Lung and Diaphragm-Protective Ventilation by Means of Assessing Respiratory Work (LANDMARK)

This study is designed to test a proposed strategy for lung- and diaphragm-protective ventilation (LDPV) in patients with acute hypoxemic respiratory failure. Ventilation and sedation will be titrated to evaluate whether it is feasible and safe within this patient population.

Study Overview

• Status: Completed
• Conditions: Respiratory Insufficiency; Lung Injury; Mechanical Ventilation Complication; Diaphragm Injury
• Intervention / Treatment: Procedure: Lung- and Diaphragm-Protective Ventilation

Detailed Description

Lung injury and diaphragm injury incurred by mechanical ventilation have very serious adverse effects on patients with acute respiratory failure. Lung injury results from excessive mechanical stress and strain applied to the lung by the ventilator and/or respiratory muscles, while diaphragm injury results from either insufficient or excessive inspiratory effort.

The objective of this study is to investigate a new LDPV strategy designed to prevent both disuse-mediated and load-induced diaphragm injury, while also preventing excess global and regional mechanical stress and strain in the injured lung. To achieve these goals, the following specific targets to be met are: (1) respiratory muscle effort similar to that of healthy subjects breathing at rest, (2) lung stress within safe limits, and (3) clinically acceptable gas exchange.

Targets are assessed through measurements of global lung stress, tidal recruitment, inspiratory effort, diaphragm contractile effort and adequacy of respiratory muscle and systemic tissue perfusion. Measurements commence at enrollment and continue for 24 hours consecutively.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • University Health Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosed with acute hypoxemic respiratory failure
• PaO2:FiO2 ratio less than or equal to 300 mm Hg at time of screening
• Oral endotracheal intubation and mechanical ventilation
• Bilateral airspace opacities on chest radiograph or chest CT scan

Exclusion Criteria:

• Liberation from mechanical ventilation is anticipated within 24 hours
• Intubated for traumatic brain injury or stroke
• Contraindication to esophageal catheterization
• Intracranial hypertension

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lower PEEP; Lung- and Diaphragm-Protective Ventilation - PEEP will be set at 8 cm H2O	Procedure: Lung- and Diaphragm-Protective Ventilation; Ventilation and sedation will be progressively modified according to the LDPV algorithm to achieve targets. Patients will be crossed-over to the opposite PEEP strategy. LDPV titration will then be repeated to achieve LDPV targets. After establishing a combination of ventilation and sedation settings at which LDPV targets are achieved, the targets will be maintained over a 24-hour period.; Other Names: LDPV
Experimental: Higher PEEP; Lung- and Diaphragm-Protective Ventilation - PEEP will be titrated to achieve end-expiratory PL = 2-3 cm H20 and at least 5 cm H2O greater than the level applied in the lower PEEP arm	Procedure: Lung- and Diaphragm-Protective Ventilation; Ventilation and sedation will be progressively modified according to the LDPV algorithm to achieve targets. Patients will be crossed-over to the opposite PEEP strategy. LDPV titration will then be repeated to achieve LDPV targets. After establishing a combination of ventilation and sedation settings at which LDPV targets are achieved, the targets will be maintained over a 24-hour period.; Other Names: LDPV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of patients achieving and maintaining LDPV targets	Assessed after achievement of LDPV targets for 24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inspiratory effort at lower and higher PEEP levels		Assessed 10 minutes after PEEP and sedation are adjusted
Expiratory diaphragmatic effort at lower and higher PEEP levels		Assessed 10 minutes after PEEP and sedation are adjusted
Lung stress and strain at low and high sweep gas flow rates		Assessed 10 minutes after PEEP and sedation are adjusted
Inspiratory effort at low and high sweep gas flow rates		Assessed 10 minutes after PEEP and sedation are adjusted
Sedative infusion rate at low and high sweep gas flow rates		Assessed 10 minutes after PEEP and sedation are adjusted
Accuracy of artificial intelligence model in predicting patient outcomes	We will compare the model's prediction of patient's esophageal pressure, pH and transpulmonary pressure to the actual observed values	Assessed after completing the 24-hour maintenance period

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Ewan Goligher, MD, PhD, University Health Network, Toronto

Publications and helpful links

General Publications

• Dianti J, Fard S, Wong J, Chan TCY, Del Sorbo L, Fan E, Amato MBP, Granton J, Burry L, Reid WD, Zhang B, Ratano D, Keshavjee S, Slutsky AS, Brochard LJ, Ferguson ND, Goligher EC. Strategies for lung- and diaphragm-protective ventilation in acute hypoxemic respiratory failure: a physiological trial. Crit Care. 2022 Aug 29;26(1):259. doi: 10.1186/s13054-022-04123-9.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2019
• Primary Completion (Actual): November 30, 2022
• Study Completion (Actual): November 30, 2022

Study Registration Dates

• First Submitted: July 5, 2018
• First Submitted That Met QC Criteria: August 1, 2018
• First Posted (Actual): August 2, 2018

Study Record Updates

• Last Update Posted (Actual): December 10, 2024
• Last Update Submitted That Met QC Criteria: December 6, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Sedation; Mechanical Ventilation; Acute Respiratory Failure; Diaphragm Dysfunction; Lung Stress
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Thoracic Injuries; Respiratory Insufficiency; Wounds and Injuries; Lung Injury
• Other Study ID Numbers: 18-5644

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
• product manufactured in and exported from the U.S.: No