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

Last updated: January 14, 2026
Sponsor: Unity Health Toronto
Overall Status: Active - Recruiting

Phase

N/A

Condition

Lung Injury

Covid-19

Acute Respiratory Distress Syndrome (Ards)

Treatment

Standard Ventilation Strategy

Respiratory Mechanics

Clinical Study ID

NCT03963622
1765
  • Ages > 18
  • All Genders

Study Summary

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.).

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Age ≥ 18 y

  2. Moderate or severe ARDS (PaO2/FiO2 ≤ 200 mmHg) within 48 h of meeting Berlin ARDScriteria (Patients who were eligible at the time of screening and whose PaO2/FiO2became > 200 mm Hg under prone positioning when starting the protocol remainedeligible)

Exclusion

Exclusion Criteria:

  1. Received continuous mechanical ventilation > 7 days

  2. Known or clinically suspected elevated intracranial pressure (>18mmHg) necessitatingstrict control of PaCO2

  3. Known pregnancy

  4. Broncho-pleural fistula

  5. Severe liver disease (Child-Pugh Score ≥ 10)

  6. BMI >40kg/m2

  7. Anticipating withdrawal of life support and/or shift to palliation as the goal ofcare

  8. Patient is receiving ECMO at time of randomization

Study Design

Total Participants: 740
Treatment Group(s): 2
Primary Treatment: Standard Ventilation Strategy
Phase:
Study Start date:
November 23, 2020
Estimated Completion Date:
September 30, 2026

Study 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. 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.

Connect with a study center

  • Centro de Educación Médica e Investigaciones Clínicas Dr Norberto Quirno (CEMIC)

    Buenos Aires,
    Argentina

    Site Not Available

  • Complejo Médico Policía Federal Argentina Churruca Visca

    Buenos Aires,
    Argentina

    Active - Recruiting

  • Hospital Británico de Buenos Aires

    Buenos Aires,
    Argentina

    Active - Recruiting

  • Sanatorio Anchorena Recoleta

    Buenos Aires,
    Argentina

    Active - Recruiting

  • Sanatorio Mater Dei

    Buenos Aires,
    Argentina

    Active - Recruiting

  • Centro de Educación Médica e Investigaciones Clínicas Dr Norberto Quirno (CEMIC)

    Buenos Aires 3435910,
    Argentina

    Active - Recruiting

  • Complejo Médico Policía Federal Argentina Churruca Visca

    Buenos Aires 3435910,
    Argentina

    Active - Recruiting

  • Hospital Británico de Buenos Aires

    Buenos Aires 3435910,
    Argentina

    Active - Recruiting

  • Sanatorio Anchorena Recoleta

    Buenos Aires 3435910,
    Argentina

    Active - Recruiting

  • Sanatorio Mater Dei

    Buenos Aires 3435910,
    Argentina

    Active - Recruiting

  • Sanatorio Anchorena San Martín

    San Martín,
    Argentina

    Site Not Available

  • Sanatorio Anchorena San Martín

    San Martín 3836992,
    Argentina

    Active - Recruiting

  • St. Michael's Hospital

    Toronto,
    Canada

    Site Not Available

  • Toronto General Hospital

    Toronto,
    Canada

    Active - Recruiting

  • Toronto Western Hospital

    Toronto,
    Canada

    Active - Recruiting

  • St. Michael's Hospital

    Toronto 6167865,
    Canada

    Active - Recruiting

  • Toronto General Hospital

    Toronto 6167865,
    Canada

    Active - Recruiting

  • Toronto Western Hospital

    Toronto 6167865,
    Canada

    Active - Recruiting

  • Pontificia Universidad Católica de Chile

    Santiago 3871336,
    Chile

    Active - Recruiting

  • Pontificia Universidad Católica de Chile

    Santiago de Chile,
    Chile

    Site Not Available

  • CHU Amiens-Picardie

    Amiens,
    France

    Site Not Available

  • CHU Amiens-Picardie

    Amiens 3037854,
    France

    Active - Recruiting

  • Centre hospitalier universitaire d'Angers

    Angers,
    France

    Site Not Available

  • Centre hospitalier universitaire d'Angers

    Angers 3037656,
    France

    Active - Recruiting

  • CH Victor Dupouy

    Argenteuil,
    France

    Site Not Available

  • CH Victor Dupouy

    Argenteuil 3037044,
    France

    Active - Recruiting

  • CH de Beauvais

    Beauvais,
    France

    Site Not Available

  • CH de Beauvais

    Beauvais 3034006,
    France

    Active - Recruiting

  • CHU Bordeaux - Haut Leveque

    Bordeaux,
    France

    Site Not Available

  • CHU Bordeaux - Haut Leveque

    Bordeaux 3031582,
    France

    Active - Recruiting

  • Hopital de la Cavale Blanche - CHRU Brest

    Brest,
    France

    Site Not Available

  • Hopital de la Cavale Blanche - CHRU Brest

    Brest 3030300,
    France

    Active - Recruiting

  • CH de Cholet

    Cholet,
    France

    Site Not Available

  • CH de Cholet

    Cholet 3025053,
    France

    Active - Recruiting

  • Hopital Intercommunal de Creteil

    Creteil,
    France

    Site Not Available

  • Hopital Intercommunal de Creteil

    Créteil 3022530,
    France

    Active - Recruiting

  • CHU Grenoble-Alpes

    Grenoble,
    France

    Site Not Available

  • CHU Grenoble-Alpes

    Grenoble 3014728,
    France

    Active - Recruiting

  • Hopital Roger Salengro - CHU Lille

    Lille,
    France

    Site Not Available

  • Hopital Roger Salengro - CHU Lille

    Lille 2998324,
    France

    Active - Recruiting

  • Groupe Hospitalier de la Region de Mulhouse et Sud Alsace

    Mulhouse,
    France

    Site Not Available

  • Groupe Hospitalier de la Region de Mulhouse et Sud Alsace

    Mulhouse 2991214,
    France

    Active - Recruiting

  • Hopital de l'Archet 1 - CHU de Nice

    Nice,
    France

    Site Not Available

  • Hopital de l'Archet 1 - CHU de Nice

    Nice 2990440,
    France

    Active - Recruiting

  • Hopital Europeen Georges-Pompidou

    Paris,
    France

    Site Not Available

  • Hopital Europeen Georges-Pompidou

    Paris 2988507,
    France

    Active - Recruiting

  • CHU de Poitiers - La Miletrie

    Poitiers,
    France

    Site Not Available

  • CHU de Poitiers - La Miletrie

    Poitiers 2986495,
    France

    Active - Recruiting

  • CH Bretagne Atlantique Vannes-Auray

    Vannes,
    France

    Site Not Available

  • CH Bretagne Atlantique Vannes-Auray

    Vannes 2970777,
    France

    Active - Recruiting

  • HIA Robert Picque

    Villenave-d'Ornon,
    France

    Site Not Available

  • HIA Robert Picque

    Villenave-d'Ornon 2968620,
    France

    Active - Recruiting

  • Arcispedale Sant'Anna

    Ferrara,
    Italy

    Site Not Available

  • Arcispedale Sant'Anna

    Ferrara 3177090,
    Italy

    Active - Recruiting

  • University of Foggia

    Foggia,
    Italy

    Site Not Available

  • University of Foggia

    Foggia 3176885,
    Italy

    Active - Recruiting

  • Policlinico Universitario Agostino Gemelli IRCCS

    Rome,
    Italy

    Site Not Available

  • Policlinico Universitario Agostino Gemelli IRCCS

    Rome 3169070,
    Italy

    Active - Recruiting

  • OLVG

    Amsterdam 2759794, North Holland 2749879
    Netherlands

    Active - Recruiting

  • L'Hospital de la Santa Creu i Sant Pau

    Barcelona,
    Spain

    Site Not Available

  • Vall d'Hebron University Hospital

    Barcelona,
    Spain

    Active - Recruiting

  • L'Hospital de la Santa Creu i Sant Pau

    Barcelona 3128760,
    Spain

    Active - Recruiting

  • Vall d'Hebron University Hospital

    Barcelona 3128760,
    Spain

    Active - Recruiting

  • New York University Grossman School of Medicine

    New York, New York 10016
    United States

    Site Not Available

  • New York University Grossman School of Medicine

    New York 5128581, New York 5128638 10016
    United States

    Active - Recruiting

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