Noggrann ventilation vid akut andnödsyndrom (COVID-19 och icke-COVID-19) (CAVIARDS)
Noggrann ventilation vid akut andnödssyndrom
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.).
Studieöversikt
Status
Betingelser
Intervention / Behandling
Detaljerad beskrivning
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.
Studietyp
Inskrivning (Beräknad)
Fas
- Inte tillämpbar
Kontakter och platser
Studiekontakt
- Namn: Laurent Brochard, MD
- Telefonnummer: 5686 416-864-6060
- E-post: laurent.brochard@unityhealth.to
Studieorter
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Buenos Aires, Argentina
- Rekrytering
- Hospital Británico de Buenos Aires
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Kontakt:
- Gustavo Plotnikov, RRT
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Buenos Aires, Argentina
- Rekrytering
- Complejo Médico Policía Federal Argentina Churruca Visca
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Kontakt:
- Maria Guaymas, MD
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Buenos Aires, Argentina
- Rekrytering
- Sanatorio Anchorena Recoleta
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Kontakt:
- Daniela Vasquez, MD
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Buenos Aires, Argentina
- Rekrytering
- Sanatorio Mater Dei
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Kontakt:
- Magalí Gutiérrez, MD
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Buenos Aires, Argentina
- Rekrytering
- Centro de Educación Médica e Investigaciones Clínicas Dr Norberto Quirno (CEMIC)
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Kontakt:
- Pablo Rodriguez, MD
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San Martin, Argentina
- Rekrytering
- Sanatorio Anchorena San Martín
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Kontakt:
- Matias Accoce, RRT
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Santiago, Chile
- Rekrytering
- Pontificia Universidad Católica de Chile
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Kontakt:
- Felipe Damiani, PhD
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Amiens, Frankrike
- Rekrytering
- CHU Amiens-Picardie
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Kontakt:
- Michel Slama, MD
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Angers, Frankrike
- Rekrytering
- Centre hospitalier universitaire d'Angers
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Kontakt:
- Francois Beloncle, MD
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Argenteuil, Frankrike
- Rekrytering
- CH Victor Dupouy
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Kontakt:
- Gaetan Plantefeve, MD
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Beauvais, Frankrike
- Rekrytering
- CH de Beauvais
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Kontakt:
- Jack Richecoeur, MD
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Bordeaux, Frankrike
- Rekrytering
- CHU Bordeaux - Haut Leveque
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Kontakt:
- Benjamin Repusseau, MD
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Brest, Frankrike
- Rekrytering
- Hopital de la Cavale Blanche - CHRU Brest
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Kontakt:
- Gwenael Prat, MD
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Cholet, Frankrike
- Rekrytering
- CH de Cholet
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Kontakt:
- Johann Auchabie, MD
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Créteil, Frankrike
- Rekrytering
- Hopital Intercommunal de Creteil
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Kontakt:
- Tommaso Maraffi, MD
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Grenoble, Frankrike
- Rekrytering
- CHU Grenoble-Alpes
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Kontakt:
- Florian Sigaud, MD
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Lille, Frankrike
- Rekrytering
- Hopital Roger Salengro - CHU Lille
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Kontakt:
- Saad Nseir, MD
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Mulhouse, Frankrike
- Rekrytering
- Groupe Hospitalier de la Region de Mulhouse et Sud Alsace
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Kontakt:
- Khaldoun Kuteifan, MD
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Nice, Frankrike
- Rekrytering
- Hopital de l'Archet 1 - CHU de Nice
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Kontakt:
- Jean Dellamonica, MD
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Paris, Frankrike
- Rekrytering
- Hopital Europeen Georges-Pompidou
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Kontakt:
- Jean-Luc Diehl, MD
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Poitiers, Frankrike
- Rekrytering
- CHU de Poitiers - La Miletrie
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Kontakt:
- Remi Coudroy, MD
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Vannes, Frankrike
- Rekrytering
- CH Bretagne Atlantique Vannes-Auray
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Kontakt:
- Agathe Delbove, MD
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Villenave-d'Ornon, Frankrike
- Rekrytering
- HIA Robert Picque
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Kontakt:
- David Tran-Van, MD
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New York
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New York, New York, Förenta staterna, 10016
- Rekrytering
- New York University Grossman School of Medicine
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Kontakt:
- David Kaufman, MD
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Ferrara, Italien
- Rekrytering
- Arcispedale Sant'Anna
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Kontakt:
- Savino Spadaro, MD
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Foggia, Italien
- Rekrytering
- University of Foggia
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Kontakt:
- Michela Rauseo, MD
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Rome, Italien
- Rekrytering
- Policlinico Universitario Agostino Gemelli IRCCS
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Kontakt:
- Domenico L Grieco, MD
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Toronto, Kanada
- Rekrytering
- St. Michael's Hospital
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Kontakt:
- Laurent Brochard, MD
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Toronto, Kanada
- Rekrytering
- Toronto General Hospital
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Kontakt:
- Ewan Goligher, MD
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Toronto, Kanada
- Rekrytering
- Toronto Western Hospital
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Kontakt:
- Irene Telias, MD
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North Holland
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Amsterdam, North Holland, Nederländerna
- Rekrytering
- OLVG
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Kontakt:
- Rogier Determann, MD
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Barcelona, Spanien
- Rekrytering
- Vall d'Hebron University Hospital
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Kontakt:
- Andres F Pacheco, MD
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Barcelona, Spanien
- Rekrytering
- L'Hospital de la Santa Creu i Sant Pau
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Kontakt:
- Marta I Gomez, MD
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Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
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
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Enda
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Aktiv komparator: 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. |
|
Experimentell: 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. |
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
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All-cause 60-day mortality
Tidsram: 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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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
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Duration of ventilation
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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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Andra resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
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The change in biomarker expression
Tidsram: 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
|
Samarbetspartners och utredare
Sponsor
Samarbetspartners
Utredare
- Huvudutredare: Laurent Brochard, MD, Unity Health Toronto
Publikationer och användbara länkar
Allmänna publikationer
- 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.
Användbara länkar
Studieavstämningsdatum
Studera stora datum
Studiestart (Faktisk)
Primärt slutförande (Beräknad)
Avslutad studie (Beräknad)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Faktisk)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
- Patologiska processer
- Luftvägsinfektioner
- Infektioner
- RNA-virusinfektioner
- Virussjukdomar
- Luftvägssjukdomar
- Lungsjukdomar
- Andningsstörningar
- Lunginflammation, Viral
- Lunginflammation
- Coronavirusinfektioner
- Coronaviridae-infektioner
- Nidovirales infektioner
- Patologiska tillstånd, tecken och symtom
- Covid-19
- Andningsaspiration
- Cirkulations- och andningsfysiologiska fenomen
- Andning
- Andningsfysiologiska fenomen
- Respiratorisk Mekanik
Andra studie-ID-nummer
- 1765
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
IPD-planbeskrivning
The final anonymized trial dataset will be available on reasonable written request to the principal investigator one year after publication of the main manuscript.
Läkemedels- och apparatinformation, studiedokument
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