Skip to main content
OpenTrials
Recruiting

NCT Number: NCT03963622

Careful Ventilation in Acute Respiratory Distress Syndrome (COVID-19 and Non-COVID-19)

This is a multicenter randomized controlled clinical trial with an adaptive design assessing the efficacy of setting the ventilator based on measurements of respiratory mechanics (recruitability and effort) to reduce Day 60 mortality in patients with acute respiratory distress syndrome (ARDS).

The CAVIARDS study is also a basket trial; a basket trial design examines a single intervention in multiple disease populations. CAVIARDS consists of an identical 2-arm mechanical ventilation protocol implemented in two different study populations (COVID-19 and non-COVID-19 patients). As per a typical basket trial design, the operational structure of both the COVID-19 substudy (CAVIARDS-19) and non-COVID-19 substudy (CAVIARDS-all) is shared (recruitment, procedures, data collection, analysis, management, etc.).

Recruiting

Interested in participating?

Request Info

Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Centro de Educación Médica e Investigaciones Clínicas Dr Norberto Quirno (CEMIC), Buenos Aires, Argentina

Loading trial locations.

About this study

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. This is specially the case for COVID-19 induced ARDS. 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. Whether the management of COVID-19 induced ARDS should differ from all other ARDS has been debated at length but has no clear response

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age ≥ 18 y
  • Moderate or severe ARDS (PaO2/FiO2 ≤ 200 mmHg) within 48 h of meeting Berlin ARDS criteria (Patients who were eligible at the time of screening and whose PaO2/FiO2 became > 200 mm Hg under prone positioning when starting the protocol remained eligible)

Exclusion criteria

  • Received continuous mechanical ventilation > 7 days
  • Known or clinically suspected elevated intracranial pressure (>18mmHg) necessitating strict control of PaCO2
  • Known pregnancy
  • Broncho-pleural fistula
  • Severe liver disease (Child-Pugh Score ≥ 10)
  • BMI >40kg/m2
  • Anticipating withdrawal of life support and/or shift to palliation as the goal of care
  • Patient is receiving ECMO at time of randomization

Treatment and study plan

Respiratory Mechanics

Other

Different maneuvers based on 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 or pressure-time 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 pressure reaches the safety limit. Volume control ventilation at 6ml·kg-1 will be used.

Once spontaneous breathing has started, the occlusion pressure (P0.1) will be maintained within targets.

Standard Ventilation Strategy

Other

Patients randomized to the control arm will receive standard care. The PEEP is adjusted for oxygenation based on a PEEP-FiO2 table, either the low PEEP-FiO2 or the high PEEP-FiO2 table. 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.

Primary outcomes

  1. All-cause 60-day mortality

    Time frame: 60 days

    The lack of an appropriate surrogate endpoint, and the high baseline mortality rate mandate a multicentre RCT to determine the mortality effects of setting the ventilator based on recruitability and effort compared with conventional ventilation.

Secondary outcomes

  1. Duration of ventilation

    Time frame: May exceed 60 days

    Duration of ventilation in days

  2. Duration of ICU and hospital stay

    Time frame: May exceed 60 days

    Duration of ICU and hospital stay in days

  3. Number of patients with organ dysfunction

    Time frame: Day 1-7, 14, 21, 28

    Organ dysfunction as per the SOFA score

  4. Number of patients with barotrauma

    Time frame: Up to 60 days

    Barotrauma defined as new onset of pneumothorax

  5. Mortality at ICU discharge, 28 days, and hospital discharge

    Time frame: Up to date of ICU discharge, 28 days, and hospital discharge

    Mortality

Other outcomes

  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

Study contacts

Contact information is provided by the study sponsor or research team.

Laurent Brochard, MD

CONTACT

[email protected]

416-864-6060 ext. 5686

Sponsors and collaborators

Lead sponsor

Unity Health Toronto

Other

Collaborators

  • Applied Health Research Centre
  • Canadian Institutes of Health Research (CIHR)
  • University of Toronto

Registry information

Official study title

Careful Ventilation in Acute Respiratory Distress Syndrome

Acronym: CAVIARDS

Important dates

Study start
2020
Primary completion
2026
Study completion
2026
First posted
May 24, 2019
Registry last updated
Jan 16, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.