patients will be enrolled, divided into 2 groups (n=26 each) according to a dynamic balanced sampling based on normalized respiratory system elastance (ERS) measured at PEEP 5 cmH2O with Vt 6-7 ml/kg PBW (<2 cmH2O.mL-1.kg-1 vs. ≥2 cmH2O.mL-1.kg-1). Enrolment into each study group will be closed at 26 patients. Then, patients will be randomized and allocated to one of the following strategies: * Strategy A: PEEP 15 cmH2O → PEEP 5 cmH2O * Strategy B: PEEP 5 cmH2O → PEEP 15 cmH2O A parallel study will be conducted in Italy, to reach 50 more patients. Data will be shared between these two studies.
| Arm | Type | Receives |
|---|---|---|
| Strategy A: PEEP 15 cmH2O → PEEP 5 cmH2O | Experimental | Procedure: PEEP decrease |
| Strategy B: PEEP 5 cmH2O → PEEP 15 cmH2O | Active comparator | Procedure: PEEP increase |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- intubated patients with moderate and severe ARDS (Berlin definition, PaO2/FiO2 ≤200 mmHg at PEEP 5 cmH2O)
- undergoing deep sedation
- on controlled mechanical ventilation
- between 24 hours and 5 days after intubation.
Key exclusion criteria (6 listed)
- age <18 years old; pregnancy
- patient undergoing legal protection
- contra-indications to EIT (e. g. severe chest trauma or wounds)
- pneumothorax; patient undergoing ECMO
- patient with BMI ≥35 kg/m2
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 |
|---|---|---|
| PEEP increasePositive End Expiratory Pressure (PEEP) will be increased from 5 to 15 cmH2O. | Procedure or surgery | Strategy B: PEEP 5 cmH2O → PEEP 15 cmH2O |
| PEEP decreasePositive End Expiratory Pressure (PEEP) will be decreased from 15 to 5 cmH2O. | Procedure or surgery | Strategy A: PEEP 15 cmH2O → PEEP 5 cmH2O |
Primary outcome
Difference in ventilation/perfusion mismatch between PEEP 5 and 15 cmH2O according to the two studied phenotypes
Time frame: immediately after each intervention
Ventilation/perfusion (V/Q) mismatch will be assessed by Electrical Impedance Tomography (EIT). Mismatch is expressed in %. Comparison between phenotype with higher and lower elastance will be performed.
10 secondary outcomes
Difference in respiratory mechanics between PEEP 5 and 15 cmH2O according to the two studied phenotypes
Time frame: immediately after each intervention
Difference in oxygenation between PEEP 5 and 15 cmH2O according to the two studied phenotypes
Time frame: immediately after each intervention
Difference in carbon clearance between PEEP 5 and 15 cmH2O according to the two studied phenotypes
Time frame: immediately after each intervention
Difference in dead space measured by capnometric volumetry between PEEP 5 and 15 cmH2O according to the two studied phenotypes
Time frame: immediately after each intervention
Difference in dead space measured by calorimetry between PEEP 5 and 15 cmH2O according to the two studied phenotypes
Time frame: immediately after each intervention
Difference in venous oxygen saturation between PEEP 5 and 15 cmH2O according to the two studied phenotypes
Time frame: immediately after each intervention
Correlation between V/Q mismatch markers and recruitability
Time frame: immediately after each intervention
Correlations between V/Q mismatch assessed by EIT and dead space markers
Time frame: immediately after each intervention
Correlations between V.Q mismacth and overdisension and lung collapsus
Time frame: immediately after each intervention
Difference in stress index between PEEP 5 and 15 cmH2O according to the two studied phenotypes
Time frame: immediately after each intervention
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 8 Dec 2025.
- Individual participant dataSharing planned: Yes
Related trials for ARDS
Enrolling by invitation
Personalized Ventilator Settings for Patients on ECMO
Acute Respiratory Distress Syndrome (ARDS), Extracorporeal Membrane Oxygenation
Not yet recruitingObservational study
Development and Multicenter Validation of an Explainable System for Neonatal ARDS-Compatible Phenotyping
Acute Respiratory Distress Syndrome
RecruitingObservational study
Assessment of Blood Viscosity in ARDS (Acute Respiratory Distress Syndrome)
ARDS
Recruiting
Comparing Surfactant Administration Through Supraglottic Airway and Thin Catheter for Preterm Infants
Surfactant, Respiratory Distress Syndrome (Neonatal)
Recruiting
REspiratory MEchanics for Delivering Individualised Exogenous Surfactant
Respiratory Distress Syndrome in Premature Infant
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?
A study testing PEEP increase and PEEP decrease in people with ARDS, run by University Hospital, Angers at 1 site in France.
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 6 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 8 Dec 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 France. 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 François Beloncle, MD (+33 241 35 58 65, francois.Francois.Beloncle@chu-angers.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in ventilation/perfusion mismatch between PEEP 5 and 15 cmH2O according to the two studied phenotypes (time frame: immediately after each intervention). 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 8 Dec 2025.