Forsiktig ventilasjon ved akutt respiratorisk distress-syndrom (COVID-19 og ikke-COVID-19) (CAVIARDS)
Forsiktig ventilasjon ved akutt respiratorisk distress-syndrom
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.).
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
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.
Studietype
Registrering (Antatt)
Fase
- Ikke aktuelt
Kontakter og plasseringer
Studiekontakt
- Navn: Laurent Brochard, MD
- Telefonnummer: 5686 416-864-6060
- E-post: laurent.brochard@unityhealth.to
Studiesteder
-
-
-
Buenos Aires, Argentina
- Rekruttering
- Hospital Británico de Buenos Aires
-
Ta kontakt med:
- Gustavo Plotnikov, RRT
-
Buenos Aires, Argentina
- Rekruttering
- Complejo Médico Policía Federal Argentina Churruca Visca
-
Ta kontakt med:
- Maria Guaymas, MD
-
Buenos Aires, Argentina
- Rekruttering
- Sanatorio Anchorena Recoleta
-
Ta kontakt med:
- Daniela Vasquez, MD
-
Buenos Aires, Argentina
- Rekruttering
- Sanatorio Mater Dei
-
Ta kontakt med:
- Magalí Gutiérrez, MD
-
Buenos Aires, Argentina
- Rekruttering
- Centro de Educación Médica e Investigaciones Clínicas Dr Norberto Quirno (CEMIC)
-
Ta kontakt med:
- Pablo Rodriguez, MD
-
San Martin, Argentina
- Rekruttering
- Sanatorio Anchorena San Martín
-
Ta kontakt med:
- Matias Accoce, RRT
-
-
-
-
-
Toronto, Canada
- Rekruttering
- St. Michael's Hospital
-
Ta kontakt med:
- Laurent Brochard, MD
-
Toronto, Canada
- Rekruttering
- Toronto General Hospital
-
Ta kontakt med:
- Ewan Goligher, MD
-
Toronto, Canada
- Rekruttering
- Toronto Western Hospital
-
Ta kontakt med:
- Irene Telias, MD
-
-
-
-
-
Santiago, Chile
- Rekruttering
- Pontificia Universidad Católica de Chile
-
Ta kontakt med:
- Felipe Damiani, PhD
-
-
-
-
New York
-
New York, New York, Forente stater, 10016
- Rekruttering
- New York University Grossman School of Medicine
-
Ta kontakt med:
- David Kaufman, MD
-
-
-
-
-
Amiens, Frankrike
- Rekruttering
- CHU Amiens-Picardie
-
Ta kontakt med:
- Michel Slama, MD
-
Angers, Frankrike
- Rekruttering
- Centre hospitalier universitaire d'Angers
-
Ta kontakt med:
- Francois Beloncle, MD
-
Argenteuil, Frankrike
- Rekruttering
- CH Victor Dupouy
-
Ta kontakt med:
- Gaetan Plantefeve, MD
-
Beauvais, Frankrike
- Rekruttering
- CH de Beauvais
-
Ta kontakt med:
- Jack Richecoeur, MD
-
Bordeaux, Frankrike
- Rekruttering
- CHU Bordeaux - Haut Leveque
-
Ta kontakt med:
- Benjamin Repusseau, MD
-
Brest, Frankrike
- Rekruttering
- Hopital de la Cavale Blanche - CHRU Brest
-
Ta kontakt med:
- Gwenael Prat, MD
-
Cholet, Frankrike
- Rekruttering
- CH de Cholet
-
Ta kontakt med:
- Johann Auchabie, MD
-
Créteil, Frankrike
- Rekruttering
- Hopital Intercommunal de Creteil
-
Ta kontakt med:
- Tommaso Maraffi, MD
-
Grenoble, Frankrike
- Rekruttering
- CHU Grenoble-Alpes
-
Ta kontakt med:
- Florian Sigaud, MD
-
Lille, Frankrike
- Rekruttering
- Hopital Roger Salengro - CHU Lille
-
Ta kontakt med:
- Saad Nseir, MD
-
Mulhouse, Frankrike
- Rekruttering
- Groupe Hospitalier de la Region de Mulhouse et Sud Alsace
-
Ta kontakt med:
- Khaldoun Kuteifan, MD
-
Nice, Frankrike
- Rekruttering
- Hopital de l'Archet 1 - CHU de Nice
-
Ta kontakt med:
- Jean Dellamonica, MD
-
Paris, Frankrike
- Rekruttering
- Hopital Europeen Georges-Pompidou
-
Ta kontakt med:
- Jean-Luc Diehl, MD
-
Poitiers, Frankrike
- Rekruttering
- CHU de Poitiers - La Miletrie
-
Ta kontakt med:
- Remi Coudroy, MD
-
Vannes, Frankrike
- Rekruttering
- CH Bretagne Atlantique Vannes-Auray
-
Ta kontakt med:
- Agathe Delbove, MD
-
Villenave-d'Ornon, Frankrike
- Rekruttering
- HIA Robert Picque
-
Ta kontakt med:
- David Tran-Van, MD
-
-
-
-
-
Ferrara, Italia
- Rekruttering
- Arcispedale Sant'Anna
-
Ta kontakt med:
- Savino Spadaro, MD
-
Foggia, Italia
- Rekruttering
- University of Foggia
-
Ta kontakt med:
- Michela Rauseo, MD
-
Rome, Italia
- Rekruttering
- Policlinico Universitario Agostino Gemelli IRCCS
-
Ta kontakt med:
- Domenico L Grieco, MD
-
-
-
-
North Holland
-
Amsterdam, North Holland, Nederland
- Rekruttering
- OLVG
-
Ta kontakt med:
- Rogier Determann, MD
-
-
-
-
-
Barcelona, Spania
- Rekruttering
- Vall d'Hebron University Hospital
-
Ta kontakt med:
- Andres F Pacheco, MD
-
Barcelona, Spania
- Rekruttering
- L'Hospital de la Santa Creu i Sant Pau
-
Ta kontakt med:
- Marta I Gomez, MD
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Enkelt
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / 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. |
|
Eksperimentell: 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. |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
All-cause 60-day mortality
Tidsramme: 60 days
|
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
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Duration of ventilation
Tidsramme: May exceed 60 days
|
Duration of ventilation in days |
May exceed 60 days
|
|
Duration of ICU and hospital stay
Tidsramme: May exceed 60 days
|
Duration of ICU and hospital stay in days |
May exceed 60 days
|
|
Number of patients with organ dysfunction
Tidsramme: Day 1-7, 14, 21, 28
|
Organ dysfunction as per the SOFA score |
Day 1-7, 14, 21, 28
|
|
Number of patients with barotrauma
Tidsramme: Up to 60 days
|
Barotrauma defined as new onset of pneumothorax |
Up to 60 days
|
|
Mortality at ICU discharge, 28 days, and hospital discharge
Tidsramme: Up to date of ICU discharge, 28 days, and hospital discharge
|
Mortality |
Up to date of ICU discharge, 28 days, and hospital discharge
|
Andre resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
The change in biomarker expression
Tidsramme: Baseline, 24 and 72 hours
|
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
|
Samarbeidspartnere og etterforskere
Sponsor
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: Laurent Brochard, MD, Unity Health Toronto
Publikasjoner og nyttige lenker
Generelle publikasjoner
- 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.
Hjelpsomme linker
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Patologiske prosesser
- Luftveisinfeksjoner
- Infeksjoner
- RNA-virusinfeksjoner
- Virussykdommer
- Sykdommer i luftveiene
- Lungesykdommer
- Respirasjonsforstyrrelser
- Lungebetennelse, viral
- Lungebetennelse
- Coronavirus-infeksjoner
- Coronaviridae-infeksjoner
- Nidovirales infeksjoner
- Patologiske tilstander, tegn og symptomer
- Covid-19
- Respirasjonsaspirasjon
- Sirkulasjons- og luftveisfysiologiske fenomener
- Respirasjon
- Luftveisfysiologiske fenomener
- Respiratorisk mekanikk
Andre studie-ID-numre
- 1765
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
IPD-planbeskrivelse
The final anonymized trial dataset will be available on reasonable written request to the principal investigator one year after publication of the main manuscript.
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Studerer et amerikansk FDA-regulert enhetsprodukt
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .