Acute Respiratory Distress Syndrome (ARDS)NOVAEOLIANCT07516665
Ultraprotective Lung Ventilation With Respiratory Extracorporeal Life Support for ARDS
A study testing ECLS in people with Acute Respiratory Distress Syndrome (ARDS), run by Assistance Publique - Hôpitaux de Paris.
Trial summary
Acute respiratory distress syndrome (ARDS) accounts for approximately 10% of all ICU admissions and 23% of patients requiring mechanical ventilation (MV). Despite advances in care, hospital mortality remains high, ranging from 34% in mild cases to 46% in severe ARDS. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Respiratory Distress Syndrome (ARDS)
- What is being tested?
- ECLS
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 290 participants
- Where
- No sites listed yet
- Study dates
- 11 May 2026to Aug 2028
- 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
- Intubation and Invasive mechanical ventilation ≤ 7 days
- Presence of all of the following conditions for ≤48 hours:
- 80 ≤ PaO2/FiO2 ≤300 with PEEP >5 cmH2O
- Bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules
- Respiratory failure not fully explained by cardiac failure or fluid overload
- One of the following criteria (with Vt set at 6 mL/kg PBW):
Show all 10Show fewer
- DeltaP ≥15 cm H2O OR
- Ventilatory ratio ≥2.2
- Signed Informed consent from a close relative or surrogate or a family member. According to the specifications of emergency inclusion, randomization without the close relative/surrogate consent could be performed if the patient is unable to give his/ger consent and when the close relative/surrogate/family member are absent. Close relative/surrogate/family member consent will be asked as soon as possible after randomization. The patient will be asked as soon as possible to give his/her consent for the continuation of the trial when his/her condition will allow.
- Social security registration (AME excluded)
Who cannot join
- Age <18 years
- Pregnancy or breastfeeding
- Catheter access to femoral vein or jugular vein impossible
- Expected duration of mechanical ventilation < 48 hours
- Chronic restrictive or obstructive (COPD) respiratory insufficiency with home ventilation or oxygen therapy
- Currently receiving ECLS therapy
Show all 15Show fewer
- Severe cardiac failure or ongoing acute coronary syndrome
- Heparin-induced thrombocytopenia
- Severe underlying pre-existing condition with expected six-month mortality >50%
- Contraindication for systemic anticoagulation (including platelet count <50G/L)
- Patient moribund, decision to limit therapeutic interventions
- Acute brain injury or irreversible neurological pathology
- Bone marrow transplantation within the last 1 year
- Actual body weight exceeding 1 kg per centimeter of height
- Prior enrolment in the trial
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Acute respiratory distress syndrome (ARDS) accounts for approximately 10% of all ICU admissions and 23% of patients requiring mechanical ventilation (MV). Despite advances in care, hospital mortality remains high, ranging from 34% in mild cases to 46% in severe ARDS. Positive-pressure MV remains the cornerstone of ARDS management. However, when excessive stress and strain are applied to the lung parenchyma, it can exacerbate lung injury, leading to ventilator-induced lung injury (VILI). VILI substantially contributes to morbidity and mortality in ARDS. Strategies that reduce tidal volume (Vt), driving pressure (ΔP, defined as plateau pressure minus PEEP), and respiratory rate (RR) can lower the mechanical power (PowerRS), i.e., the energy delivered to the lungs by the ventilator. This reduction in pulmonary stress and strain may lessen VILI and potentially improve survival. Nonetheless, reducing Vt to <6 ml/kg in order to achieve plateau pressures <23-25 cm H₂O, driving pressures <9-11 cm H₂O, and RR <15-20/min can result in severe hypercapnia. This, in turn, may increase intracranial pressure, promote pulmonary hypertension, impair myocardial contractility, reduce renal perfusion, and trigger endogenous catecholamine release. Thus, such "ultraprotective" MV strategies are not feasible for most ARDS patients managed with conventional ventilation. The neutral findings of the REST trial further suggested that low-flow extracorporeal CO₂ removal (ECCO₂R) devices may provide insufficient CO₂ clearance to enable ultraprotective ventilation while adequately controlling respiratory acidosis. Moreover, since partial lung derecruitment may occur with substantial Vt reduction, extracorporeal membrane oxygenation (ECMO) may be necessary, particularly in patients with PaO₂/FiO₂ <120-130 at the time of Vt reduction. Therefore, respiratory extracorporeal life support (ECLS)-ranging from high-flow ECCO₂R to mid-flow venovenous ECMO (VV-ECMO)-can be employed in this setting. These modalities facilitate further reductions in ventilatory intensity while ensuring adequate oxygenation and CO₂ removal.
- Being tested
- ECLS
- Keywords
- ECLS, Acute Respiratory Distress Syndorme (ARDS)
- Medical subject headings
- Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ECLSProcedure or surgery
- ECLS catheters inserted, and EC LS initiated no later than 12h after randomization
- Vt decreased to a min of 3 ml/kg PBW (by 0.5ml/kg every 30 min) to reach ΔP 9 -11 cmH2O and at least 5 cm H2O ΔP decrease
- PEEP adjusted to keep the same mean airway pressure
- Pump outflow set at 2-4 L/min , based on the need of blood oxygenation
- RR decreased to a min of 12/min with gas flowrate adjusted to maintain PaCO2 45 mmHg.
- Protocolized weaning of ECLS
| Study group | Role | What they receive |
|---|---|---|
| Expérimental : ECLS | Experimental | * ECLS catheter s inserted, and EC LS initiated no later than 12h after randomization
* Vt decreased to a min of 3 ml/kg PBW (by 0.5ml/kg every 30 min) to reach ΔP 9-11 cm H2O and at least 5 cm H 2 O ΔP decrease
* PEEP adjusted to keep the same mean airway pressure
* Pump outflow set at 2-4 L/min , based on the need of blood oxygenation
* RR decreased to a min of 12/min with gas flow rate adjusted to maintain PaCO2 45 mmHg.
* Protocolized weaning of ECLS Receives: Procedure: ECLS |
| Control : Conventional Treatment Arm | No intervention | * Conventional management of ARDS * Ventilatory settings: * Volume assist control mode, * VT 6 ml/kg of predicted body weight * PEEP adjusted for Pplateau 28 29 cmH2O ; * FiO2 for 88%≤SaO2≤95% or 55 mmHg≤PaO2≤80 mm Hg * RR up to 35/mn, for a PaCO2 resulting in 7.30<pH<7.42 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hierarchical criterion assessed at day 30, including all-cause mortality followed by the number of days free from MV at day 30, and calculated in such a manner that death constitutes a worse outcome than duration of ventilation.
Each patient is compared with every other patient in the study and assigned a score (tie: 0, win: +1, loss: -1) for each pairwise comparison based on whom fared better.
- If one patient survived at day 30 and the other did not, scores of +1 and -1 will be assigned, respectively, for that pairwise comparison. If both patients in the pairwise comparison survived at day 30, the assigned score will depend on which patient had more days free from MV at day 30: the patient with more days off MV will receive a score of +1, while the patient with fewer days will receive a score of -1. If both patients survived and had the same number of days off MV, or if both patients died, they will be both assigned a score of 0 for that pairwise comparison. For each patient, scores for all pairwise comparisons will be summed, resulting in a cumulative score.
Measured: Day 30
Secondary outcomes (27)
Mortality
Measured: Day 30, Day 60, Day 90
Duration of mechanical ventilation
Measured: From inclusion to Day 30, from inclusion to Day 60
Number of mechanical ventilation free days
Measured: Day 30, Day 60
Duration of catecholamine hemodynamic support
Measured: From inclusion to Day 30, from inclusion to Day 60
Number of catecholamine hemodynamic support free days
Measured: Day 30, Day 60
Number of organ failure(s) free days
Measured: Day 30, Day 60
Number of renal replacement therapy free days
Measured: Day 30, Day 60
Durations of ICU stay
Measured: Day 90
Duration of hospitalization
Measured: Day 90
Proportion of patients with Pneumothorax
Measured: Day 30, Day 60
Proportion of patient with rescue procedures and therapies for severe ARDS
Measured: Day 90
Incidence of pump malfunction related to ECLS
Measured: Day 90
Incidence of clotting related to ECLS
Measured: Day 90
Incidence of air embolism related to ECLS
Measured: Day 90
Incidence of hemolysis related to ECLS
Measured: Day 90
Incidence of vein perforation related to ECLS
Measured: Day 90
Incidence of significant bleeding (related to cannula insertion, at canula site) related to ECLS
Measured: Day 90
Incidence of major hemorrhage related to ECLS
Measured: Day 90
Incidence of infection at cannula site related to ECLS
Measured: Day 90
Incidence of thromboembolic events related to ECLS
Measured: Day 90
Incidence of stroke related to ECLS
Measured: Day 90
Incidence of thrombocytopenia related to ECLS
Measured: Day 90
Incidence of hypofibrinogenemia related to ECLS
Measured: Day 90
Number of packed red blood cells transfused
Measured: Day 90
Incidence of ventilator-associated pneumonia
Measured: From inclusion to Day 30, form inclusion to Day 60
Number of days without organ failure(s), defined with the SOFA score
Measured: Day 30, Day 60
Number of days without renal replacement therapy
Measured: Day 30, Day 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2026
- Study start11 May 2026 (estimated)
- Primary completionJun 2028 (estimated)
- Study completionAug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Respiratory Distress Syndrome (ARDS)Studies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Multicenter, prospective, randomized, comparative open trial
- Masking
- None (open label)
- Enrolment
- 290 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07516665
- Sponsor's protocol ID
- APHP240924
- Other IDs
- IDRCB number
- Acronym
- NOVAEOLIA
- Status last verified
- Apr 2026
- First submitted
- 1 Apr 2026
- Last updated
- 14 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients. Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ultraprotective Lung Ventilation With Respiratory Extracorporeal Life Support for ARDS
- ClinicalTrials.gov ID
- NCT07516665
- Acronym / sponsor ID
- NOVAEOLIA / APHP240924
- Keywords
- ECLS, Acute Respiratory Distress Syndorme (ARDS)
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 290 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 11 May 2026 (estimated)
- Primary completion
- Jun 2028 (estimated)
- Study completion
- Aug 2028 (estimated)
- First posted
- 8 Apr 2026 (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.
Acute respiratory distress syndrome (ARDS) accounts for approximately 10% of all ICU admissions and 23% of patients requiring mechanical ventilation (MV). Despite advances in care, hospital mortality remains high, ranging from 34% in mild cases to 46% in severe ARDS. Positive-pressure MV remains the cornerstone of ARDS management. However, when excessive stress and strain are applied to the lung parenchyma, it can exacerbate lung injury, leading to ventilator-induced lung injury (VILI). VILI substantially contributes to morbidity and mortality in ARDS. Strategies that reduce tidal volume (Vt), driving pressure (ΔP, defined as plateau pressure minus PEEP), and respiratory rate (RR) can lower the mechanical power (PowerRS), i.e., the energy delivered to the lungs by the ventilator. This reduction in pulmonary stress and strain may lessen VILI and potentially improve survival. Nonetheless, reducing Vt to <6 ml/kg in order to achieve plateau pressures <23-25 cm H₂O, driving pressures <9-11 cm H₂O, and RR <15-20/min can result in severe hypercapnia. This, in turn, may increase intracranial pressure, promote pulmonary hypertension, impair myocardial contractility, reduce renal perfusion, and trigger endogenous catecholamine release. Thus, such "ultraprotective" MV strategies are not feasible for most ARDS patients managed with conventional ventilation. The neutral findings of the REST trial further suggested that low-flow extracorporeal CO₂ removal (ECCO₂R) devices may provide insufficient CO₂ clearance to enable ultraprotective ventilation while adequately controlling respiratory acidosis. Moreover, since partial lung derecruitment may occur with substantial Vt reduction, extracorporeal membrane oxygenation (ECMO) may be necessary, particularly in patients with PaO₂/FiO₂ <120-130 at the time of Vt reduction. Therefore, respiratory extracorporeal life support (ECLS)-ranging from high-flow ECCO₂R to mid-flow venovenous ECMO (VV-ECMO)-can be employed in this setting. These modalities facilitate further reductions in ventilatory intensity while ensuring adequate oxygenation and CO₂ removal.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Multicenter, prospective, randomized, comparative open trial
| Arm | Type | Receives |
|---|---|---|
| Expérimental : ECLS | Experimental | Procedure: ECLS* ECLS catheter s inserted, and EC LS initiated no later than 12h after randomization * Vt decreased to a min of 3 ml/kg PBW (by 0.5ml/kg every 30 min) to reach ΔP 9-11 cm H2O and at least 5 cm H 2 O ΔP decrease * PEEP adjusted to keep the same mean airway pressure * Pump outflow set at 2-4 L/min , based on the need of blood oxygenation * RR decreased to a min of 12/min with gas flow rate adjusted to maintain PaCO2 45 mmHg. * Protocolized weaning of ECLS |
| Control : Conventional Treatment Arm | No intervention | –* Conventional management of ARDS * Ventilatory settings: * Volume assist control mode, * VT 6 ml/kg of predicted body weight * PEEP adjusted for Pplateau 28 29 cmH2O ; * FiO2 for 88%≤SaO2≤95% or 55 mmHg≤PaO2≤80 mm Hg * RR up to 35/mn, for a PaCO2 resulting in 7.30<pH<7.42 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Intubation and Invasive mechanical ventilation ≤ 7 days
- Presence of all of the following conditions for ≤48 hours:
- One of the following criteria (with Vt set at 6 mL/kg PBW):
- Signed Informed consent from a close relative or surrogate or a family member. According to the specifications of emergency inclusion, randomization without the close relative/surrogate consent could be performed if the patient is unable to give his/ger consent and when the close relative/surrogate/family member are absent. Close relative/surrogate/family member consent will be asked as soon as possible after randomization. The patient will be asked as soon as possible to give his/her consent for the continuation of the trial when his/her condition will allow.
- Social security registration (AME excluded)
Key exclusion criteria (15 listed)
- Age <18 years
- Pregnancy or breastfeeding
- Catheter access to femoral vein or jugular vein impossible
- Expected duration of mechanical ventilation < 48 hours
- Chronic restrictive or obstructive (COPD) respiratory insufficiency with home ventilation or oxygen therapy
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 |
|---|---|---|
| ECLS* ECLS catheters inserted, and EC LS initiated no later than 12h after randomization * Vt decreased to a min of 3 ml/kg PBW (by 0.5ml/kg every 30 min) to reach ΔP 9 -11 cmH2O and at least 5 cm H2O ΔP decrease * PEEP adjusted to keep the same mean airway pressure * Pump outflow set at 2-4 L/min , based on the need of blood oxygenation * RR decreased to a min of 12/min with gas flowrate adjusted to maintain PaCO2 45 mmHg. * Protocolized weaning of ECLS | Procedure or surgery | Expérimental : ECLS |
Primary outcome
Hierarchical criterion assessed at day 30, including all-cause mortality followed by the number of days free from MV at day 30, and calculated in such a manner that death constitutes a worse outcome than duration of ventilation.
Time frame: Day 30
Each patient is compared with every other patient in the study and assigned a score (tie: 0, win: +1, loss: -1) for each pairwise comparison based on whom fared better. - If one patient survived at day 30 and the other did not, scores of +1 and -1 will be assigned, respectively, for that pairwise comparison. If both patients in the pairwise comparison survived at day 30, the assigned score will depend on which patient had more days free from MV at day 30: the patient with more days off MV will receive a score of +1, while the patient with fewer days will receive a score of -1. If both patients survived and had the same number of days off MV, or if both patients died, they will be both assigned a score of 0 for that pairwise comparison. For each patient, scores for all pairwise comparisons will be summed, resulting in a cumulative score.
27 secondary outcomes
Mortality
Time frame: Day 30, Day 60, Day 90
Duration of mechanical ventilation
Time frame: From inclusion to Day 30, from inclusion to Day 60
Number of mechanical ventilation free days
Time frame: Day 30, Day 60
Duration of catecholamine hemodynamic support
Time frame: From inclusion to Day 30, from inclusion to Day 60
Number of catecholamine hemodynamic support free days
Time frame: Day 30, Day 60
Number of organ failure(s) free days
Time frame: Day 30, Day 60
Number of renal replacement therapy free days
Time frame: Day 30, Day 60
Durations of ICU stay
Time frame: Day 90
Duration of hospitalization
Time frame: Day 90
Proportion of patients with Pneumothorax
Time frame: Day 30, Day 60
Proportion of patient with rescue procedures and therapies for severe ARDS
Time frame: Day 90
Incidence of pump malfunction related to ECLS
Time frame: Day 90
Incidence of clotting related to ECLS
Time frame: Day 90
Incidence of air embolism related to ECLS
Time frame: Day 90
Incidence of hemolysis related to ECLS
Time frame: Day 90
Incidence of vein perforation related to ECLS
Time frame: Day 90
Incidence of significant bleeding (related to cannula insertion, at canula site) related to ECLS
Time frame: Day 90
Incidence of major hemorrhage related to ECLS
Time frame: Day 90
Incidence of infection at cannula site related to ECLS
Time frame: Day 90
Incidence of thromboembolic events related to ECLS
Time frame: Day 90
Incidence of stroke related to ECLS
Time frame: Day 90
Incidence of thrombocytopenia related to ECLS
Time frame: Day 90
Incidence of hypofibrinogenemia related to ECLS
Time frame: Day 90
Number of packed red blood cells transfused
Time frame: Day 90
Incidence of ventilator-associated pneumonia
Time frame: From inclusion to Day 30, form inclusion to Day 60
Number of days without organ failure(s), defined with the SOFA score
Time frame: Day 30, Day 60
Number of days without renal replacement therapy
Time frame: Day 30, Day 60
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 14 Apr 2026.
- Individual participant dataSharing planned: Yes. The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients. Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.
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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.
Questions about this trial
What is this clinical trial studying?
A study testing ECLS in people with Acute Respiratory Distress Syndrome (ARDS), run by Assistance Publique - Hôpitaux de Paris.
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 10 inclusion and 15 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: opening soon, as of the sponsor's last update on 14 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
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 Alain COMBES, Professor of medicine (+33142163818, alain.combes@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hierarchical criterion assessed at day 30, including all-cause mortality followed by the number of days free from MV at day 30, and calculated in such a manner that death constitutes a worse outcome than duration of ventilation. (time frame: Day 30). 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 14 Apr 2026.