Brain Recovery With Automated VEntilation (BRAVE)

Effectiveness, Safety and Efficacy of Closed-Loop Ventilation in Acute Brain Injury-Patients

Thus far, the closed-loop ventilation mode INTELLiVENT-ASV has been extensively tested in various groups of critically ill patients, and has been shown to be effective and safe in various groups of ventilated patients, including those at risk of acute respiratory distress syndrome (ARDS), patients with ARDS, and patients with chronic obstructive pulmonary disease (COPD). Some of these studies included acute brain injury (ABI) patients, but the effectiveness, efficacy and safety of INTELLiVENT-ASV has never been thoroughly tested in these patients. The current study will investigate the effectiveness in providing both brain- and lung protective ventilation, the safety and the efficacy of a closed-loop ventilation mode (INTELLiVENT-ASV) in acute brain injury patients, using breath-by-breath data.

Study Overview

• Status: Completed
• Conditions: Respiration, Artificial; Automation; Brain Injuries, Acute
• Intervention / Treatment: Procedure: INTELLiVENT; Procedure: Conventional ventilation

Detailed Description

Rationale: Closed-loop ventilation has been proven effective in lung-protective ventilation but its effectiveness, safety and efficacy in providing both lung- and brain-protective ventilation in patients with acute brain injury has not been investigated.

Objective: To evaluate the effectiveness, efficacy and safety of INTELLiVENT-ASV with respect to brain- and lung-protective ventilation in ABI patients

Hypothesis: We hypothesize that INTELLiVENT-ASV is effective with regard to brain- and lung-protective ventilation (that is achieving brain- and lung- protective targets), efficacious (that is improving outcomes), and that INTELLiVENT-ASV is safe in invasively ventilated ABI patients.

Study design: Single-center, crossover trial.

Methods: In this prospective observational study, breath-by-breath ventilation data will be available from before and after the switch to closed-loop ventilation with INTELLiVENT-ASV, wherein the decision to switch is determined by the attending healthcare worker, i.e., not protocolized and only for clinical/organizational reasons. High granular data are collected both before and after this switch, limited to three hours for conventional and three hours for closed-loop ventilation. Neuromonitoring is part of current clinical practice and data will be collected only when available.

Study population: Invasively ventilated patients diagnosed with acute brain injury Methods: When the ventilator is switched upon the caregivers decision, data will be collected from three hours before the switch and three hours after the switch.

Study endpoints: The primary composite endpoint is the proportion of breaths and proportion of time within predefined zones of ventilation (based on VT and airway pressures, saturation of peripheral O2 (SpO2) and end-tidal CO2 (EtCO2).

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• Italy
  • GE
    • Genova, GE, Italy, 16132
      • UO Clinica Anestesiologica e Terapia Intensiva, IRCCS Ospedale Policlinico San Martino

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Invasively ventilated acute brain injury (ABI) patients admitted to the ICU of the Policlinico San Martino Hospital, Genova, Italy

Description

Inclusion Criteria:

• aged ≥ 18 years;
• intubated and receiving invasive ventilation for ABI;
• admitted to the Intensive Care Unit

Exclusion Criteria:

- receiving ventilation with a ventilator that does not allow INTELLiVENT-ASV

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of breaths in predefined zones of ventilation	7 hours from baseline
Proportion of time in predefined zones of ventilation	7 hours from baseline

Secondary Outcome Measures

Outcome Measure	Time Frame
Hospital length of stay	90 days
90-day mortality	90 days
Intracerebral changes assessed by multimodal neuromonitoring available	7 hours from baseline
Changes on Electrical Impedence Tomography when available	7 hours from baseline
Effectiveness in primary ABI patients vs non primary ABI patients	7 hours from baseline
Episodes and time of high maximum airway pressure	7 hours from baseline
Episodes and time of high respiratory rate	7 hours from baseline
Incidence of severe hypoxemia	7 hours from baseline
Incidence of severe hypercapnia	7 hours from baseline
Discontinuation of ventilatory mode (yes or no)	7 hours from baseline
Percentage of breaths in the predefined 'critical' ventilation zone	7 hours from baseline
Incidence of pneumothorax	8 hours from baseline
Efficacy on glascow coma scale	7 hours from baseline
Duration of ventilation in survivors	90 days
Ventilator free days	90 days
Intensive care unit length of stay	90 days
28-day mortality	90 days
Number of alarms	7 hours from baseline
Number of manual adjustments	7 hours from baseline

Collaborators and Investigators

• Sponsor: University of Genova

Publications and helpful links

General Publications

• Goossen RL, Gavinelli S, Dragoni S, van Meenen DMP, Paulus F, Schultz MJ, Ball L, Patroniti NA, Robba C. Brain protective ventilation in acute brain injury patients with use of fully automated ventilation (BRAVE): A cross-over clinical trial. Eur J Anaesthesiol. 2026 Mar 1;43(3):235-244. doi: 10.1097/EJA.0000000000002253. Epub 2025 Aug 22.

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2024
• Primary Completion (Actual): October 31, 2024
• Study Completion (Actual): December 31, 2024

Study Registration Dates

• First Submitted: April 11, 2024
• First Submitted That Met QC Criteria: April 11, 2024
• First Posted (Actual): April 16, 2024

Study Record Updates

• Last Update Posted (Actual): March 10, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Craniocerebral Trauma; Trauma, Nervous System; Pathological Conditions, Signs and Symptoms; Respiratory Aspiration; Brain Injuries
• Other Study ID Numbers: 13509

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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