Driving Pressure-guided Tidal Volume Ventilation in the Acute Respiratory Distress Syndrome (DRIVENT)

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)

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Respiratory Distress Syndrome ARDS
• Intervention / Treatment: Other: Tidal volume customization in the acute respiratory distress syndrome

• Study Type: Interventional
• Enrollment (Estimated): 750
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Guillaume CARTEAUX, Pr; Phone Number: +33 (0)1 49 81 43 85; Email: guillaume.carteaux@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ΔP-guided VT group; During volume assist control ventilation, the VT will be adjusted in supine position to target a 12 ≤ ΔP ≤ 14 cm H2O. The allowed minimal and maximal values of VT are consistent with usual practices reported in large observational studies 4 and 10 mL/kg of PBW, respectively, while keeping a plateau pressure below 30 cm H2O. The respiratory rate will then be adjusted to meet the pH target	Other: Tidal volume customization in the acute respiratory distress syndrome; During volume assist control ventilation, the VT will be adjusted in supine position to target a 12 ≤ ΔP ≤ 14 cm H2O. The allowed minimal and maximal values of VT are consistent with usual practices reported in large observational studies 4 and 10 mL/kg of PBW, respectively, while keeping a plateau pressure below 30 cm H2O. The respiratory rate will then be adjusted to meet the pH target
Active Comparator: PBW-guided VT group; The VT will be kept at 6 mL/kg of PBW. If the plateau pressure threshold is reached (30 cm H2O), the VT will be decreased down to a minimal value of 4 mL/kg of PBW.	Other: Tidal volume customization in the acute respiratory distress syndrome; During volume assist control ventilation, the VT will be adjusted in supine position to target a 12 ≤ ΔP ≤ 14 cm H2O. The allowed minimal and maximal values of VT are consistent with usual practices reported in large observational studies 4 and 10 mL/kg of PBW, respectively, while keeping a plateau pressure below 30 cm H2O. The respiratory rate will then be adjusted to meet the pH target

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Number of days alive without ventilation	Number of days alive without ventilation between randomization and day 28;	Up to Day 28
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
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
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
Number of prone position sessions	Number of prone position sessions	Up to Day 28
Use of rescue procedures: inhaled nitric oxide, almitrine, ECMO, ECCO2R	Use of rescue procedures: inhaled nitric oxide, almitrine, ECMO, ECCO2R	Up to Day 28
Occurrence of ventilator-associated pneumothorax	Occurrence of ventilator-associated pneumothorax between randomization and day 28;	Up to Day 28
Time to pressure support ventilation;	Time between randomization and transition to pressure support ventilation;	Up to Day 28
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
Duration of weaning	Duration of weaning, defined as the time between the first spontaneous breathing trial and successful extubation	Up to day 28
The rate of tracheostomy	The rate of tracheostomy	Up to Day 28
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
Length of stay	Length of stay in the ICU and in hospital;	up to Day 28
Ventilator parameters		up to Day 7
Mortality	ICU mortality and hospital mortality	Day-28, Day 90
Sequential Organ Failure Assessment score (SOFA)	SOFA score	Day 1, Day 3 and Day 7

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: March 14, 2024
• First Submitted That Met QC Criteria: March 14, 2024
• First Posted (Actual): March 21, 2024

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: November 1, 2023

More Information

Terms related to this study

• 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)
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: APHP230851

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: DATAS ARE OWN BY ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS, PLEASE CONTACT SPONSOR FOR FURTHER INFORMATION

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No