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Omhyggelig ventilation ved akut respiratorisk distress-syndrom (COVID-19 og ikke-COVID-19) (CAVIARDS)

5. november 2026 opdateret af: Unity Health Toronto

Omhyggelig ventilation ved akut 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.).

Studieoversigt

Status

Rekruttering

Betingelser

Intervention / Behandling

Detaljeret 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.

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

740

Fase

  • Ikke anvendelig

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Studiesteder

      • Buenos Aires, Argentina
        • Rekruttering
        • Hospital Británico de Buenos Aires
        • Kontakt:
          • Gustavo Plotnikov, RRT
      • Buenos Aires, Argentina
        • Rekruttering
        • Complejo Médico Policía Federal Argentina Churruca Visca
        • Kontakt:
          • Maria Guaymas, MD
      • Buenos Aires, Argentina
        • Rekruttering
        • Sanatorio Anchorena Recoleta
        • Kontakt:
          • Daniela Vasquez, MD
      • Buenos Aires, Argentina
        • Rekruttering
        • Sanatorio Mater Dei
        • Kontakt:
          • Magalí Gutiérrez, MD
      • Buenos Aires, Argentina
        • Rekruttering
        • Centro de Educación Médica e Investigaciones Clínicas Dr Norberto Quirno (CEMIC)
        • Kontakt:
          • Pablo Rodriguez, MD
      • San Martin, Argentina
        • Rekruttering
        • Sanatorio Anchorena San Martín
        • Kontakt:
          • Matias Accoce, RRT
      • Toronto, Canada
        • Rekruttering
        • St. Michael's Hospital
        • Kontakt:
          • Laurent Brochard, MD
      • Toronto, Canada
        • Rekruttering
        • Toronto General Hospital
        • Kontakt:
          • Ewan Goligher, MD
      • Toronto, Canada
        • Rekruttering
        • Toronto Western Hospital
        • Kontakt:
          • Irene Telias, MD
      • Santiago, Chile
        • Rekruttering
        • Pontificia Universidad Católica de Chile
        • Kontakt:
          • Felipe Damiani, PhD
    • New York
      • New York, New York, Forenede Stater, 10016
        • Rekruttering
        • New York University Grossman School of Medicine
        • Kontakt:
          • David Kaufman, MD
      • Amiens, Frankrig
        • Rekruttering
        • CHU Amiens-Picardie
        • Kontakt:
          • Michel Slama, MD
      • Angers, Frankrig
        • Rekruttering
        • Centre hospitalier universitaire d'Angers
        • Kontakt:
          • Francois Beloncle, MD
      • Argenteuil, Frankrig
        • Rekruttering
        • CH Victor Dupouy
        • Kontakt:
          • Gaetan Plantefeve, MD
      • Beauvais, Frankrig
        • Rekruttering
        • CH de Beauvais
        • Kontakt:
          • Jack Richecoeur, MD
      • Bordeaux, Frankrig
        • Rekruttering
        • CHU Bordeaux - Haut Leveque
        • Kontakt:
          • Benjamin Repusseau, MD
      • Brest, Frankrig
        • Rekruttering
        • Hopital de la Cavale Blanche - CHRU Brest
        • Kontakt:
          • Gwenael Prat, MD
      • Cholet, Frankrig
        • Rekruttering
        • CH de Cholet
        • Kontakt:
          • Johann Auchabie, MD
      • Créteil, Frankrig
        • Rekruttering
        • Hopital Intercommunal de Creteil
        • Kontakt:
          • Tommaso Maraffi, MD
      • Grenoble, Frankrig
        • Rekruttering
        • CHU Grenoble-Alpes
        • Kontakt:
          • Florian Sigaud, MD
      • Lille, Frankrig
        • Rekruttering
        • Hopital Roger Salengro - CHU Lille
        • Kontakt:
          • Saad Nseir, MD
      • Mulhouse, Frankrig
        • Rekruttering
        • Groupe Hospitalier de la Region de Mulhouse et Sud Alsace
        • Kontakt:
          • Khaldoun Kuteifan, MD
      • Nice, Frankrig
        • Rekruttering
        • Hopital de l'Archet 1 - CHU de Nice
        • Kontakt:
          • Jean Dellamonica, MD
      • Paris, Frankrig
        • Rekruttering
        • Hopital Europeen Georges-Pompidou
        • Kontakt:
          • Jean-Luc Diehl, MD
      • Poitiers, Frankrig
        • Rekruttering
        • CHU de Poitiers - La Miletrie
        • Kontakt:
          • Remi Coudroy, MD
      • Vannes, Frankrig
        • Rekruttering
        • CH Bretagne Atlantique Vannes-Auray
        • Kontakt:
          • Agathe Delbove, MD
      • Villenave-d'Ornon, Frankrig
        • Rekruttering
        • HIA Robert Picque
        • Kontakt:
          • David Tran-Van, MD
    • North Holland
      • Amsterdam, North Holland, Holland
        • Rekruttering
        • OLVG
        • Kontakt:
          • Rogier Determann, MD
      • Ferrara, Italien
        • Rekruttering
        • Arcispedale Sant'Anna
        • Kontakt:
          • Savino Spadaro, MD
      • Foggia, Italien
        • Rekruttering
        • University of Foggia
        • Kontakt:
          • Michela Rauseo, MD
      • Rome, Italien
        • Rekruttering
        • Policlinico Universitario Agostino Gemelli IRCCS
        • Kontakt:
          • Domenico L Grieco, MD
      • Barcelona, Spanien
        • Rekruttering
        • Vall d'Hebron University Hospital
        • Kontakt:
          • Andres F Pacheco, MD
      • Barcelona, Spanien
        • Rekruttering
        • L'Hospital de la Santa Creu i Sant Pau
        • Kontakt:
          • Marta I Gomez, MD

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Enkelt

Våben og indgreb

Deltagergruppe / 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.

Eksperimentel: 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.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
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
Foranstaltningsbeskrivelse
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
Foranstaltningsbeskrivelse
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

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Samarbejdspartnere

Efterforskere

  • Ledende efterforsker: Laurent Brochard, MD, Unity Health Toronto

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Hjælpsomme links

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

23. november 2020

Primær færdiggørelse (Anslået)

1. juni 2027

Studieafslutning (Anslået)

1. september 2027

Datoer for studieregistrering

Først indsendt

6. maj 2019

Først indsendt, der opfyldte QC-kriterier

23. maj 2019

Først opslået (Faktiske)

24. maj 2019

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

10. november 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

5. november 2026

Sidst verificeret

1. januar 2026

Mere information

Begreber relateret til denne undersøgelse

Andre undersøgelses-id-numre

  • 1765

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

JA

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.

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

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Ingen

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

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