Acute Respiratory Distress Syndrome ARDS Clinical Trial
— DRIVENTOfficial title:
Driving Pressure-guided Tidal Volume Ventilation in the Acute Respiratory Distress Syndrome: a Prospective, Multicenter, Randomized, Controlled, Open-label, Phase III Trial
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)
| Status | Not yet recruiting |
| Enrollment | 750 |
| Est. completion date | December 1, 2026 |
| Est. primary completion date | October 1, 2026 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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) |
| Country | Name | City | State |
|---|---|---|---|
| n/a | |||
| Lead Sponsor | Collaborator |
|---|---|
| Assistance Publique - Hôpitaux de Paris |
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Mortality | The primary endpoint is a ranked composite score that prioritizes 28-day mortality, followed by days free from mechanical ventilation through day 28 for the survivors. Thus, the score is calculated in such a manner that death constitutes a worse outcome than fewer days off the ventilator. | 28 days | |
| Primary | Number of days free from mechanical ventilation | The primary endpoint is a ranked composite score that prioritizes 28-day mortality, followed by days free from mechanical ventilation through day 28 for the survivors. Thus, the score is calculated in such a manner that death constitutes a worse outcome than fewer days off the ventilator. | 28 days | |
| Secondary | Ventilator parameters | up to Day 7 | ||
| Secondary | Arterial blood gases | Arterial blood gases (pH, PaO2, PaCO2, HCO3-), recorded in supine position between 6:00 and 12:00 a.m. once a day up to day 7 | up to Day 7 | |
| Secondary | Mortality | ICU mortality and hospital mortality | Day-28, Day 90 | |
| Secondary | Number of days alive without ventilation | Number of days alive without ventilation between randomization and day 28; | Up to Day 28 | |
| Secondary | Sequential Organ Failure Assessment score (SOFA) | SOFA score | Day 1, Day 3 and Day 7 | |
| Secondary | Number of days alive without catecholamine | Number of days alive without catecholamine between randomization and day 28, assessed as a hierarchical endpoint prioritized on 28-day mortality; | Up to Day 28 | |
| Secondary | Number of days alive without continuous sedation | Number of days alive without continuous sedation between randomization and day 28, assessed as a hierarchical endpoint prioritized on 28-day mortality | Up to Day 28 | |
| Secondary | Number of days alive without neuromuscular blockers | Number of days alive without neuromuscular blockers between randomization and day 28, assessed as a hierarchical endpoint prioritized on 28-day mortality; | UP to Day 28 | |
| Secondary | Number of prone position sessions | Number of prone position sessions | Up to Day 28 | |
| Secondary | Use of rescue procedures: inhaled nitric oxide, almitrine, ECMO, ECCO2R | Use of rescue procedures: inhaled nitric oxide, almitrine, ECMO, ECCO2R | Up to Day 28 | |
| Secondary | Occurrence of ventilator-associated pneumothorax | Occurrence of ventilator-associated pneumothorax between randomization and day 28; | Up to Day 28 | |
| Secondary | Time to pressure support ventilation; | Time between randomization and transition to pressure support ventilation; | Up to Day 28 | |
| Secondary | Duration of weaning unreadiness | Duration of weaning unreadiness measured as the time between randomization and initiation of weaning from mechanical ventilation, defined as the day of the first spontaneous breathing trial; | Up to Day 28 | |
| Secondary | Duration of weaning | Duration of weaning, defined as the time between the first spontaneous breathing trial and successful extubation | Up to day 28 | |
| Secondary | The rate of tracheostomy | The rate of tracheostomy | Up to Day 28 | |
| Secondary | Total duration of mechanical ventilation | Total duration of mechanical ventilation, from intubation to successful extubation, defined as an extubation not followed by reintubation or death within the next 7 days; | up to Day 7 | |
| Secondary | Length of stay | Length of stay in the ICU and in hospital; | up to Day 28 |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
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|
Phase 2/Phase 3 |