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

NCT06322758 | Not Yet Recruiting

• 1 other identifier: APHP230851
• Study Type: interventional
• Target: 750
• Locations: 0 countries
• Sites: N/A

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)

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)

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (17)

• Ventilator parameters

  up to Day 7

• Arterial blood gases

  up to Day 7

• Mortality

  Day-28, Day 90

• Number of days alive without ventilation

  Up to Day 28

• Sequential Organ Failure Assessment score (SOFA)

  Day 1, Day 3 and Day 7

Study Arms (2)

ΔP-guided VT group

EXPERIMENTAL

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

PBW-guided VT group

ACTIVE COMPARATOR

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

Interventions

Tidal volume customization in the acute respiratory distress syndrome OTHER

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

PBW-guided VT group; ΔP-guided VT group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Pneumothorax
• Enrollment in an interventional ARDS trial with direct impact on VT
• Subject deprived of freedom, subject under a legal protective measure (guardianship/curatorship)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

MeSH Terms

Conditions

Respiratory Distress Syndrome; Ventilator-Induced Lung Injury; Acrocephalosyndactylia

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Lung Injury; Craniosynostoses; Synostosis; Dysostoses; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Syndactyly; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Limb Deformities, Congenital; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

Guillaume CARTEAUX, Pr

CONTACT

+33 (0)1 49 81 43 85; guillaume.carteaux@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: comparing ΔP-guided VT to traditional PBW-guided VT during mechanical ventilation of patients with ARDS.

Study Record Dates

• First Submitted: March 14, 2024
• First Posted: March 21, 2024
• Study Start: September 1, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 26, 2024

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share