Effectiveness of Low Volume and Low Pressure in Severe Hypoxemic Patients

Active, not recruiting

• Conditions: Hypoxemia; Ards
• Interventions: Device: low driving pressure; Device: low tidal volume; Device: high tidal volume; Device: high driving pressure

• Registration Number: NCT06513299
• Lead Sponsor: Gruppo Italiano per la Valutazione degli Interventi in Terapia Intensiva

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-07-16
• Study First Submitted QC: 2024-07-16
• Study First Posted: 2024-07-22
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-23
• Study Start: 2024-12-24
• Last Update Posted: 2024-12-27
• Primary Completion: 2025-08-01
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 4300

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
∆P1 - low driving pressure	low driving pressure	Patients mechanically ventilated with driving pressure between 10.0 and 15.0 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.
VT1 - low tidal volume	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.
VT2 - high tidal volume	high tidal volume	Patients mechanically ventilated with tidal volume between 8.1 and 11.9 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.
∆P2 - high driving pressure	high driving pressure	Patients mechanically ventilated with driving pressure between 15.1 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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Ventilator-free days	14 days from assignment to intervention arm	Number of ventilator-free days (VFDs) during the 14 days in ICU

Trial Locations

Locations (1)

Mario Negri Institute for Pharmacological Research IRCCS; 🇮🇹 Ranica, BG, Italy