Effectiveness of Low Volume and Low Pressure in Severe Hypoxemic Patients

NCT06513299 | Active Not Recruiting

• 1 other identifier: avengARDS
• Study Type: observational
• Target: 4,300
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hypoxemia; Ards

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Ventilator-free days

  14 days from assignment to intervention arm

Study Arms (4)

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

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

∆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

∆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

Interventions

low tidal volume DEVICE

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.

VT1 - low tidal volume

high tidal volume DEVICE

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.

VT2 - high tidal volume

low driving pressure DEVICE

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.

∆P1 - low driving pressure

high driving pressure DEVICE

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.

∆P2 - high driving pressure

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Gruppo Italiano per la Valutazione degli Interventi in Terapia Intensiva: lead
• Istituto Di Ricerche Farmacologiche Mario Negri: collaborator
• University of Bari Aldo Moro: collaborator

Study Sites (1)

Mario Negri Institute for Pharmacological Research IRCCS

Ranica, BG, 24020, Italy

Location

MeSH Terms

Conditions

Hypoxia; Acute Lung Injury

Condition Hierarchy (Ancestors)

Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Lung Injury; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2024
• First Posted: July 22, 2024
• Study Start: December 24, 2024
• Primary Completion: August 1, 2025
• Study Completion: December 31, 2025
• Last Updated: December 27, 2024

Record last verified: 2024-12

Locations

IT (1)