Ventilation Strategy for Acute Respiratory Distress Syndrome

(CAVIARDS Trial)

Recruiting at31 trial locations

Overseen by Laurent Brochard, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Unity Health Toronto

Disqualifiers: Pregnancy, Severe liver disease, ECMO, others

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial tests if adjusting ventilator settings based on lung measurements can reduce deaths in ARDS patients, including those with COVID-19. The goal is to provide better breathing support without causing more lung damage.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment strategy for acute respiratory distress syndrome?

Research shows that using a ventilatory strategy with low tidal volumes (smaller breaths) and positive end expiratory pressure (keeping some air in the lungs at the end of a breath) can reduce lung injury and improve outcomes in patients with acute respiratory distress syndrome. ^{1 2 3 4 5}

How is the treatment 'Respiratory Mechanics' unique for acute respiratory distress syndrome?

The treatment 'Respiratory Mechanics' for acute respiratory distress syndrome is unique because it focuses on using mechanical ventilation strategies that limit lung overdistention by employing small tidal volumes and adjusting pressures to prevent lung injury. This approach aims to protect the lungs by allowing them to rest and avoid damage from high pressures, which is different from other treatments that might not emphasize these protective strategies. ^{6 7 8 9 10}

Research Team

Laurent Brochard, MD

Principal Investigator

Unity Health Toronto

Eligibility Criteria

This trial is for adults over 18 with moderate or severe ARDS, a type of lung failure, diagnosed within the past 48 hours. It's not for those with severe liver disease, on ECMO at randomization time, ventilated >7 days already, pregnant women, suspected high brain pressure needing PaCO2 control, broncho-pleural fistula cases, BMI >40kg/m2 or if life support withdrawal is anticipated.

Inclusion Criteria

I am 18 years old or older.

I have severe breathing problems and was diagnosed with ARDS recently.

Exclusion Criteria

I need specific treatment to manage high pressure in my brain.

Known pregnancy

I have a connection between my lung and chest wall.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mechanical ventilation based on respiratory mechanics to reduce Day 60 mortality in ARDS patients

Up to 60 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including mortality at ICU discharge, 28 days, and hospital discharge

Up to 60 days

Long-term follow-up

Participants are monitored for long-term outcomes such as organ dysfunction and biomarker changes

May exceed 60 days

Treatment Details

Interventions

• Respiratory Mechanics (Respiratory Mechanics)
• Standard Ventilation Strategy (Procedure)

Trial Overview The CAVIARDS study tests whether setting ventilators based on respiratory mechanics can lower the chance of dying by day 60 in ARDS patients. This includes both COVID-19 and non-COVID-19 patients in an adaptive randomized controlled trial comparing standard ventilation strategies to this new approach.

Participant Groups

Group I: Respiratory Mechanics Experimental Treatment 1 Intervention

The goal of this arm is to individualize tidal volume (VT) and PEEP according to respiratory mechanics.

Group II: Control Active Control 1 Intervention

Standard ventilation strategy.

Who Is Running the Clinical Trial?

Unity Health Toronto

Lead Sponsor

Trials

572

Recruited

470,000+

Dr. Sharon Straus

Unity Health Toronto

Chief Medical Officer

MD and MSc in Clinical Epidemiology, University of Toronto

Altaf Stationwala

Unity Health Toronto

Chief Executive Officer

Bachelor's degree in Health Administration, University of Ottawa

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Dr. Paul C. Hébert

Canadian Institutes of Health Research (CIHR)

Chief Executive Officer

MD, University of Ottawa

Dr. Paul C. Hébert

Canadian Institutes of Health Research (CIHR)

Chief Medical Officer

MD, University of Ottawa

University of Toronto

Collaborator

Trials

739

Recruited

1,125,000+

Allison Brown

University of Toronto

Chief Medical Officer

PhD in Chemical Engineering from the University of Toronto

Michael Sefton

University of Toronto

Chief Executive Officer since 2017

PhD in Chemical Engineering from the University of Toronto and MIT

Applied Health Research Centre

Collaborator

Trials

23

Recruited

70,900+

Findings from Research

Adopting lung-protective ventilatory strategies that limit ventilator-induced lung injury and allow for permissive hypercapnia has shown a significant reduction in mortality rates for patients with acute respiratory distress syndrome (ARDS).

There is a growing consensus in the medical community to consistently apply these protective strategies in mechanical ventilation, which may lead to improved outcomes and lower mortality rates in ARDS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategies of invasive ventilatory support in ARDS. Kirkpatrick, AW., Meade, MO., Mustard, RA., et al.[2020]

Advancements in treating respiratory failure over the past 20 years focus on optimizing oxygenation while reducing the risk of lung injury from mechanical ventilation, emphasizing the importance of ventilation modes and strategies.

Salvage therapies like prone positioning and inhaled medications can enhance oxygen delivery, but they do not necessarily improve survival rates, highlighting the complexity of managing acute respiratory distress syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanical ventilation. James, MM., Beilman, GJ.[2020]

Current strategies for treating acute respiratory distress syndrome (ARDS) focus on minimizing ventilation-induced lung injury (VILI) by personalizing mechanical ventilation based on individual patient respiratory mechanics.

Understanding the specific biophysical mechanisms of VILI, such as volutrauma and barotrauma, allows for better assessment and tailoring of lung-protective ventilation strategies, potentially reducing the risk of multiorgan failure associated with ARDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bedside respiratory physiology to detect risk of lung injury in acute respiratory distress syndrome. Beitler, JR.[2020]

Acute respiratory distress syndrome (ARDS) is not a single disease but a collection of conditions leading to lung injury, making treatment evaluation challenging.

Using lower tidal volumes and lower plateau pressures during ventilation has been associated with reduced mortality in ARDS patients, while high tidal volumes can worsen outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ventilatory strategies and adjunctive therapy in ARDS. Desai, AR., Deep, A.[2020]

A recent study involving over 800 patients confirmed that a ventilatory strategy using low volumes and positive end-expiratory pressure can improve outcomes in patients with acute respiratory distress syndrome (ARDS).

This approach helps to limit lung distension and recruit collapsed lung areas, addressing the mechanical ventilation challenges that can lead to further lung injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Acute respiratory distress syndrome]. Richard, JC.[2020]

In a study of 120 patients at high risk for acute respiratory distress syndrome, a limited-ventilation strategy did not significantly reduce mortality compared to conventional ventilation, with mortality rates of 50% and 47% respectively.

The limited-ventilation group experienced more permissive hypercapnia and required more interventions, such as paralytic agents and dialysis for renal failure, suggesting that this approach may increase morbidity without improving survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of a ventilation strategy to prevent barotrauma in patients at high risk for acute respiratory distress syndrome. Pressure- and Volume-Limited Ventilation Strategy Group. Stewart, TE., Meade, MO., Cook, DJ., et al.[2022]

In managing mechanical ventilation for acute lung injury and acute respiratory distress syndrome, understanding the underlying lung pathology is crucial for determining the potential for lung recruitment, which can be high when lung collapse exceeds consolidation.

Key strategies for effective ventilation include applying sufficient transpulmonary pressure to recruit collapsed lung units, using positive end-expiratory pressure to prevent collapse, and maintaining low airway pressures to avoid lung injury, emphasizing the importance of gentle treatment of the lungs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physiologic rationale for ventilator setting in acute lung injury/acute respiratory distress syndrome patients. Gattinoni, L., Vagginelli, F., Chiumello, D., et al.[2020]

Recent advancements in understanding ARDS (Acute Respiratory Distress Syndrome) have led to improved survival rates by focusing on strategies that prevent lung injury caused by mechanical ventilation.

To minimize damage, it is crucial for physicians to ventilate ARDS patients within safe pressure limits, specifically avoiding peak inspiratory pressures above 40 cm H2O and allowing the lungs to rest.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ventilation in the trauma and surgical patient. Battistella, FD.[2020]

Mechanical ventilation for acute respiratory distress syndrome (ARDS) focuses on preventing lung overdistention by using small tidal volumes and adjusting positive end-expiratory pressure (PEEP) to improve lung recruitment.

When standard ventilation strategies are not effective, additional rescue therapies such as extracorporeal therapies and high-frequency oscillatory ventilation may be employed to enhance gas exchange in patients with severe ARDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing Acute Lung Injury. Schmidt, GA.[2020]

Lung protective strategies for managing acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) focus on using smaller tidal volumes and adjusting positive end-expiratory pressure to prevent ventilator-induced lung injury (VILI).

Individualized ventilatory management is crucial, as no single technique is optimal for all patients; strategies like prone positioning and high frequency ventilation may be beneficial depending on the patient's specific lung mechanics and gas exchange needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanical ventilation of patients with acute lung injury. Sessler, CN.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Strategies of invasive ventilatory support in ARDS. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Mechanical ventilation. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Bedside respiratory physiology to detect risk of lung injury in acute respiratory distress syndrome. [2020]

4. India pubmed.ncbi.nlm.nih.gov

Ventilatory strategies and adjunctive therapy in ARDS. [2020]

5. France pubmed.ncbi.nlm.nih.gov

[Acute respiratory distress syndrome]. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Evaluation of a ventilation strategy to prevent barotrauma in patients at high risk for acute respiratory distress syndrome. Pressure- and Volume-Limited Ventilation Strategy Group. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Physiologic rationale for ventilator setting in acute lung injury/acute respiratory distress syndrome patients. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Ventilation in the trauma and surgical patient. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Managing Acute Lung Injury. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Mechanical ventilation of patients with acute lung injury. [2020]