Ventilation Strategy for Acute Respiratory Distress Syndrome

(CAVIARDS Trial)

Recruiting at 33 trial locations

Overseen By Laurent Brochard, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Unity Health Toronto

Disqualifiers: Pregnancy, Severe liver disease, ECMO, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 60 days

740 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of using ventilators for individuals with acute respiratory distress syndrome (ARDS), a severe breathing condition. The researchers aim to determine if adjusting the ventilator based on lung response, known as Respiratory Mechanics, can reduce mortality by Day 60. The trial includes both COVID-19 patients and those with other causes of ARDS. Participants must have experienced ARDS for less than two days and face significant breathing difficulties. As an unphased study, this trial provides a unique opportunity to contribute to innovative research that could enhance treatment for ARDS patients.

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 prior data suggests that this ventilation strategy is safe for patients with acute respiratory distress syndrome?

Research shows that adjusting ventilator settings based on lung function can benefit people with acute respiratory distress syndrome (ARDS). Studies have found that personalized ventilation often leads to better patient outcomes by tailoring ventilator settings to the specific needs of the patient's lungs.

In these studies, patients who received personalized ventilation often experienced improved results. For example, those requiring higher PEEP (a ventilator setting) and receiving it had a lower risk of death. Personalized approaches appear safe, with no major safety issues reported.

Overall, while more research is always beneficial, current evidence supports the safety of using lung function to guide ventilation settings. This approach could be a good option for those considering participation in a trial like this one. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the trial exploring a new ventilation strategy for Acute Respiratory Distress Syndrome (ARDS) because it aims to personalize treatment. Unlike the standard approach, which uses a one-size-fits-all method for setting tidal volume and PEEP (positive end-expiratory pressure), this new strategy tailors these settings based on individual respiratory mechanics. By customizing ventilation, the goal is to optimize lung function and potentially improve outcomes for patients with ARDS.

What evidence suggests that this trial's ventilation strategies could be effective for ARDS?

This trial will compare two ventilation strategies for acute respiratory distress syndrome (ARDS). Participants in the control arm will receive the standard ventilation strategy, which uses lower tidal volumes and maintains specific pressure levels in the lungs. Research has shown that this approach can significantly reduce death rates. Meanwhile, participants in the experimental arm will have ventilator settings customized based on their individual respiratory mechanics. Studies suggest that adjusting ventilators according to a patient's lung function might help reduce deaths in people with ARDS, including those with COVID-19. ^{3 6 7 8 9}

Who Is on the Research Team?

Laurent Brochard, MD

Principal Investigator

Unity Health Toronto

Are You a Good Fit for This Trial?

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 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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Respiratory Mechanics
• Standard Ventilation Strategy

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.

How Is the Trial Designed?

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+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

University of Toronto

Collaborator

Trials

739

Recruited

1,125,000+

Applied Health Research Centre

Collaborator

Trials

23

Recruited

70,900+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8157117/

Acute Respiratory Distress Syndrome: Ventilator Management ... This review describes the management of mechanical ventilation in patients with acute respiratory distress syndrome, including in those with coronavirus ...

2. nature.com nature.com/articles/s41392-025-02127-9

Advances in acute respiratory distress syndrome High-flow nasal cannula oxygen has gained traction over the past decade, in large part due to a multicentre trial showing decreased mortality ...

3. atsjournals.org atsjournals.org/doi/10.1164/rccm.202008-3039OC

American Journal of Respiratory and Critical Care Medicine Conclusions: These findings suggest that combining low Vt with prone ventilation is associated with the greatest reduction in mortality for ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1569904825000655

Revisiting Acute Respiratory Distress Syndrome ventilation ... The trial found that reducing ΔP below 15 cmH2O and, more ideally, below 10 cmH2O, resulted in significant reductions in 30-day ventilator mortality. Notably, ...

5. eurjmedres.biomedcentral.com eurjmedres.biomedcentral.com/articles/10.1186/s40001-023-01577-7

Association of elastic power in mechanical ventilation with the ... This study aimed to investigate whether EP is superior to other ventilator variables for predicting the severity of lung injury in ARDS patients.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6212350/

Respiratory mechanics in patients with acute respiratory ... The low volume ventilation has been recognized as the only method to reduce mortality of ARDS patients and plateau pressure as the lighthouse for delivering ...

7. ccforum.biomedcentral.com ccforum.biomedcentral.com/articles/10.1186/s13054-021-03686-3

Personalized mechanical ventilation in acute respiratory ... The present review discussed the rationale for personalized mechanical ventilation in ARDS, different ventilatory targets, the role of lung ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2667100X21000049

Ten golden rules for individualized mechanical ventilation ... In a secondary analysis of the Lung Open Ventilation Study, patients with ARDS who showed improved oxygenation with high PEEP had a lower risk of death (odds ...

9. atsjournals.org atsjournals.org/doi/10.1164/rccm.201612-2495CI

Fifty Years of Research in ARDS.Respiratory Mechanics ... Three main physiological abnormalities characterize ARDS: hypoxemia; reduced capacity to eliminate CO2; and reduced lung volumes and compliance.