Ventilation prudente dans le syndrome de détresse respiratoire aiguë (COVID-19 et non-COVID-19) (CAVIARDS)
Ventilation prudente dans le syndrome de détresse respiratoire aiguë
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.).
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
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.
Type d'étude
Inscription (Estimé)
Phase
- N'est pas applicable
Contacts et emplacements
Coordonnées de l'étude
- Nom: Laurent Brochard, MD
- Numéro de téléphone: 5686 416-864-6060
- E-mail: laurent.brochard@unityhealth.to
Lieux d'étude
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Buenos Aires, Argentine
- Recrutement
- Hospital Británico de Buenos Aires
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Contact:
- Gustavo Plotnikov, RRT
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Buenos Aires, Argentine
- Recrutement
- Complejo Médico Policía Federal Argentina Churruca Visca
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Contact:
- Maria Guaymas, MD
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Buenos Aires, Argentine
- Recrutement
- Sanatorio Anchorena Recoleta
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Contact:
- Daniela Vasquez, MD
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Buenos Aires, Argentine
- Recrutement
- Sanatorio Mater Dei
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Contact:
- Magalí Gutiérrez, MD
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Buenos Aires, Argentine
- Recrutement
- Centro de Educación Médica e Investigaciones Clínicas Dr Norberto Quirno (CEMIC)
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Contact:
- Pablo Rodriguez, MD
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San Martin, Argentine
- Recrutement
- Sanatorio Anchorena San Martín
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Contact:
- Matias Accoce, RRT
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Toronto, Canada
- Recrutement
- St. Michael's Hospital
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Contact:
- Laurent Brochard, MD
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Toronto, Canada
- Recrutement
- Toronto General Hospital
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Contact:
- Ewan Goligher, MD
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Toronto, Canada
- Recrutement
- Toronto Western Hospital
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Contact:
- Irene Telias, MD
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Santiago, Chili
- Recrutement
- Pontificia Universidad Católica de Chile
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Contact:
- Felipe Damiani, PhD
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Barcelona, Espagne
- Recrutement
- Vall d'Hebron University Hospital
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Contact:
- Andres F Pacheco, MD
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Barcelona, Espagne
- Recrutement
- L'Hospital de la Santa Creu i Sant Pau
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Contact:
- Marta I Gomez, MD
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Amiens, France
- Recrutement
- CHU Amiens-Picardie
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Contact:
- Michel Slama, MD
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Angers, France
- Recrutement
- Centre hospitalier universitaire d'Angers
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Contact:
- Francois Beloncle, MD
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Argenteuil, France
- Recrutement
- CH Victor Dupouy
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Contact:
- Gaetan Plantefeve, MD
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Beauvais, France
- Recrutement
- CH de Beauvais
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Contact:
- Jack Richecoeur, MD
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Bordeaux, France
- Recrutement
- CHU Bordeaux - Haut Leveque
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Contact:
- Benjamin Repusseau, MD
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Brest, France
- Recrutement
- Hopital de la Cavale Blanche - CHRU Brest
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Contact:
- Gwenael Prat, MD
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Cholet, France
- Recrutement
- CH de Cholet
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Contact:
- Johann Auchabie, MD
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Créteil, France
- Recrutement
- Hopital Intercommunal de Creteil
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Contact:
- Tommaso Maraffi, MD
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Grenoble, France
- Recrutement
- CHU Grenoble-Alpes
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Contact:
- Florian Sigaud, MD
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Lille, France
- Recrutement
- Hopital Roger Salengro - CHU Lille
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Contact:
- Saad Nseir, MD
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Mulhouse, France
- Recrutement
- Groupe Hospitalier de la Region de Mulhouse et Sud Alsace
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Contact:
- Khaldoun Kuteifan, MD
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Nice, France
- Recrutement
- Hopital de l'Archet 1 - CHU de Nice
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Contact:
- Jean Dellamonica, MD
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Paris, France
- Recrutement
- Hopital Europeen Georges-Pompidou
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Contact:
- Jean-Luc Diehl, MD
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Poitiers, France
- Recrutement
- CHU de Poitiers - La Miletrie
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Contact:
- Remi Coudroy, MD
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Vannes, France
- Recrutement
- CH Bretagne Atlantique Vannes-Auray
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Contact:
- Agathe Delbove, MD
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Villenave-d'Ornon, France
- Recrutement
- HIA Robert Picque
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Contact:
- David Tran-Van, MD
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Ferrara, Italie
- Recrutement
- Arcispedale Sant'Anna
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Contact:
- Savino Spadaro, MD
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Foggia, Italie
- Recrutement
- University of Foggia
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Contact:
- Michela Rauseo, MD
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Rome, Italie
- Recrutement
- Policlinico Universitario Agostino Gemelli IRCCS
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Contact:
- Domenico L Grieco, MD
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North Holland
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Amsterdam, North Holland, Pays-Bas
- Recrutement
- OLVG
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Contact:
- Rogier Determann, MD
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New York
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New York, New York, États-Unis, 10016
- Recrutement
- New York University Grossman School of Medicine
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Contact:
- David Kaufman, MD
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Seul
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Comparateur actif: Control
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. |
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Expérimental: Respiratory Mechanics
The goal of this arm is to individualize tidal volume (VT) and PEEP according to 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. |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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All-cause 60-day mortality
Délai: 60 days
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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. |
60 days
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
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Duration of ventilation
Délai: May exceed 60 days
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Duration of ventilation in days |
May exceed 60 days
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Duration of ICU and hospital stay
Délai: May exceed 60 days
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Duration of ICU and hospital stay in days |
May exceed 60 days
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Number of patients with organ dysfunction
Délai: Day 1-7, 14, 21, 28
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Organ dysfunction as per the SOFA score |
Day 1-7, 14, 21, 28
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Number of patients with barotrauma
Délai: Up to 60 days
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Barotrauma defined as new onset of pneumothorax |
Up to 60 days
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Mortality at ICU discharge, 28 days, and hospital discharge
Délai: Up to date of ICU discharge, 28 days, and hospital discharge
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Mortality |
Up to date of ICU discharge, 28 days, and hospital discharge
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Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
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The change in biomarker expression
Délai: Baseline, 24 and 72 hours
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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 |
Baseline, 24 and 72 hours
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Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Laurent Brochard, MD, Unity Health Toronto
Publications et liens utiles
Publications générales
- 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.
- 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.
Liens utiles
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Processus pathologiques
- Infections des voies respiratoires
- Infections
- Infections par virus à ARN
- Maladies virales
- Maladies des voies respiratoires
- Maladies pulmonaires
- Troubles respiratoires
- Pneumonie virale
- Pneumonie
- Infections à coronavirus
- Infections à Coronaviridae
- Infections à Nidovirales
- Conditions pathologiques, signes et symptômes
- COVID-19 [feminine]
- Aspiration respiratoire
- Phénomènes physiologiques circulatoires et respiratoires
- Respiration
- Phénomènes physiologiques respiratoires
- Mécanique respiratoire
Autres numéros d'identification d'étude
- 1765
Plan pour les données individuelles des participants (IPD)
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Description du régime IPD
The final anonymized trial dataset will be available on reasonable written request to the principal investigator one year after publication of the main manuscript.
Informations sur les médicaments et les dispositifs, documents d'étude
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