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Careful Ventilation in Acute Respiratory Distress Syndrome (CAVIARDS)

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ClinicalTrials.gov Identifier: NCT03963622
Recruitment Status : Not yet recruiting
First Posted : May 24, 2019
Last Update Posted : May 24, 2019
Sponsor:
Information provided by (Responsible Party):
St. Michael's Hospital, Toronto

Brief Summary:
This is a multicenter randomized controlled pilot trial to investigate the feasibility of assessing respiratory mechanics to individualize ventilation parameters compared to a conventional ventilation strategy in patients with acute respiratory distress syndrome (ARDS).

Condition or disease Intervention/treatment Phase
ARDS Other: Respiratory Mechanics Other: Standard Ventilation Strategy Not Applicable

Detailed Description:

Acute respiratory distress syndrome (ARDS) is a major public health problem affecting approximately 10% of patients in the intensive care unit (ICU) and 23% of all patients on a breathing machine (mechanical ventilator). The short-term mortality of patients with ARDS is approximately 40% and better ventilation of these patients has the greatest potential to improve outcomes.

The lungs in patients with ARDS are severely inflamed which reduces lung volume and their ability to stretch, making ventilation difficult and dangerous. However, mechanical ventilation is the mainstay of supportive therapy. Although it is life-saving, it can also can generate secondary injury and inflammation, called ventilator-induced lung injury (VILI). The investigators know that inadequate mechanical ventilation worsens outcomes but are uncertain of the optimal way to manage ventilators at the bedside.

Furthermore, ARDS is challenging because there is no treatment for the alveolar-capillary leak characterizing this syndrome; aside from treating the underlying cause, the only supportive therapy is mechanical ventilation. Despite best practices, over-distension of the lung or inappropriate positive end expiratory pressure (PEEP) is common. Finally, once spontaneous breathing has resumed and is assisted by the ventilator, an additional phenomenon occurs, called patient self-inflicted lung injury. The drive for breathing in many patients is stimulated by lung inflammation, and strong breathing efforts can generate high distending pressures, causing lung (and systemic) inflammation and organ damage.

Recent advances in our understanding of bedside physiology (airway closure, recruitability, lung distension) can now be applied for an individual titration of mechanical ventilation.

This study aims to reduce the risk of injury by controlling three risk factors. The investigators will individualize each of these factors to the patient in an attempt to reduce the mortality associated with ARDS.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: CAreful Ventilation In ARDS - The CAVIARDS Trial
Estimated Study Start Date : August 2019
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : August 2021


Arm Intervention/treatment
Active Comparator: Control
Standard ventilation strategy.
Other: Standard Ventilation Strategy
Patients randomized to the control arm will receive standard care. The PEEP is kept relatively low for FiO2≤0.7 and is adjusted for oxygenation based on a PEEP-FiO2 table. Standard simple conventional mechanics, routinely available on contemporary ventilators (no esophageal manometry) are recorded, but not used per protocol. Volume targeted ventilation with initial VT 6 mL·kg-1 and Plateau pressure at 30 cmH2O or below, targeting PaO2 60-80 or SpO2 90-95%, adjusted as per the protocol. Pressure-support ventilation is at physician's discretion, but recommended when FiO2 <60%, and is titrated VT 6-8 mL·kg-1.

Experimental: Respiratory Mechanics
The goal of this arm is to individualize tidal volume (VT) and PEEP according to respiratory mechanics.
Other: Respiratory Mechanics

Respiratory mechanics will be assessed at the bedside and will be used to individualize ventilator parameters. Recruitability will be assessed with a one breath decremental PEEP maneuver, and search for airway closure with a low-flow pressure volume curve. If the patient has airway closure, the minimal PEEP will be set at the airway opening pressure to avoid closure. If the patient is considered recruitable, the goal is to set PEEP at or above 15cmH20 to maximize alveolar recruitment, until the plateau transpulmonary pressure reaches the safety limit. Volume control ventilation at 6ml·kg-1 will be used.

Once spontaneous breathing has started, the swing in transpulmonary pressure will be limited.





Primary Outcome Measures :
  1. Adherence to the mechanical ventilation protocols without major violations [ Time Frame: 7 days ]

    Adherence will be met if more than 75% of patients have fewer than 2 major protocol violations. Major violations are defined as follows:

    For patients in the experimental arm:

    • Airway closure not assessed;
    • Lung recruitability not assessed;
    • PEEP not set according to the protocol;
    • Transpulmonary plateau pressure not measured;
    • Driving pressure not measured;
    • Pes placement failure;
    • Transpulmonary pressure swings not measured;

    For patients in the control arm:

    • PEEP does not match the ARDSnet low PEEP-FiO2 table;
    • FiO2 does not match the ARDSnet low PEEP-FiO2 table;
    • Plateau pressure not measured.


Secondary Outcome Measures :
  1. Ventilator free days at 28 days post randomization [ Time Frame: 28 days ]
  2. Duration of ICU and hospital stay [ Time Frame: Duration of ICU and hospital stay which may exceed 60 days ]
  3. Number of patients with organ dysfunction [ Time Frame: Day 3 and Day 7 ]
  4. Number of patients with barotrauma [ Time Frame: Up to 7 days ]
  5. Mortality at ICU and hospital discharge [ Time Frame: Up to ICU or hospital discharge ]
  6. Mortality at 28 and 60 days [ Time Frame: Day 28 and Day 60 ]

Other Outcome Measures:
  1. The change in biomarker expression [ Time Frame: Baseline, 24 and 72 hours ]
    Biomarkers include interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor receptor 1 (TNFr1), soluble receptor of the advanced glycation end products (sRAGE), and surfactant protein D (SPD). All measured in pg/ml



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 y
  • Moderate or severe ARDS (PaO2/FiO2 ≤ 200mmHg) within 48 h of meeting Berlin ARDS criteria

Exclusion Criteria:

  • Mechanical ventilation > 7 days (continuously)
  • Contra-indication to esophageal manometry
  • Raised intracranial pressure (>18mmHg)
  • Other contraindications to hypercapnia
  • Pregnancy
  • Broncho-pleural fistula
  • History or plan for lung transplant
  • Severe liver disease (Child-Pugh Score ≥ 10)
  • Anticipating withdrawal of life support and/or shift to palliation as the goal of care
  • BMI >40kg/m2

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03963622


Contacts
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Contact: Laurent Brochard, MD 416-864-6060 ext 5686 BrochardL@smh.ca

Sponsors and Collaborators
St. Michael's Hospital, Toronto

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Responsible Party: St. Michael's Hospital, Toronto
ClinicalTrials.gov Identifier: NCT03963622     History of Changes
Other Study ID Numbers: 1765
First Posted: May 24, 2019    Key Record Dates
Last Update Posted: May 24, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by St. Michael's Hospital, Toronto:
Ventilation
ARDS
Esophageal manometry
Airway closure
Lung recruitment

Additional relevant MeSH terms:
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Respiratory Distress Syndrome, Adult
Acute Lung Injury
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Lung Injury