Clinical trial NCT06322758: Driving Pressure-guided Tidal Volume Ventilation in the Acute Respiratory Distress Syndrome
Official title: Driving Pressure-guided Tidal Volume Ventilation in the Acute Respiratory Distress Syndrome: a Prospective, Multicenter, Randomized, Controlled, Open-label, Phase III Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Acute Respiratory Distress Syndrome ARDS
Keywords: Acute respiratory distress syndrome (ARDS)
ventilator-induced lung injury (VILI)
respiratory system compliance (Crs)
tidal volume (VT)
driving pressure (ΔP)
predicted body weight (PBW)
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2024-03-21
Enrollment: 750
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: comparing ΔP-guided VT to traditional PBW-guided VT during mechanical ventilation of patients with ARDS.
Primary purpose: TREATMENT

Brief summary: Acute respiratory distress syndrome (ARDS) is associated with high mortality, some of which can be attributed to ventilator-induced lung injury (VILI) when artificial ventilation is not customized to the severity of lung injury. As ARDS is characterized by a decrease in aerated lung volume, reducing tidal volume (VT) from 12 to 6 mL/kg of predicted body weight (PBW) was shown to improve survival more than 20 years ago. Since then, the VT has been normalized to the PBW, meaning to the theoretical lung size (before the disease), rather than tailored to the severity of lung injury, i.e., to the size of aerated lung volume. During ARDS, the aerated lung volume is correlated to the respiratory system compliance (Crs). The driving pressure (ΔP), defined as the difference between the plateau pressure and the positive end expiratory pressure, represents the ratio between the VT and the Crs. Therefore, the ΔP normalizes the VT to a surrogate of the aerated lung available for ventilation of the diseased lung, rather than to the theoretical lung size of the healthy lung, and thus represents more accurately the actual strain applied to the lungs. In a post hoc analysis of 9 randomized controlled trials, Amato et al. found that higher ΔP was a better predictor of mortality than higher VT, with an increased risk of death when the ΔP \> 14 cm H2O. These findings have been confirmed in subsequent meta-analysis and large-scale observational data. In a prospective study including 50 patients, the investigators showed that a ΔPguided ventilation strategy targeting a ΔP between 12 and 14 cm H2O significantly reduced the mechanical power, a surrogate for the risk of VILI, compared to a conventional PBW-guided ventilation. In the present study, the investigators hypothesize that the physiological individualization of ventilation (ΔP-guided VT) may improve the outcome of patients with ARDS compared to traditional anthropometrical adjustment (PBW-guided VT)


Eligibility criteria: Inclusion Criteria:

* Age \> 18 years
* Invasive mechanical ventilation
* Criteria for ARDS according to Berlin definition:
* Bilateral infiltrates not fully explained by effusions, lobar/lung collapse, or nodules;
* PaO2/FiO2 of 300 or less measured with a PEEP of at least 5 cm H2O
* Respiratory failure not fully explained by cardiac failure or fluid overload These criteria must be observed for less than 72h
* Affiliation to the social security system
* Written consent obtained from the patients (from a support person, family member or a close relative if the patient is not able to expressing and sign consent) or inclusion without initial consent in case of emergency, if the patient is not able to express his/her consent and in the absence of support person, family member or a close relative

Exclusion Criteria:

* Known pregnancy
* Lung transplantation
* Evident significant decrease in chest wall compliance (e.g., abdominal compartment syndrome)
* Moribund patient not expected to survive 24 hours
* Presence of an advanced directive to withhold life-sustaining treatment or decision to withhold life-sustaining treatment
* Chronic respiratory disease requiring home oxygen therapy or ventilation
* ECMO before inclusion
* Pneumothorax
* Enrollment in an interventional ARDS trial with direct impact on VT
* Subject deprived of freedom, subject under a legal protective measure (guardianship/curatorship)

Primary outcomes:
measure: Mortality
timeFrame: 28 days
measure: Number of days free from mechanical ventilation
timeFrame: 28 days
Secondary outcomes:
measure: Ventilator parameters
timeFrame: up to Day 7
measure: Arterial blood gases
timeFrame: up to Day 7
measure: Mortality
timeFrame: Day-28, Day 90
measure: Number of days alive without ventilation
timeFrame: Up to Day 28
measure: Sequential Organ Failure Assessment score (SOFA)
timeFrame: Day 1, Day 3 and Day 7
measure: Number of days alive without catecholamine
timeFrame: Up to Day 28
measure: Number of days alive without continuous sedation
timeFrame: Up to Day 28
measure: Number of days alive without neuromuscular blockers
timeFrame: UP to Day 28
measure: Number of prone position sessions
timeFrame: Up to Day 28
measure: Use of rescue procedures: inhaled nitric oxide, almitrine, ECMO, ECCO2R
timeFrame: Up to Day 28
measure: Occurrence of ventilator-associated pneumothorax
timeFrame: Up to Day 28
measure: Time to pressure support ventilation;
timeFrame: Up to Day 28
measure: Duration of weaning unreadiness
timeFrame: Up to Day 28
measure: Duration of weaning
timeFrame: Up to day 28
measure: The rate of tracheostomy
timeFrame: Up to Day 28
measure: Total duration of mechanical ventilation
timeFrame: up to Day 7
measure: Length of stay
timeFrame: up to Day 28
Other outcomes:
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