Protective Ventilatory Strategy in Severe Acute Brain Injury

NCT01690819 | Unknown DMC

• 1 other identifier: PROLABI
• Study Type: interventional
• Target: 524
• Locations: 1 country
• Sites: 1

Brief Summary

Acute respiratory distress syndrome (ARDS) occurs in almost 20% of patients with severe acute brain injury and is associated with increased morbidity and mortality. A massive increase in sympathetic activity and an increased production of proinflammatory cytokines released into the systemic circulation are the most important recognized mechanisms. Altered blood brain barrier after injury causes spillover of inflammatory mediators from the brain into the systemic circulation leading to peripheral organs damage. The adrenergic surge induces an increase in vascular hydrostatic pressure and lung capillary permeability, causing an alteration of alveolar capillary barrier with fluid accumulation, resulting in ARDS. The main goal of mechanical ventilation after acute brain injury are the maintenance of optimal oxygenation, and a tight control of carbon dioxide tension, although ventilatory settings to be used to obtain these targets, while avoiding secondary insults to the brain, are not clearly identified. Protective ventilatory strategy has been positively evaluated first in patients with ARDS, and then in those undergoing cardiopulmonary bypass or lung resection surgery, or in brain death organ donors, but data on the effect of protective mechanical ventilation on patients with acute brain injury are still lacking even if this is a population with recognized risk factors for ARDS. Therefore, the primary aim of this multi-center, prospective, randomized, controlled trial is to investigate whether a protective ventilatory strategy, in the early phase after severe acute brain injury, is associated with a lower incidence of ARDS, avoiding any further damage to the brain. Secondary aim is to evaluate if a protective ventilatory strategy is associated with reduced duration of mechanical ventilation, incidence of organ failure, intensive care unit length of stay, and lower concentrations of plasma inflammatory cytokines, without adversely affect in neurological outcome.

Conditions

Injuries, Acute Brain

Keywords

Acute Respiratory Distress Syndrome; Acute Brain Injury

Outcome Measures

Primary Outcomes (1)

• Proportion of event free survival

  Combined end point of "event free survival" defined as survival without ventilator dependency or ARDS\* diagnosis \*ARDS will be defined according to Berlin definition criteria. If chest x-ray is not immediately available, ARDS diagnosis will be suspected and confirmed later on. Interpretation of bilateral infiltrates on chest x-ray and of heart failure vs. fluid overload was variable and in a large observational study (LUNGSAFE, JAMA. 2016 Feb 23;315:788-800) hypoxemic patients with new infiltrates were described as a well-defined group with outcome, risk factors, comorbidities and clinical management similar to ARDS. Therefore, in March 2016 the study protocol replaced "ARDS" with "acute hypoxemic respiratory failure" as one of the components of the composite primary endpoint. Acute hypoxemic respiratory failure was defined as PaO2/FiO2 ratio \< 300, with presence of infiltrates on chest x-ray, independently of lung opacities distribution and characteristics.

  28 days

Secondary Outcomes (10)

• Number of ventilator free days at 28 days

  28 days

• number of ICU free days at day 28 after randomization

  participants will be followed for the duration of ICU stay, an expected average of 3 weeks

• Incidence of ventilator associated pneumonia (VAP)

  28 days

• Cumulative SOFA free score from the randomization to day 28

  28 days

• Concentrations of plasma inflammatory cytokines

  7 days

Study Arms (2)

Conventional Ventilatory Strategy

ACTIVE COMPARATOR

Conventional Ventilatory Strategy

Procedure: Conventional Ventilatory Strategy

Protective Ventilatory Strategy

EXPERIMENTAL

Protective ventilatory strategy

Procedure: Protective Ventilatory Strategy

Interventions

Conventional Ventilatory Strategy PROCEDURE

The conventional strategy will be the standard of care with a lower limit of tidal volume equal to 8 ml/Kg of predicted body weight and with a PEEP of 4 cmH2O

Conventional Ventilatory Strategy

Protective Ventilatory Strategy PROCEDURE

The protective strategy will consist of a tidal volume of 6 ml/Kg of predicted body weight, with a PEEP of 8 cmH2O

Protective Ventilatory Strategy

Eligibility Criteria

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

You may qualify if:

• Patients with severe acute brain injury (traumatic brain injury, subarachnoid haemorrhage, intra-cerebral haemorrhage, and ischemic stroke)
• Patients with not obey commands and do not open eyes on GCS (Glasgow Coma Scale)
• Less than 24 hours of mechanical ventilation (expected \>72 hours)

You may not qualify if:

• Age \< 18 years
• Diagnosis of ARDS before randomization.
• Patients unlikely to survive for the next 24 hours in the opinion of ICU consultant.
• Pregnancy
• Post-anoxic coma
• Metabolic or toxic encephalopathy
• Lack of Informed Consent.

Sponsors & Collaborators

• University of Turin, Italy: lead

Study Sites (1)

University of Turin - Department of Anesthesia and Intensive care Medicine

Turin, 10126, Italy

Location

Related Publications (1)

• Mascia L, Fanelli V, Mistretta A, Filippini M, Zanin M, Berardino M, Mazzeo AT, Caricato A, Antonelli M, Della Corte F, Grossi F, Munari M, Caravello M, Alessandri F, Cavalli I, Mezzapesa M, Silvestri L, Casartelli Liviero M, Zanatta P, Pelosi P, Citerio G, Filippini C, Rucci P, Rasulo FA, Tonetti T. Lung-Protective Mechanical Ventilation in Patients with Severe Acute Brain Injury: A Multicenter Randomized Clinical Trial (PROLABI). Am J Respir Crit Care Med. 2024 Nov 1;210(9):1123-1131. doi: 10.1164/rccm.202402-0375OC.

  PMID: 39288368 DERIVED

MeSH Terms

Conditions

Brain Injuries; Respiratory Distress Syndrome

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Study Officials

• Luciana Mascia, MD, PhD

  University of Turin, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: September 12, 2012
• First Posted: September 24, 2012
• Study Start: October 1, 2013
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2021
• Last Updated: April 26, 2021

Record last verified: 2021-04

Locations

IT (1)