Effectiveness of Low Volume and Low Pressure in Severe Hypoxemic Patients (avengARDS)

Assessing the Effectiveness of Low Tidal Volume and Low Driving Pressure in Mechanically Ventilated Severe Hypoxemic Patients: a Multicenter Emulated Target Trial

The present study set up to answer two questions: (a) "how low tidal volume must be to provide protective ventilatory settings able to minimize the risk of death due to Ventilator-Induced Lung Injury (VILI)?"; (b) "if protection from VILI is better achieved by targeting the driving pressure instead of the tidal volume, what is the optimal target for the driving pressure?". Solving these questions is pivotal for clinicians to personalized and precise mechanical ventilation practices to reduce the risk of VILI and avoid unnecessary risks associated to protective ventilatory settings.

Two multicenter emulated target trials will be performed using data collected with the Electronic Health Record MargheritaTre, to investigate the effect of low tidal volumes (6.0 to 8.0 ml/kg PBW vs 8.0 to 10.0 ml/kg PBW) and low driving pressures (7.0-12.0 cmH2O vs 12.0-18.0 cmH2O), respectively. Data will be used to obtain the dose-response curve of lower VT and lower ∆P in mechanically ventilated patients with acute severe hypoxemia.

Study Overview

• Status: Active, not recruiting
• Conditions: Hypoxemia; Ards
• Intervention / Treatment: Device: low tidal volume; Device: high tidal volume; Device: low driving pressure; Device: high driving pressure

• Study Type: Observational
• Enrollment (Estimated): 4300

Contacts and Locations

Study Locations

• Italy
  • BG
    • Ranica, BG, Italy, 24020
      • Mario Negri Institute for Pharmacological Research IRCCS

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

All adult patients admitted to an ICU adopting MargheritaTre as electronic health record satisfying inclusion and exclusion criteria.

Description

Inclusion Criteria:

all the following conditions present continuously for 24 hours commencing within 36 hours of ICU admission, while the patient is undergoing invasive mechanical ventilation in either flow or pressure- regulated assist/controlled modes:

1. arterial oxygen tension (PaO2) to inspiratory oxygen fraction (FiO2) ratio P/F ≤ 300 mmHg
2. hypoxemia developed within one week of a known clinical insult
3. hypoxemia not fully explained by cardiac failure or fluid overload*

Exclusion Criteria:

1. pregnancy
2. expected duration of mechanical ventilation < 48h
3. severe or moderate COPD
4. chronic liver disease
5. acute brain injury
6. patient admitted for palliative sedation
7. tumor with metastases
8. prior cardiac arrest
9. New York Heart Association Class IV
10. acute coronary syndrome
11. patients transferred from other ICUs
12. patients transferred to the ICU from the Emergency Department after a duration exceeding 24 hours in the Emergency Department
13. patients on Pressure Support Ventilation and/or patients in whom end-inspiratory plateau pressure was not measured

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
VT1 - low tidal volume; Patients mechanically ventilated with tidal volume between 6.0 and 8.0 ml/kg PBW, until weaning conditions are satisfied. When weaning criteria are met, extubation may be attempted, it may either fail or not, or any other mechanical ventilation regime may be chosen, according to clinical practice.	Device: low tidal volume; Patients ventilated with assist/control modes of mechanical ventilation with tidal volume between 6.0 ml/kg PBW and 8.0 ml/kg PBW with PPLAT ≤ 30 cmH2O, until weaning criteria are met: P/F ratio > 250 mmHg; PEEP ≤ 8 cmH2O and lower than the previous day; FiO2 < 0.5 and lower than the previous day; systolic arterial pressure ≥ 85 mmHg.
VT2 - high tidal volume; Patients mechanically ventilated with tidal volume between 8.0 and 10.0 ml/kg PBW, until weaning conditions are satisfied. When weaning criteria are met, extubation may be attempted, it may either fail or not, or any other mechanical ventilation regime may be chosen, according to clinical practice.	Device: high tidal volume; Patients ventilated with assist/control modes of mechanical ventilation with tidal volume between 8.0 ml/Kg PBW and 10.0 ml/kg PBW with PPLAT ≤ 30 cmH2O, until weaning criteria are met: P/F ratio > 250 mmHg; PEEP ≤ 8 cmH2O and lower than the previous day; FiO2 < 0.5 and lower than the previous day; systolic arterial pressure ≥ 85 mmHg.
∆P1 - low driving pressure; Patients mechanically ventilated with driving pressure between 7.0 and 12.0 cmH2O, until weaning conditions are satisfied. When weaning criteria are met, extubation may be attempted, it may either fail or not, or any other mechanical ventilation regime may be chosen, according to clinical practice.	Device: low driving pressure; Patients ventilated with assist/control modes of mechanical ventilation with driving pressure between 7.0 cmH2O and 12.0 cmH2O with VT ≤ 10 ml/kg PBW, until weaning criteria are met: P/F ratio > 250 mmHg; PEEP ≤ 8 cmH2O and lower than the previous day; FiO2 < 0.5 and lower than the previous day; systolic arterial pressure ≥ 85 mmHg.
∆P2 - high driving pressure; Patients mechanically ventilated with driving pressure between 12.0 and 18.0 cmH2O, until weaning conditions are satisfied. When weaning criteria are met, extubation may be attempted, it may either fail or not, or any other mechanical ventilation regime may be chosen, according to clinical practice.	Device: high driving pressure; Patients ventilated with assist/control modes of mechanical ventilation with driving pressure between 12.0 cmH2O and 18.0 cmH2O with VT ≤ 10 ml/kg PBW, until weaning criteria are met: P/F ratio > 250 mmHg; PEEP ≤ 8 cmH2O and lower than the previous day; FiO2 < 0.5 and lower than the previous day; systolic arterial pressure ≥ 85 mmHg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU all-cause mortality	All patients will be classified as either alive if "alive at ICU discharge" or dead if "dead at ICU discharge"	14 days from assignment to intervention arm

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilator-free days	Number of ventilator-free days (VFDs) during the 14 days in ICU	14 days from assignment to intervention arm

Collaborators and Investigators

• Sponsor: Gruppo Italiano per la Valutazione degli Interventi in Terapia Intensiva
• Collaborators: University of Bari Aldo Moro; Istituto di Ricerche Farmacologiche Mario Negri IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): December 24, 2024
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: July 16, 2024
• First Submitted That Met QC Criteria: July 16, 2024
• First Posted (Actual): July 22, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 23, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Respiratory; Hypoxia
• Other Study ID Numbers: avengARDS

Drug and device information, study documents

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