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NCT Number: NCT07516665

Ultraprotective Lung Ventilation With Respiratory Extracorporeal Life Support for ARDS

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.

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Key information

Conditions

Acute Respiratory Distress Syndrome (ARDS) Lung Diseases Respiration Disorders Respiratory Distress Syndrome Respiratory Tract Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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):
  • 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)

Exclusion criteria

  • 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
  • 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

Treatment and study plan

ECLS

Procedure
  • 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

Primary outcomes

  1. 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.

Secondary outcomes

  1. Mortality

    Time frame: Day 30, Day 60, Day 90

  2. Duration of mechanical ventilation

    Time frame: From inclusion to Day 30, from inclusion to Day 60

  3. Number of mechanical ventilation free days

    Time frame: Day 30, Day 60

  4. Duration of catecholamine hemodynamic support

    Time frame: From inclusion to Day 30, from inclusion to Day 60

  5. Number of catecholamine hemodynamic support free days

    Time frame: Day 30, Day 60

  6. Number of organ failure(s) free days

    Time frame: Day 30, Day 60

  7. Number of renal replacement therapy free days

    Time frame: Day 30, Day 60

  8. Durations of ICU stay

    Time frame: Day 90

  9. Duration of hospitalization

    Time frame: Day 90

  10. Proportion of patients with Pneumothorax

    Time frame: Day 30, Day 60

  11. Proportion of patient with rescue procedures and therapies for severe ARDS

    Time frame: Day 90

  12. Incidence of pump malfunction related to ECLS

    Time frame: Day 90

  13. Incidence of clotting related to ECLS

    Time frame: Day 90

  14. Incidence of air embolism related to ECLS

    Time frame: Day 90

  15. Incidence of hemolysis related to ECLS

    Time frame: Day 90

  16. Incidence of vein perforation related to ECLS

    Time frame: Day 90

  17. Incidence of significant bleeding (related to cannula insertion, at canula site) related to ECLS

    Time frame: Day 90

  18. Incidence of major hemorrhage related to ECLS

    Time frame: Day 90

  19. Incidence of infection at cannula site related to ECLS

    Time frame: Day 90

  20. Incidence of thromboembolic events related to ECLS

    Time frame: Day 90

  21. Incidence of stroke related to ECLS

    Time frame: Day 90

  22. Incidence of thrombocytopenia related to ECLS

    Time frame: Day 90

  23. Incidence of hypofibrinogenemia related to ECLS

    Time frame: Day 90

  24. Number of packed red blood cells transfused

    Time frame: Day 90

  25. Incidence of ventilator-associated pneumonia

    Time frame: From inclusion to Day 30, form inclusion to Day 60

  26. Number of days without organ failure(s), defined with the SOFA score

    Time frame: Day 30, Day 60

  27. Number of days without renal replacement therapy

    Time frame: Day 30, Day 60

Study contacts

Contact information is provided by the study sponsor or research team.

Alain COMBES, Professor of medicine

CONTACT

[email protected]

+33142163818

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Acronym: NOVAEOLIA

Important dates

Study start
2026
Primary completion
2028
Study completion
2028
First posted
Apr 8, 2026
Registry last updated
Apr 14, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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