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ARDSCAVIARDSNCT03963622

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

A study testing Respiratory Mechanics and Standard Ventilation Strategy in people with ARDS, run by Unity Health Toronto at 33 sites in 8 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
ARDS
What is being tested?
Respiratory Mechanics and Standard Ventilation Strategy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
740 participants
Where
33 sitesin 8 countries
Study dates
23 Nov 2020to Sep 2026
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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

Trial locations and contacts

33 sites in 8 countries. Contact the study team or a site near you to ask about taking part.

33 sites in 8 countries

France16 sites, 16 recruiting
  • CHU Amiens-Picardie

    Amiens

    Michel Slama, MD

    Recruiting
  • Centre hospitalier universitaire d'Angers

    Angers

    Francois Beloncle, MD

    Recruiting
  • CH Victor Dupouy

    Argenteuil

    Gaetan Plantefeve, MD

    Recruiting
  • CH de Beauvais

    Beauvais

    Jack Richecoeur, MD

    Recruiting
  • CHU Bordeaux - Haut Leveque

    Bordeaux

    Benjamin Repusseau, MD

    Recruiting
  • Hopital de la Cavale Blanche - CHRU Brest

    Brest

    Gwenael Prat, MD

    Recruiting
  • CH de Cholet

    Cholet

    Johann Auchabie, MD

    Recruiting
  • Hopital Intercommunal de Creteil

    Créteil

    Tommaso Maraffi, MD

    Recruiting
  • CHU Grenoble-Alpes

    Grenoble

    Florian Sigaud, MD

    Recruiting
  • Hopital Roger Salengro - CHU Lille

    Lille

    Saad Nseir, MD

    Recruiting
  • Groupe Hospitalier de la Region de Mulhouse et Sud Alsace

    Mulhouse

    Khaldoun Kuteifan, MD

    Recruiting
  • Hopital de l'Archet 1 - CHU de Nice

    Nice

    Jean Dellamonica, MD

    Recruiting
  • Hopital Europeen Georges-Pompidou

    Paris

    Jean-Luc Diehl, MD

    Recruiting
  • CHU de Poitiers - La Miletrie

    Poitiers

    Remi Coudroy, MD

    Recruiting
  • CH Bretagne Atlantique Vannes-Auray

    Vannes

    Agathe Delbove, MD

    Recruiting
  • HIA Robert Picque

    Villenave-d'Ornon

    David Tran-Van, MD

    Recruiting

Other trials in France

Argentina6 sites, 6 recruiting
  • Centro de Educación Médica e Investigaciones Clínicas Dr Norberto Quirno (CEMIC)

    Buenos Aires

    Pablo Rodriguez, MD

    Recruiting
  • Complejo Médico Policía Federal Argentina Churruca Visca

    Buenos Aires

    Maria Guaymas, MD

    Recruiting
  • Hospital Británico de Buenos Aires

    Buenos Aires

    Gustavo Plotnikov, RRT

    Recruiting
  • Sanatorio Anchorena Recoleta

    Buenos Aires

    Daniela Vasquez, MD

    Recruiting
  • Sanatorio Mater Dei

    Buenos Aires

    Magalí Gutiérrez, MD

    Recruiting
  • Sanatorio Anchorena San Martín

    San Martin

    Matias Accoce, RRT

    Recruiting

Other trials in Argentina

Canada3 sites, 3 recruiting
  • St. Michael's Hospital

    Toronto

    Laurent Brochard, MD

    Recruiting
  • Toronto General Hospital

    Toronto

    Ewan Goligher, MD

    Recruiting
  • Toronto Western Hospital

    Toronto

    Irene Telias, MD

    Recruiting

Other trials in Canada

Italy3 sites, 3 recruiting
  • Arcispedale Sant'Anna

    Ferrara

    Savino Spadaro, MD

    Recruiting
  • University of Foggia

    Foggia

    Michela Rauseo, MD

    Recruiting
  • Policlinico Universitario Agostino Gemelli IRCCS

    Rome

    Domenico L Grieco, MD

    Recruiting

Other trials in Italy

Spain2 sites, 2 recruiting
  • L'Hospital de la Santa Creu i Sant Pau

    Barcelona

    Marta I Gomez, MD

    Recruiting
  • Vall d'Hebron University Hospital

    Barcelona

    Andres F Pacheco, MD

    Recruiting

Other trials in Spain

United States1 site, 1 recruiting
  • New York University Grossman School of Medicine

    New York, New York, 10016

    David Kaufman, MD

    Recruiting

Other trials in United States

Chile1 site, 1 recruiting
  • Pontificia Universidad Católica de Chile

    Santiago

    Felipe Damiani, PhD

    Recruiting

Other trials in Chile

Netherlands1 site, 1 recruiting
  • OLVG

    Amsterdam, North Holland

    Rogier Determann, MD

    Recruiting

Other trials in Netherlands

About this study

Official title: Careful Ventilation in Acute Respiratory Distress Syndrome

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.).

Read the 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. 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
ARDS
Being tested
Respiratory Mechanics, Standard Ventilation Strategy
Keywords
Ventilation, ARDS, Airway closure, Lung recruitment, COVID-19, Basket trial
Medical subject headings
Respiratory Aspiration, COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Respiratory MechanicsOther

    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 StrategyOther

    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.

Study groups in NCT03963622
Study groupRoleWhat they receive
ControlActive comparatorStandard ventilation strategy.
Receives: Other: Standard Ventilation Strategy
Respiratory MechanicsExperimentalThe goal of this arm is to individualize tidal volume (VT) and PEEP according to respiratory mechanics.
Receives: Other: Respiratory Mechanics

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. All-cause 60-day mortality

    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.

    Measured: 60 days

Secondary outcomes (5)
  1. Duration of ventilation

    Duration of ventilation in days

    Measured: May exceed 60 days

  2. Duration of ICU and hospital stay

    Duration of ICU and hospital stay in days

    Measured: May exceed 60 days

  3. Number of patients with organ dysfunction

    Organ dysfunction as per the SOFA score

    Measured: Day 1-7, 14, 21, 28

  4. Number of patients with barotrauma

    Barotrauma defined as new onset of pneumothorax

    Measured: Up to 60 days

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

    Mortality

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 May 2019
  2. Study start23 Nov 2020
  3. Primary completionJun 2026 (estimated)
  4. Study completionSep 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
740 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03963622
Sponsor's protocol ID
1765
Acronym
CAVIARDS
Status last verified
Jan 2026
First submitted
6 May 2019
Last updated
16 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: The final anonymized trial dataset will be available on reasonable written request to the principal investigator one year after publication of the main manuscript.

Publications

  • Coudroy R, Telias I, Jonkman A, Thille AW, Diehl JL, Peron N, Ko M, Bourion AA, Tiribelli N, Fredes S, Gutierrez M, Manchado Bruno A, Vasquez DN, Pratto RA, Plotnikow GA, Bianchini F, Accoce M, Dorado J, Spadaro S, La Rosa R, Prat G, Bailly P, Delbove A, Pacheco-Reyes A, Roca O, Kuteifan K, Rouze A, Grieco DL, Izura-Gomez M, Mancebo J, Sigaud F, Terzi N, Saccheri C, Dellamonica J, Richecoeur J, Setten M, Rauseo M, Beloncle F, Repusseau B, Roze H, Tran-Van D, Damiani F, Slama M, Kaufman DA, Maraffi T, Goligher EC, Plantefeve G, Determann R, Giamou M, Pham T, Del Sorbo L, Keown-Stoneman CDG, Nisenbaum R, Thorpe K, Piraino T, Chen L, Juni P, Ferguson ND, Slutsky AS, Brochard L; CAVIARDS study group. Careful ventilation in acute respiratory distress syndrome: the protocol of the CAVIARDS international multicentre randomised basket trial. BMJ Open. 2026 Feb 23;16(2):e115775. doi: 10.1136/bmjopen-2025-115775.

    PubMed 41730551
  • 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.

    PubMed 39964860

Questions about this trial

What is this clinical trial studying?

A study testing Respiratory Mechanics and Standard Ventilation Strategy in people with ARDS, run by Unity Health Toronto at 33 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 16 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in France, Argentina, Canada, Italy, Spain and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Laurent Brochard, MD (416-864-6060 ext. 5686, laurent.brochard@unityhealth.to), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

All-cause 60-day mortality (time frame: 60 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03963622, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2026.

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