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

NCT ID: NCT03963622

Last Updated: 2026-01-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

740 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-11-23

Study Completion Date

2026-09-30

Brief Summary

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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.).

Detailed Description

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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.

Conditions

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ARDS

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This study is also a basket design, which examines a single intervention in multiple disease populations. This basket trial consists of an identical 2-arm mechanical ventilation protocol implemented in two different study populations (patients with COVID-19-induced ARDS, and patients with all ARDS not induced by COVID-19). The protocol and procedures are identical between the two study populations in this basket trial.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Control

Standard ventilation strategy.

Group Type ACTIVE_COMPARATOR

Standard Ventilation Strategy

Intervention Type 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.

Respiratory Mechanics

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

Group Type EXPERIMENTAL

Respiratory Mechanics

Intervention Type 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.

Interventions

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Respiratory Mechanics

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.

Intervention Type OTHER

Standard Ventilation Strategy

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.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Age ≥ 18 y
2. 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

1. Received continuous mechanical ventilation \> 7 days
2. Known or clinically suspected elevated intracranial pressure (\>18mmHg) necessitating strict 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 of care
8. Patient is receiving ECMO at time of randomization
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role collaborator

University of Toronto

OTHER

Sponsor Role collaborator

Applied Health Research Centre

OTHER

Sponsor Role collaborator

Unity Health Toronto

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Laurent Brochard, MD

Role: PRINCIPAL_INVESTIGATOR

Unity Health Toronto

Locations

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New York University Grossman School of Medicine

New York, New York, United States

Site Status RECRUITING

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

Buenos Aires, , Argentina

Site Status RECRUITING

Complejo Médico Policía Federal Argentina Churruca Visca

Buenos Aires, , Argentina

Site Status RECRUITING

Hospital Británico de Buenos Aires

Buenos Aires, , Argentina

Site Status RECRUITING

Sanatorio Anchorena Recoleta

Buenos Aires, , Argentina

Site Status RECRUITING

Sanatorio Mater Dei

Buenos Aires, , Argentina

Site Status RECRUITING

Sanatorio Anchorena San Martín

San Martín, , Argentina

Site Status RECRUITING

St. Michael's Hospital

Toronto, , Canada

Site Status RECRUITING

Toronto General Hospital

Toronto, , Canada

Site Status RECRUITING

Toronto Western Hospital

Toronto, , Canada

Site Status RECRUITING

Pontificia Universidad Católica de Chile

Santiago, , Chile

Site Status RECRUITING

CHU Amiens-Picardie

Amiens, , France

Site Status RECRUITING

Centre hospitalier universitaire d'Angers

Angers, , France

Site Status RECRUITING

CH Victor Dupouy

Argenteuil, , France

Site Status RECRUITING

CH de Beauvais

Beauvais, , France

Site Status RECRUITING

CHU Bordeaux - Haut Leveque

Bordeaux, , France

Site Status RECRUITING

Hopital de la Cavale Blanche - CHRU Brest

Brest, , France

Site Status RECRUITING

CH de Cholet

Cholet, , France

Site Status RECRUITING

Hopital Intercommunal de Creteil

Créteil, , France

Site Status RECRUITING

CHU Grenoble-Alpes

Grenoble, , France

Site Status RECRUITING

Hopital Roger Salengro - CHU Lille

Lille, , France

Site Status RECRUITING

Groupe Hospitalier de la Region de Mulhouse et Sud Alsace

Mulhouse, , France

Site Status RECRUITING

Hopital de l'Archet 1 - CHU de Nice

Nice, , France

Site Status RECRUITING

Hopital Europeen Georges-Pompidou

Paris, , France

Site Status RECRUITING

CHU de Poitiers - La Miletrie

Poitiers, , France

Site Status RECRUITING

CH Bretagne Atlantique Vannes-Auray

Vannes, , France

Site Status RECRUITING

HIA Robert Picque

Villenave-d'Ornon, , France

Site Status RECRUITING

Arcispedale Sant'Anna

Ferrara, , Italy

Site Status RECRUITING

University of Foggia

Foggia, , Italy

Site Status RECRUITING

Policlinico Universitario Agostino Gemelli IRCCS

Rome, , Italy

Site Status RECRUITING

OLVG

Amsterdam, North Holland, Netherlands

Site Status RECRUITING

L'Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Site Status RECRUITING

Vall d'Hebron University Hospital

Barcelona, , Spain

Site Status RECRUITING

Countries

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United States Argentina Canada Chile France Italy Netherlands Spain

Central Contacts

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Laurent Brochard, MD

Role: CONTACT

416-864-6060 ext. 5686

Facility Contacts

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David Kaufman, MD

Role: primary

Pablo Rodriguez, MD

Role: primary

Maria Guaymas, MD

Role: primary

Gustavo Plotnikov, RRT

Role: primary

Daniela Vasquez, MD

Role: primary

Magalí Gutiérrez, MD

Role: primary

Matias Accoce, RRT

Role: primary

Laurent Brochard, MD

Role: primary

Ewan Goligher, MD

Role: primary

Irene Telias, MD

Role: primary

Felipe Damiani, PhD

Role: primary

Michel Slama, MD

Role: primary

Francois Beloncle, MD

Role: primary

Gaetan Plantefeve, MD

Role: primary

Jack Richecoeur, MD

Role: primary

Benjamin Repusseau, MD

Role: primary

Gwenael Prat, MD

Role: primary

Johann Auchabie, MD

Role: primary

Tommaso Maraffi, MD

Role: primary

Florian Sigaud, MD

Role: primary

Saad Nseir, MD

Role: primary

Khaldoun Kuteifan, MD

Role: primary

Jean Dellamonica, MD

Role: primary

Jean-Luc Diehl, MD

Role: primary

Remi Coudroy, MD

Role: primary

Agathe Delbove, MD

Role: primary

David Tran-Van, MD

Role: primary

Savino Spadaro, MD

Role: primary

Michela Rauseo, MD

Role: primary

Domenico L Grieco, MD

Role: primary

Rogier Determann, MD

Role: primary

Marta I Gomez, MD

Role: primary

Andres F Pacheco, MD

Role: primary

References

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Villalba DS, Matesa A, Boni S, Gutierrez FJ, Moracci R, Plotnikow GA. Impact of High-Flow Nasal Cannula Oxygen Therapy on the Pressure of the Airway System in Humans. Respir Care. 2025 Jan;70(1):10-16. doi: 10.1089/respcare.12082.

Reference Type DERIVED
PMID: 39964860 (View on PubMed)

Related Links

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Other Identifiers

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1765

Identifier Type: -

Identifier Source: org_study_id

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