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Plattform for randomiserte adaptive kliniske studier ved kritisk sykdom (PRACTICAL)

19. oktober 2026 oppdatert av: University Health Network, Toronto

PRACTICAL is a randomized multifactorial adaptive platform trial for acute hypoxemic respiratory failure (AHRF). This platform trial will evaluate novel interventions for patients with AHRF across a range of severity states (i.e., not intubated, intubated with lower or higher respiratory system elastance, requiring extracorporeal life support) and across a range of investigational phases (i.e., preliminary mechanistic trials, full-scale clinical trials). AHRF is a common and life-threatening clinical syndrome affecting millions globally every year. Patients with AHRF are at high risk of death and long-term morbidity. Patients who require invasive mechanical ventilation are at risk of ventilator-induced lung injury and ventilator-induced diaphragm dysfunction. New treatments and treatment strategies are needed to improve outcomes for these very ill patients.

Utilizing advances in Bayesian adaptive trial design, the platform will facilitate efficient yet rigorous testing of new treatments for AHRF, with a particular focus on mechanical ventilation strategies and extracorporeal life support techniques as well as pharmacological agents and new medical devices.

The platform is designed to enable evaluation of novel interventions at a variety of stages of investigation, including pilot and feasibility trials, trials focused on mechanistic surrogate endpoints for preliminary clinical evaluation, and full-scale clinical trials assessing the impact of interventions on patient-centered outcomes.

A domain is defined as a set of interventions that are intended to act on specific mechanisms of injury using different variations of a common therapeutic strategy. A domain may also be a non-interventional study that addresses observational research questions by collecting specific data or outcomes that are not collected as part of other domains. Domains are intended to function independently of each other, allowing independent evaluation of multiple therapies and mechanistic pathways within the same patient.

Once feasibility is established, Bayesian adaptive statistical modelling will be used to evaluate treatment efficacy at regular interim adaptive analyses of the pre-specified outcomes for each intervention in each domain. These adaptive analyses will compute the posterior probabilities of superiority, futility, inferiority, or equivalence for pre-specified comparisons within domains. Each of these potential conclusions will be pre-defined prior to commencing the intervention trial. Decisions about trial results (e.g., concluding superiority or equivalence) will be based on pre-specified threshold values for posterior probability. The primary outcome of interest, the definitions for superiority, futility, etc. (i.e., the magnitude of treatment effect) and the threshold values of posterior probability required to reach conclusions for superiority, futility etc., will vary from intervention to intervention depending on the phase of investigation and the nature of the intervention being evaluated. All of these parameters will be pre-specified as part of the statistical design for each intervention trial.

In general, domains will be designed to evaluate treatment effect within four discrete clinical states: non-intubated patients, intubated patients with low respiratory system elastance (<2.5 cm H2O/(mL/kg)), intubated patients with high respiratory system elastance (≥2.5 cm H2O/(mL/kg)), and patients requiring extracorporeal life support. Where appropriate, the model will specify dynamic borrowing between states to maximize statistical information available for trial conclusions. In this perpetual trial design, different interventions may be added or dropped over time.

Where possible, the platform will be embedded within existing data collection repositories to enable greater efficiency in outcome ascertainment. Standardized systems for acquiring both physiological and biological measurements are embedded in the platform, to be acquired at sites with appropriate training, expertise, and facilities to collect those measurements.

Studieoversikt

Status

Rekruttering

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

EXPAND-ECLS domain: The EXPAND-ECLS pilot trial is a multi-center, randomized, open-label, feasibility trial, embedded as a domain within the PRACTICAL platform trial. The ULTIMATE arm of this domain will evaluate the effect of ultra-low intensity ventilation facilitated by CO2 removal through VV-ECMO versus best current conventional ventilation on all-cause hospital mortality among patients with early moderate-severe AHRF with high respiratory system elastance receiving potentially injurious mechanical ventilation. The PROACTIVE arm of this domain will evaluate the effect of ECMO-facilitated strategy of earlier awakening, extubation, and rehabilitation versus best current conventional ventilation on all-cause hospital mortality among patients with early moderate-severe AHRF with high respiratory system elastance receiving potentially injurious mechanical ventilation.

Invasive Mechanical Ventilation (IMV) Strategies domain: The IMV Strategies domain will evaluate multiple novel invasive ventilation strategies in comparison to conventional lung-protective ventilation in patients with acute hypoxemic respiratory failure (AHRF). Multiple approaches to mechanical ventilation are used, and the optimal approach is unknown. An efficient strategy to identify the best strategy is to compare multiple potential approaches simultaneously to determine more rapidly (a) which interventions are least effective (and should be dropped), and (b) which interventions result in the best outcomes for patients. In the current domain design, we will compare the current recommended ventilation strategy to two new approaches: a strategy that targets lung-inflating (driving) pressure instead of lung-inflating (tidal) volume, and a strategy that aims to maintain an optimal level of breathing effort to prevent diaphragm atrophy and injury while maintaining safe lung-inflating pressures.

CORT-E2 domain: The Corticosteroid Early and Extended (CORT-E2) Trial is a phase III, multicentre Bayesian randomized controlled trial (RCT), which includes two cohorts within the domain; one examining the role of early corticosteroids as compared to not extending in persisting AHRF due to COVID or non-COVID (Extended Cohort).

ESCAPE domain: Evaluating Subphenotypes in Immunocompromized Patients with ARF (ESCAPE) Domain is a prospective, multicentre observational cohort study, to identify subphenotypes across immunocompromised patients with acute hypoxemic respiratory failure (AHRF) using clinical characteristics and biomarkers. This study will prospectively collect biomarkers at the onset of AHRF which will allow us to characterize the underlying pathophysiology of AHRF with better precision.

WAVEFORM domain: The Clinical Implications of Potentially Injurious Patient-Ventilator Interactions (WAVEFORM domain) a prospective, multicentre observational cohort study, that aims at understanding the short- and long-term clinical consequences of longitudinal exposure to abnormal patient ventilation interactions in patients with AHRF, role of sedation as a mediator in this relationship. It aims at also exploring the heterogeneity of treatment effect of various mechanical ventilation strategies tested in the IMV based on the presence and burden of abnormal patient-ventilator interactions.

FLUDRO domain: The Fludrocortisone in Acute Hypoxemic Respiratory Failure with Airspace Disease (FLUDRO-1) domain is a phase II I trial. The trial aims to provide direct clinical evidence to resolve a critical long-standing question regarding the use of steroids in the treatment of AHRF with airspace disease.

FAST-3 domain: The Nebulized Furosemide for the Treatment of Pulmonary Inflammation in Patients with Respiratory Failure Secondary to Pulmonary Infection domain is a phase III trial. It aims to use nebulized furosemide as supportive therapy to improve Advanced Respiratory Support (ARS) free days up to day 28 in critically ill patients with AHRF.

IMV-ECLS domain: The Invasive Mechanical Ventilation Strategies in Venovenous-Extracorporeal Life Support (PRESSURE; Positive Pressure to Maintain Lung Recruitment during Extracorporeal Life Support for Acute Hypoxemic Respiratory failure) is a pilot and feasibility trial. It aims to identify which positive end-expiratory pressure (PEEP) strategies improve lung function in patients with AHRF supported by ECLS.

IMPROV domain: The Inspiratory Muscle Training in Patients Receiving Ongoing Mechanical Ventilation is a pilot and feasibility RCT. It is designed to establish the feasibility of a definitive RCT of inspiratory muscle training to accelerate recovery from AHRF.

Studietype

Intervensjonell

Registrering (Antatt)

6250

Fase

  • Ikke aktuelt

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

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Studiesteder

  • Australia
      • Westmead, Australia, 2145
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
      • Kingswood, New South Wales, Australia, 2747
      • Wollongong, New South Wales, Australia, 2500
    • Queensland
      • Chermside, Queensland, Australia, 4032
        • Rekruttering
        • The Prince Charles Hospital
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    • Southern Adelaide
      • Bedford Park, Southern Adelaide, Australia, 5042
        • Rekruttering
        • Flinders Medical Centre
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    • Sydney
      • Darlinghurst, Sydney, Australia, 2010
    • Victoria
      • Bendigo, Victoria, Australia, 3550
      • Frankston, Victoria, Australia, 3199
      • Geelong, Victoria, Australia, 3220
      • Heidelberg, Victoria, Australia, 3084
        • Rekruttering
        • The Austin Hospital
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  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 1N4
        • Rekruttering
        • University of Calgary
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      • Edmonton, Alberta, Canada, T6G 2X8
        • Rekruttering
        • University of Alberta/Edmonton University Hospital
        • Ta kontakt med:
        • Hovedetterforsker:
          • Sean Bagshaw
        • Hovedetterforsker:
          • Gurmeet Singh
    • British Columbia
      • Nanaimo, British Columbia, Canada, V9S 2B7
      • Surrey, British Columbia, Canada, V3V 1Z2
        • Rekruttering
        • Surrey Memorial Hospital
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      • Vancouver, British Columbia, Canada, V6Z 1Y6
        • Rekruttering
        • St. Paul's Hospital
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      • Victoria, British Columbia, Canada, V8R 1J8
        • Rekruttering
        • Royal Jubilee Hospital
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        • Ta kontakt med:
          • Gordon Wood
      • Victoria, British Columbia, Canada, V8R 1J8
    • Manitoba
      • Winnipeg, Manitoba, Canada, R2H 2A6
      • Winnipeg, Manitoba, Canada, R3J 3M7
        • Rekruttering
        • Grace Hospital
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      • Winnipeg, Manitoba, Canada, R3A 1R9
        • Rekruttering
        • Health Sciences Centre - Winnipeg
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        • Hovedetterforsker:
          • Gloria Grande
        • Hovedetterforsker:
          • Owen Mooney
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3S 0H6
        • Rekruttering
        • Nova Scotia Health Authority
        • Ta kontakt med:
          • Edmund Chong-How Tan
          • Telefonnummer: 902-473-3608
          • E-post: cetan@dal.ca
    • Ontario
      • Brampton, Ontario, Canada, L6R 3J7
        • Rekruttering
        • William Osler Health System
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      • Brantford, Ontario, Canada, N3R 1G9
        • Rekruttering
        • Brantford General Hospital
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      • Hamilton, Ontario, Canada, L8L 2X2
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        • Hamilton Health Sciences Centre - General
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      • Hamilton, Ontario, Canada, L8V 1C3
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        • Hamilton Health Sciences Centre - Juravinski
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      • Hamilton, Ontario, Canada, L8N 4A6
        • Rekruttering
        • St. Joseph's Hamilton
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      • Kingston, Ontario, Canada, K7L 2V7
        • Rekruttering
        • Kingston Health Sciences Centre
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        • Hovedetterforsker:
          • Dave Maslove
      • London, Ontario, Canada, N6A 5W9
        • Har ikke rekruttert ennå
        • London Health Sciences Centre - Victoria Hospital
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      • London, Ontario, Canada, N6A 5W9
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        • London Health Sciences Centre - University Hospital
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      • Markham, Ontario, Canada, L3P 7P3
      • North York, Ontario, Canada, M2K 1E1
        • Rekruttering
        • North York General Hospital
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      • Oakville, Ontario, Canada, L6M 0L8
      • Oshawa, Ontario, Canada, L1G 8A2
        • Rekruttering
        • Lakeridge Hospital
        • Ta kontakt med:
        • Ta kontakt med:
          • Karim Soliman
          • Telefonnummer: 33720 905-576-8711
          • E-post: ksoliman@lh.ca
      • Ottawa, Ontario, Canada, K1H 8L6
        • Rekruttering
        • The Ottawa Hospital
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      • Ottawa, Ontario, Canada, K1Y 4W7
        • Har ikke rekruttert ennå
        • Ottawa Heart Research Institute
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      • Richmond Hill, Ontario, Canada, L4C 4Z3
      • Saint Catherines, Ontario, Canada, L2S 0A9
      • Toronto, Ontario, Canada, M1P 2V5
        • Rekruttering
        • Scarborough Health Network
        • Ta kontakt med:
          • Christopher J Yarnell
          • Telefonnummer: 416-438-2911
          • E-post: cyarnell@shn.ca
      • Toronto, Ontario, Canada, M4N 3M5
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        • Sunnybrook Health Sciences Centre
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      • Toronto, Ontario, Canada, M5C 2T2
        • Rekruttering
        • Unity Health Toronto
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        • Hovedetterforsker:
          • Jan Friedrich
        • Hovedetterforsker:
          • Michael Sklar
      • Toronto, Ontario, Canada, M5G 1X5
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        • Sinai Health, Mount Sinai Hospital
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      • Toronto, Ontario, Canada
        • Rekruttering
        • University Health Network
        • Hovedetterforsker:
          • Niall Ferguson
        • Ta kontakt med:
        • Ta kontakt med:
        • Hovedetterforsker:
          • Lorenzo Del Sorbo
        • Hovedetterforsker:
          • Irene Telias
        • Hovedetterforsker:
          • Dmitry Rozenberg
        • Hovedetterforsker:
          • Laveena Munshi
      • Vaughan, Ontario, Canada, L6A 4Z3
      • Windsor, Ontario, Canada, N8W 1L9
    • Quebec
      • Laval, Quebec, Canada, H7M 3L9
      • Montreal, Quebec, Canada, H2X 0C1
        • Rekruttering
        • Centre hospitalier de l'Université de Montréal (CHUM)
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      • Montreal, Quebec, Canada, H4A 0B1
        • Rekruttering
        • MUHC - McGill University Health Centre (Glen Site)
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      • Montreal, Quebec, Canada, H4J 1C5
      • Sherbrooke, Quebec, Canada, J1J 3H5
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        • Centre Hospitalier Universite de Sherbrooke
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      • Trois-Rivières, Quebec, Canada, G8Z 3R9
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        • Trois Riviere (CHAUR)
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    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7N 0W8
        • Rekruttering
        • University of Saskatchewan
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  • Colombia
    • Cundinamarca
      • Chía, Cundinamarca, Colombia
        • Rekruttering
        • Clínica Universidad de La Sabana
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  • Forente stater
    • Arizona
      • Tucson, Arizona, Forente stater, 85724
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      • Los Angeles, California, Forente stater, 90095
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      • San Diego, California, Forente stater, 92121
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      • San Francisco, California, Forente stater, 94143
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    • Colorado
      • Aurora, Colorado, Forente stater, 80045
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    • Kentucky
      • Lexington, Kentucky, Forente stater, 40506
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    • Maryland
      • Baltimore, Maryland, Forente stater, 21201
      • Baltimore, Maryland, Forente stater, 21224
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        • The Johns Hopkins Medicine
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    • Michigan
      • Ann Arbor, Michigan, Forente stater, 48105
        • Rekruttering
        • VA Ann Arbor Healthcare System
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      • Ann Arbor, Michigan, Forente stater, 48109
        • Rekruttering
        • University of Michigan Health
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    • Missouri
      • St Louis, Missouri, Forente stater, 63130
        • Rekruttering
        • Washington University
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    • Nebraska
      • Omaha, Nebraska, Forente stater, 68198
        • Rekruttering
        • University of Nebraska Medical Center
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    • New York
      • New York, New York, Forente stater, 10032
        • Rekruttering
        • Columbia University Irving Medical Center
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      • New York, New York, Forente stater, 10029
        • Rekruttering
        • Mount Sinai New York City
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    • North Carolina
      • Winston-Salem, North Carolina, Forente stater, 27101
        • Rekruttering
        • Wake Forest University School of Medicine
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    • Ohio
      • Cincinnati, Ohio, Forente stater, 45267
        • Rekruttering
        • University of Cincinnati College of Medicine
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      • Cleveland, Ohio, Forente stater, 44195
        • Rekruttering
        • Cleveland Clinic
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    • Oregon
      • Portland, Oregon, Forente stater, 97239
        • Rekruttering
        • Oregon Health & Science University (OHSU)
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    • Pennsylvania
      • Philadelphia, Pennsylvania, Forente stater, 19104
      • Philadelphia, Pennsylvania, Forente stater, 19107
        • Rekruttering
        • Thomas Jefferson University Hospital
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      • Pittsburgh, Pennsylvania, Forente stater, 15213
        • Rekruttering
        • University of Pittsburgh Medical Center (UPMC)
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    • Rhode Island
      • Providence, Rhode Island, Forente stater, 02903
        • Rekruttering
        • Rhode Island Hospital
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    • South Carolina
      • Charleston, South Carolina, Forente stater, 29425
        • Rekruttering
        • Medical University of South Carolina (MUSC)
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    • Tennessee
      • Nashville, Tennessee, Forente stater, 37232
        • Rekruttering
        • Vanderbilt university medical center
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        • Ta kontakt med:
        • Underetterforsker:
          • Margaret Hayes
    • Texas
      • El Paso, Texas, Forente stater, 79905
    • Utah
      • Farmington, Utah, Forente stater, 84025
        • Rekruttering
        • University of Utah Health
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    • Virginia
      • Norfolk, Virginia, Forente stater, 23507
        • Rekruttering
        • Sentara Health
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  • Hong Kong
      • Hong Kong, Hong Kong
        • Rekruttering
        • Queen Mary Hospital
        • Ta kontakt med:
        • Ta kontakt med:
  • Italia
    • FG
      • Foggia, FG, Italia, 71122
        • Rekruttering
        • Policlinico Riuniti Foggia
        • Ta kontakt med:
    • Ferrara
      • Cona, Ferrara, Italia, 44124
        • Rekruttering
        • Azienda Ospedaliero-Universitaria di Ferrara
        • Ta kontakt med:
    • MI
      • Legnano, MI, Italia, 20025
    • Michigan
      • Milan, Michigan, Italia, 20122
        • Rekruttering
        • Ospedale Maggiore, Fondazione IRCCS Ca Granda, Milano
        • Ta kontakt med:
      • Milan, Michigan, Italia, 20162
        • Rekruttering
        • ASST Grande Ospedale Metropolitano Niguarda
        • Ta kontakt med:
    • PA
      • Palermo, PA, Italia, 90127
        • Rekruttering
        • Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
        • Ta kontakt med:
    • RM
      • Roma, RM, Italia, 00168
        • Rekruttering
        • Policlinico Universitario Agostino Gemelli
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    • SS
      • Sassari, SS, Italia, 07100
        • Rekruttering
        • Azienda Ospedaliero Universitaria - Sassari
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    • TN
      • Trento, TN, Italia, 38122
        • Rekruttering
        • Ospedale Santa Chiara di Trento
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  • New Zealand
      • Auckland, New Zealand, 2025
      • New Plymouth, New Zealand, 4310
      • Rotorua, New Zealand, 3010
    • Auckland
      • Grafton, Auckland, New Zealand, 1023
        • Rekruttering
        • Auckland City Hospital
        • Ta kontakt med:
    • New Zealand
  • Saudi-Arabia
      • Riyadh, Saudi-Arabia, 11426
        • Rekruttering
        • King Abdulaziz Medical City- Riyadh
        • Ta kontakt med:
  • Singapore
      • Singapore, Singapore, 119077
  • Spania
      • Girona, Spania, 17007
        • Rekruttering
        • Hospital Josep Trueta (Girona)
        • Ta kontakt med:
      • Santa Cruz de Tenerife, Spania, 38010
        • Rekruttering
        • Hospital U Virgen de la Candelaria
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    • Barcelona
      • Ciutat Vella, Barcelona, Spania, 08003
        • Rekruttering
        • Hospital del Mar
        • Ta kontakt med:
          • Francisco José Parrilla-Gomez
          • Telefonnummer: +34 932 48 30 00
          • E-post: fparrilla@hmar.cat
      • Horta-Guinardó, Barcelona, Spania, 08035
      • L'Hospitalet de Llobregat, Barcelona, Spania, 08907
      • Sabadell, Barcelona, Spania, 08208
        • Aktiv, ikke rekrutterende
        • Parc Taulí University Hospital

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

PRACTICAL Platform Inclusion Criteria:

  1. Acute hypoxemic respiratory failure meeting all of the following criteria;

    1. New or worsening respiratory symptoms developing within 2 weeks prior to the onset of need for oxygen or respiratory support
    2. Receiving any of the following types of oxygen or respiratory support for at least 4 hours prior to the time of randomization; supplemental oxygen at 10 L/min or higher, high flow nasal oxygen (at any flow rate), invasive ventilator support, extra-corporeal life support (ECLS), or non-invasive ventilator support
    3. Minimum FiO2 ≥ 0.40 (for venturi mask, high flow nasal cannula, or invasive or non-invasive ventilation) or oxygen flow rate ≥10 L/min on face mask for at least 4 hours at the time of evaluation for eligibility unless already on extra-corporeal life support

  2. Age ≥ 18 years

  3. Hypoxemia not primarily attributable to acute heart failure, fluid overload, or pulmonary embolism (PE)

PRACTICAL Platform Exclusion Criteria:

  1. Extubation is planned or anticipated on the day of screening
  2. ICU discharged is planned or anticipated on the day of screening
  3. If the patient is moribund and deemed unlikely to survive 24 hours (as determined by the clinical team)
  4. If the patient is being transitioned to a fully palliative philosophy of care

EXPAND-ECLS Domain Inclusion Criteria:

  1. Receiving invasive Endotracheal mechanical ventilation for ≤ 72 hours.5 days
  2. Early Moderate-severe hypoxemic respiratory failure with a PaO2/FiO2≤150200 mmHg for at least 6 hours

EXPAND-ECLS Domain Exclusion Criteria:

  1. Patients over 70 years of age.
  2. Currently receiving any form of ECLS (e.g., Venovenous, venoarterial, or hybrid configuration).
  3. Chronic hypercapnic respiratory failure defined as PaCO2 > 60 mmHg in the outpatient setting.
  4. Home mechanical ventilation (non-invasive ventilation or via tracheotomy) except for CPAP/BiPAP used solely for sleep-disordered breathing.
  5. Actual body weight exceeding 1 kg per centimeter of height.
  6. More than 48 hours have passed since meeting inclusion criteria.
  7. Severe hypoxemia with PaO2/FiO2 < 80mmHg for > 6 hours at time of screening.
  8. Severe hypercapnic respiratory failure with pH < 7.25 and PaCO2 > 60 mmHg for > 6 hours at time of screening.
  9. Expected mechanical ventilation duration < 48 hours at time of screening.
  10. Confirmed diffuse alveolar hemorrhage from vasculitis.
  11. Contraindications to limited anticoagulation (e.g., active GI bleeding, bleeding diathesis).
  12. Previous hypersensitivity/anaphylactic reaction to heparin or heparin-induced thrombocytopenia
  13. Neurologic conditions at risk for or undergoing treatment for intracranial hypertension
  14. Underlying illness with life expectancy < 1 year
  15. Pregnancy (due to unknown effects of PaCO2 changes on placental blood flow)
  16. Respiratory failure known or suspected to be caused by COVID-19.

IMV Domain Inclusion Criteria:

  1. Intubated patients, not on ECLS, with low normalized respiratory elastance (<2.5 cm H2O/(ml/kg predicted body weight)) at the time of eligibility assessment OR
  2. Intubated patients, not on ECLS, with high normalized respiratory system elastance (≥2.5 cm H2O/(ml/kg predicted body weight)) at the time of eligibility assessment OR
  3. FOR STUDY SITES PARTICIPATING IN THE LDPVS INTERVENTION: Patient is on ECLS at the time of eligibility assessment. Note: Patients in this state are only eligible for the LPV or LDPVS intervention
  4. FOR STUDY SITES PARTICPATING IN THE EIT INTERVENTION: PaO2/FiO2 (if available) < 200 mm Hg at randomization. If PaO2/FiO2 has not been measured, SpO2 = 97% on FiO2 =60%.

IMV Domain Exclusion Criteria:

  1. PaO2/FiO2 >300 mm Hg or (S/F >250, if PaO2/FiO2 has not been measured) at the time of randomization
  2. Chronic hypercapnic respiratory failure defined as PaCO2>60mmHg in the outpatient setting
  3. Home mechanical ventilation (non-invasive ventilation or via tracheotomy), not including nocturnal CPAP applied by nasal or face mask or home tracheotomy if not ventilated
  4. Severe hypoxemia with PaO2/FiO2<80mmHg for >6 consecutive hours at the time of randomization
  5. Severe hypercapnic respiratory failure with pH<7.25 and PaCO2>60mmHg for >6 consecutive hours at the time of randomization
  6. Anticipated duration of mechanical ventilation is <48 hours from the time of screening
  7. Duration of mechanical ventilation during current ICU admission is >72 hours
  8. Previously diagnosed neuromuscular disorder
  9. Current diagnosis of severe acute brain injury (e.g. ischemic or hemorrhagic stroke, traumatic brain injury) with Glasgow Coma Scale ≤ 8
  10. Baseline weight prior to or at hospital admission less than 35 kilograms
  11. Receiving extracorporeal life support without continuous invasive mechanical ventilatory support

CORT-E2 Domain Early Cohort Inclusion Criteria

  1. Within 72 hours of admission to an ICU
  2. New unilateral or bilateral airspace disease

CORT-E2 Domain Early Domain Exclusion Criteria

  1. Receiving only low flow oxygen therapy less than or equal to 15L/min
  2. Corticosteroid use during the 14 days prior to screening
  3. Existing indication for corticosteroids
  4. High suspicion for/or confirmed COVID infection
  5. Acute traumatic brain injury during the index hospital admission
  6. Allergy to dexamethasone

CORT-E2 Domain Extended Cohort Inclusion Criteria

  1. Are admitted to an ICU
  2. Have already received 10 days of corticosteroid specifically for acute respiratory failure, this will include patients: (a) randomized to corticosteroid arm in Early Cohort, (b) patients with COVID receiving corticosteroids as standard of care , (c) and others who have received corticosteroids for AHRF
  3. Ongoing AHRF requiring HFNC, NIV (continuous positive airway pressure [CPAP] or bilevel) or invasive ventilation

CORT-E2 Domain Extended Cohort Exclusion Criteria

  1. An alternate indication for ongoing corticosteroids
  2. Acute traumatic brain injury this hospital admission

FLUDRO Domain Inclusion Criteria 1. Within 72 hours of admission to an ICU

FLUDRO Domain Exclusion Criteria

  1. Known hypersensitivity to fludrocortisone
  2. An inability to receive fludrocortisone due to lack of enteral access
  3. An indication to prescribe fludrocortisone for a reason that is unrelated to a current episode of pneumonia or acute respiratory failure, such as Addison's disease
  4. Belief of the treating clinical team that study participation would not be in the best interest of the patient

FAST-3 Domain Inclusion Criteria (must meet all 3 of the following)

  1. Patient is in a PRACTICAL eligible platform state and requires advanced respiratory support (ARS) defined as one of the following:

    a. Invasive mechanical ventilation with FiO2 > 40% b. Non-Invasive Ventilation (> 4 hours consecutively with FiO2 > 40%) defined as: i. CPAP or BiPAP (any settings or interface) ii. HFNC (flow > 40 liter per minute)

  2. PaO2/FiO2 < 300 mm Hg or SpO2/FiO2 < 315 (if PaO2/FiO2 unavailable due to lack of arterial blood gas at the time of screening). For SpO2/FiO2, criteria are SpO2 ≤ 97% on FiO2 ≥ 40% on both of the 2 hours immediately preceding eligibility assessment. If an arterial blood gas can be obtained, then a PaO2/FiO2 ratio is preferable.

  3. Patient commenced advanced respiratory support < 48 hours prior to randomization.

FAST-3 Domain Exclusion Criteria

  1. Patient commenced advanced respiratory support > 48 hours to time of randomization.
  2. Known history of severe chronic pulmonary disease e.g., pre-infection requirement for home oxygen therapy or presence of chronic hypercapnia (PaCO2 > 60 mmHg); mild - moderate disease is still eligible in the absence of chronic hypercapnia or need for chronic oxygen therapy.
  3. Currently enrolled in another trial studying investigational anti-inflammatory therapy, excluding established treatments used in clinical practice such as corticosteroids.
  4. Known allergy to furosemide or sulfonamide drugs. If the patient is allergic to sulfonamide drugs but has received in the past or is currently receiving furosemide without incident, they can be enrolled since cross-reactivity between furosemide and sulfonamide agents is rare.

ESCAPE Domain Inclusion Criteria

  1. Patients with severe AHRF who have an underlying immunocompromised condition
  2. Within 48 hours of fulfilling the AHRF inclusion criteria as well as PaO2/FiO2 <300 or a SaO2/FiO2 < 315 on non-invasive respiratory support (venturi mask, non-invasive ventilation or high flow nasal oxygen as per the FiO2 requirements above) or invasive ventilation.

Patients may be enrolled from the wards or ICU.

Immunocompromised patients include:

  1. Any patients requiring long term (>30 days) corticosteroids (>20 mg/day),

  2. Any patients receiving non-corticosteroid immunosuppressive medications within the prior 3 months,

  3. Acquired or inherited immunodeficiency syndrome,

  4. Recipients of solid organ transplant,

  5. Active hematologic malignancy (diagnosis or receiving treatment within prior 6 months),

  6. Active solid tumor (diagnosis or receiving treatment within the prior 6 months) or

  7. Any patients who have undergone allogeneic or autologous hematopoietic cell transplant in the prior 6 months (HCT).

    ESCAPE Domain Exclusion Criteria

    1. Patients whom are deemed palliative.

    WAVEFORM Domain Inclusion Criteria

    1. Patient is intubated at the time of eligibility assessment.

    WAVEFORM Domain Exclusion Criteria

    1. PaO2/FiO2 >300 mm Hg or (S/F >250, if PaO2/FiO2 has not been measured) at the time of eligibility assessment.
    2. Duration of mechanical ventilation during current ICU admission is ≥72 hours.
    3. Receiving ECLS without continuous invasive mechanical ventilatory support.

    IMV-ECLS Domain Inclusion Criteria

    1. Patients with AHRF (as defined in platform inclusion criteria #1 above) who have been consented for cannulation for VV-ECLS or who have been initiated on VV-ECLS within 6 hours at the time of randomization

    IMV-ECLS Domain Exclusion Criteria 1. Patients receiving ECLS for the primary intention of extracorporeal CO2 removal 2. Patients expected to be liberated from ECLS within <24 hours 3. History of recent pneumothorax or pneumomediastinum (<3 months at the time of eligibility assessment/randomization) 4. Patients receiving ECLS for the primary intention of bridge to lung transplantation (at the time of eligibility assessment/randomization)

    IMPROV Domain Inclusion Criteria

    1. Patients receiving invasive mechanical ventilation for AHRF as defined by the PRACTICAL platform trial criteria above.
    2. Within 7 calendar days of intubation

    IMPROV Domain Exclusion Criteria

    1. Patient is expected to be liberated from mechanical ventilation within 24 hours
    2. Known or suspected chronic hypercapnic respiratory failure defined as PaCO2>60mmHg in the outpatient setting
    3. Home mechanical ventilation (non-invasive ventilation or via tracheotomy), not including nocturnal CPAP applied by nasal or face mask or home tracheotomy if not ventilated
    4. Known pneumothorax or pneumomediastinum without chest tube placement sustained during current ICU admission* (re-confirm immediately prior to randomization)
    5. Patient is admitted primarily for acute brain injury (stroke, traumatic brain injury, etc.)
    6. Previously diagnosed chronic neuromuscular disorder
    7. Patient has an implantable cardiac defibrillator or pacemaker
    8. Planned to be transferred to another hospital before ICU discharge
    9. Already receiving a regimen of inspiratory muscle training using external resistive device or diaphragm neurostimulation

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Dobbelt

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Annen: Ultra-protective ventilation facilitated by extracorporeal carbon dioxide removal.

Patients randomized to the this intervention group will receive VV-ECMO with the ventilator set to minimize driving pressure and respiratory rate for ultra-protective ventilation.
Annen: Ultra-Protective Ventilation Facilitated by Extracorporeal Support

Patients randomized to this intervention group will receive VV-ECMO with the ventilator set to minimize driving pressure and respiratory rate for ultra-protective ventilation.

Annen: Lung-Protective Ventilation (LPV)

Patients randomized to LPV will receive standard of care lung-protective ventilation with conventional limits on tidal volume and plateau airway pressure.

Annen: VV ECMO-facilitated strategy of earlier awakening, extubation and rehabilitation

Patients randomized to this intervention group will receive VV-ECMO where the sedation will be reduced and the ventilator will will be adjusted to facilitate spontaneous breathing.
Annen: Invasive Mechanical Ventilation (IMV) Strategies domain

Patients on invasive mechanical ventilation in the low elastance, high elastance, and ECLS states will be randomized to minimum of one of two mechanical ventilation interventions (including conventional lung-protective ventilation as a control group). Most sites will randomize patients to two arms (one of which is the control group, LPV). A subset of sites will randomize patients to all three or four arms.
Annen: Lung-Protective Ventilation (LPV)

Patients randomized to LPV will receive standard of care lung-protective ventilation with conventional limits on tidal volume and plateau airway pressure.

Annen: Driving Pressure-Limited Ventilation (DPL)

Patients randomized to DPL will receive mechanical ventilation set to maintain a safe limit on driving pressure and plateau airway pressure, without less for the tidal volume.

Annen: Lung- and Diaphragm-Protective Ventilation and Sedation (LDPVS)

Patients randomized to LDPVS will have ventilation and sedation adjusted to maintain lung-distending pressure and respiratory effort in a safe target range.

Annen: Electrical impedance tomography (EIT)

Patients randomized to EIT will have PEEP titration compared via the Overdistension Collapse Intercept (ODCL) versus that obtained using a standard high PEEP table.
Annen: The Corticosteroid Early and Extended (CORT-E2) Randomized Controlled Trial domain

Patients with acute hypoxemic respiratory failure (AHRF) requiring invasive or non-invasive respiratory support will be randomized in the Early Cohort to receive corticosteroid or usual care without corticosteroids. Patients treated with corticosteroids who still require invasive or non-invasive respiratory support after 10 days will be randomized in the Extended Cohort to extending corticosteroid use or stopping corticosteroids after 10 days.
Legemiddel: Early Cohort corticosteroid dose

Patients randomized to receive corticosteroids will receive dexamethasone 20mg daily for 5 days and then 10mg for an additional 5 days, for a total of 10 days from the time of randomization (or until ICU discharge or death, whichever comes first); after 10 days dexamethasone will be stopped without a taper.

Legemiddel: Extended Cohort corticosteroid dose

Patients randomized to receive extended corticosteroids will receive dexamethasone 10mg for an additional 10 days. At the end of the additional 10 days (day 20 of corticosteroids), the dexamethasone dose will be halved to 5mg for another 5 days (to reduce the risk of adrenal insufficiency) and then stopped (a total of 25 days or until ICU discharge or death, whichever comes first).

Legemiddel: Usual care without routine corticosteroids

Patients randomized to this arm will be managed according to usual care. They will receive corticosteroids only if prescribed by the clinician.

Legemiddel: Usual care without extending corticosteroids

Corticosteroids will stop after 10 days. Other management will be according to usual care. Patients will receive corticosteroids only if prescribed by the clinician.
Annen: The Nebulized Furosemide for the Treatment of Pulmonary Inflammation (FAST-3) domain

Patients with Respiratory Failure Secondary to Pulmonary Infection.
Legemiddel: Drug 4 mL:

4 mL of nebulized 0.9% saline minutes every 6 hours over 30 minutes every 6 hours.

Legemiddel: Drug 40 mg:

40 mg of nebulized furosemide in 4 mL of saline nebulized over 30 minutes every 6 hours
Annen: The Invasive Mechanical Ventilation Strategies in Venovenous-Extracorporeal Life Support (IMV-ECLS)

Patients with acute hypoxemic respiratory failure receiving extracorporeal life support will be randomized to one of three positive end-expiratory pressure (PEEP) strategies.
Annen: PEEP-20

fixed high positive end-expiratory pressure at 20 cmH2O

Annen: PEEP-AOP

positive end-expiratory pressure set according to airway opening pressure

Annen: PEEP-10

fixed lower positive end-expiratory pressure at 10 cmH2O
Annen: The Fludrocortisone in Acute Hypoxemic Respiratory Failure with Airspace Disease (FLUDRO-1) domain

Patients with acute hypoxemic respiratory failure with airspace disease will be randomized to usual care with or without fludrocortisone.
Legemiddel: Usual care with fludrocortisone

Best practice standard of care prescribed by treating team + fludrocortisone 50μg enterally daily for 7 days.

Legemiddel: Usual care without fludrocortisone

Best practice standard of care prescribed by treating team without fludrocortisone. After randomization, if a clinical indication develops for fludrocortisone as part of standard of care, administration of fludrocortisone is not prohibited. Any fludrocortisone administered to participants in the control arm will be documented.
Annen: VV ECMO-facilitated strategy of earlier awakening, extubation and rehabilitation

Patients with acute hypoxemic respiratory failure in the high elastance state will be randomized to ultra-protective ventilation facilitated by extracorporeal carbon dioxide removal or to VV ECMO-facilitated strategy of earlier awakening, extubation and rehabilitation or to conventional lung-protective ventilation.
Annen: Ultra-Protective Ventilation Facilitated by Extracorporeal Support

Patients randomized to this intervention group will receive VV-ECMO with the ventilator set to minimize driving pressure and respiratory rate for ultra-protective ventilation.

Annen: Lung-Protective Ventilation (LPV)

Patients randomized to LPV will receive standard of care lung-protective ventilation with conventional limits on tidal volume and plateau airway pressure.

Annen: VV ECMO-facilitated strategy of earlier awakening, extubation and rehabilitation

Patients randomized to this intervention group will receive VV-ECMO where the sedation will be reduced and the ventilator will will be adjusted to facilitate spontaneous breathing.
Annen: Evaluating Subphenotypes in Immunocompromized Patients with ARF (ESCAPE) Domain

We will conduct a prospective, multicenter, observational study (no treatment arm is involved) in 7 ICUs in Canada over 3 years. We will include adult patients (≥18 years) admitted to the ICU with AHRF who have an underlying immunocompromised condition.

Biomarker Collection: Samples for serum biomarkers will be collected within 24 hours of fulfilling inclusion criteria, on days 0, 3 and 7. We will collect biomarkers associated with inflammatory conditions, epithelial injury, endothelial dysfunction and coagulation abnormalities - which have been shown to characterize lung injury or critical illness.

Data Collection: We will collect demographic, comorbidity, immunocompromised defining condition, clinical, respiratory physiology, and serum biomarker data for each patient.
Annen: no treatment / intervention arm is involved

This trial is a prospective, multicenter, observational study (no treatment arm is involved).
Annen: Inspiratory Muscle Training in Patients Receiving Ongoing Mechanical Ventilation (IMPROV) Domain

This domain studies inspiratory muscle training (IMT) during and after mechanical ventilation in patients with acute hypoxemic respiratory failure (AHRF).
Annen: Usual care

Patients will be treated according to usual care.

Annen: Early Routine IMT
  • Training commences once patients meet readiness to wean criteria
  • 3 sets of 10 breaths, delivered twice daily using a device placed at the airway opening to apply an external resistive pressure load, until hospital discharge, death, or day 45 after randomization, whichever occurs first.
  • Device load will initially be set to 30% of the MIP.
  • Device load will be titrated upward (in increments of 5-10% of MIP, to a maximum of 60% of MIP) as needed to achieve a modified Borg dyspnea score of 7/10 or visible accessory muscle use.
Annen: Clinical Implications of Potentially Injurious Patient-Ventilator Interactions (WAVEFORM) Domain

This domain primarily aims at understanding the short-and long-term clinical consequences of longitudinal exposure to abnormal patient ventilator interactions.
Annen: no treatment / intervention arm is involved.

This trial is a prospective, multicenter, observational study (no treatment arm is involved).

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
CORT-E2-domene - 60-dagers dødelighet fra randomiseringsdagen
Tidsramme: Dag 60
Dag 60
ESKAPERING-domene - 28-dagers mortalitet fra alle årsaker
Tidsramme: 28-dagers
28-dagers
EXPAND-ECLS domain - determine the feasibility of recruiting 100 patients over 2 years of active enrolment, as well as assess the rate of participant recruitment and understand the barriers to enrollment.
Tidsramme: 2 years of active site enrollment.

Record total number of patients randomized, total number of patients eligible yet not randomized, and the number of active randomizing sites on a monthly basis. This will include evaluating the validity and appropriateness of inclusion and exclusion criteria, trial acceptability, and reasons for lack of consent or withdrawal.
2 years of active site enrollment.
FLUDRO-1 and IMV domains - ventilator-free days to day 28 in DPL vs LPV (DRIVE RCT)
Tidsramme: Day 28 post randomization

Ventilator-free days to day 28 is computed as an ordinal scale ranging between -1 to 28. Patients who die in hospital will be assigned a value of -1. Otherwise the endpoint will be computed from the number of days alive and free of ventilation in the period between the day the patient is liberated from mechanical ventilation and day 28.
Day 28 post randomization
IMV domain - adherence to LDPVS management (LANDMARK RCT)
Tidsramme: Day 28

Adherence to LDPVS management will be measured in terms of the proportion of protocol-specified measurements of respiratory effort that are on target during the intervention period.
Day 28
IMV domain - probability of achieving and maintaining lung- and diaphragm-protective targets during mechanical ventilation (LANDMARK RCT)
Tidsramme: Day 28

Lung- and diaphragm-protective targets are defined as an estimated dynamic trans pulmonary driving pressure ≤23 cm H2O and a Pocc value between -6 to -20 cm H2O.
Day 28
IMV domain - protocol adherence (EIT intervention)
Tidsramme: Day 9

Protocol adherence will be measured as a binary outcome daily, while patients are receiving EIT. The target protocol adherence across patients is ≥80%.
Day 9
FLUDRO-1 domain - Successful enrollment of participants
Tidsramme: 18-month enrolment period across three platform trials (PRACTICAL, REMAP-CAP and ATTACC-CAP)

Protocol adherence: e.g., proportion of participants randomized to fludrocortisone who received the study drug as specified in the protocol; Consent rate; Early withdrawal from domain intervention; Outcome completeness
18-month enrolment period across three platform trials (PRACTICAL, REMAP-CAP and ATTACC-CAP)
FAST-3 domain - Advanced respiratory support free days
Tidsramme: Day 28

Advanced respiratory support free days (ARSFDs) to day 28, a composite outcome including mortality and requirement for respiratory support
Day 28
IMV-ECLS domain - feasibility of enrollment and protocol adherence
Tidsramme: For feasibility of enrollment: 2 years of active site enrollment; For protocol adherence, these will be evaluated at 7 days (once the intervention period ends)

Feasibility of enrollment defined as ≥1 patient enrolled per month per site. Protocol adherence defined as ≥90% of patients initiated on assigned PEEP strategy within 6 hours of ECLS cannulation and ≥90% average protocol adherence across participants.
For feasibility of enrollment: 2 years of active site enrollment; For protocol adherence, these will be evaluated at 7 days (once the intervention period ends)
IMPROV domain - recruitment rate, protocol adherence, and vital status
Tidsramme: Throughout trial enrollment for recruitment rate and protocol adherence, and up to day 90 for vital status.

≥0.75 patients randomized per site per month, Protocol adherence defined as > 80% across participants, and ≥89% ascertainment of vital status and days alive and at home at day 90.
Throughout trial enrollment for recruitment rate and protocol adherence, and up to day 90 for vital status.
WAVEFORM domain
Tidsramme: considering death as a competing event

Duration of mechanical ventilation (MV)
considering death as a competing event

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
To assess adherence to our explicit mechanical ventilation protocols.
Tidsramme: 48 hours

Adherence to protocol defined as >80% of patients having <20% of monitored values determined to be major protocol deviations.
48 hours
To measure and understand the reasons for crossovers in each group
Tidsramme: 2 years

Success for lack of crossovers defined as <10% of crossovers between groups (when not allowed by protocol) in either direction.
2 years
Duration of mechanical ventilation during index ICU admission
Tidsramme: Until ICU discharge, typically within 28 days

Measured in CORT-E2, IMV, IMV-ECLS and EXPAND-ECLS domains
Until ICU discharge, typically within 28 days
Mortality at other endpoints
Tidsramme: ICU discharge, hospital discharge, day 30, 180 for CORT E2, IMV, IMV ECLS, and EXPAND ECLS.For ESCAPE:hospital mortality @ 60 days and 6 months.For FAST 3:all cause mortality @ 60 days post enrollment.For IMPROV:day 90.For WAVEFORM:day 28 after inclusion

Measured in CORT-E2, ESCAPE, FAST-3, IMV, IMV-ECLS, IMPROV and EXPAND-ECLS and WAVEFORM domains
ICU discharge, hospital discharge, day 30, 180 for CORT E2, IMV, IMV ECLS, and EXPAND ECLS.For ESCAPE:hospital mortality @ 60 days and 6 months.For FAST 3:all cause mortality @ 60 days post enrollment.For IMPROV:day 90.For WAVEFORM:day 28 after inclusion
Vital status
Tidsramme: Day 90 and at 6 months

Measured in IMPROV domain
Day 90 and at 6 months
Duration of ICU admission
Tidsramme: Until ICU discharge, typically within 28 days

Measured in FAST-3, IMV, IMV-ECLS and EXPAND-ECLS and WAVEFORM domains
Until ICU discharge, typically within 28 days
Hospital length of stay
Tidsramme: Until hospital discharge, assessed up to 4 weeks

Measured in CORT-E2, FAST-3, IMV, IMV-ECLS and WAVEFORM domains
Until hospital discharge, assessed up to 4 weeks
ICU and hospital free days
Tidsramme: For FAST-3: ICU discharge, hospital discharge, Day 28. For IMPROV: Day 90.

Measured in FAST-3, IMPROV domains
For FAST-3: ICU discharge, hospital discharge, Day 28. For IMPROV: Day 90.
Discharge disposition.
Tidsramme: Until hospital discharge, assessed up to 4 weeks

Measured in IMV, IMV-ECLS, IMPROV domains. Location to which patient is discharged (e.g., home, weaning facility, etc.)
Until hospital discharge, assessed up to 4 weeks
Days alive and at home to day 90
Tidsramme: Day 90

Measured in IMV, IMV-ECLS and FLUDRO-1 and WAVEFORM domains
Day 90
Need for ICU readmission prior to hospital discharge
Tidsramme: Until hospital discharge, assessed up to 4 weeks

Measured in IMV, IMV-ECLS domains
Until hospital discharge, assessed up to 4 weeks
Duration of NIV
Tidsramme: Until ICU discharge, typically within 28 days

Measured in CORT-E2 domain
Until ICU discharge, typically within 28 days
Duration of supplemental oxygen use
Tidsramme: Until ICU discharge, typically within 28 days

Measured in CORT-E2 domain
Until ICU discharge, typically within 28 days
Need for ECLS
Tidsramme: Until ICU discharge, typically within 28 days

Measured in CORT-E2 domain
Until ICU discharge, typically within 28 days
Duration of ECLS, only for patients who require ECLS
Tidsramme: Until ICU discharge, typically within 28 days

Measured in CORT-E2, IMV-ECLS domains.
Until ICU discharge, typically within 28 days
Ventilator-free days until day 30 for CORT-E2; until day 28 for FAST-3, FLUDRO-1, ULTIMATE and WAVEFORM( ordinal scale composed of survival to hospital discharge, days alive and free of ventilation where death in the hospital is assigned a score of -1).
Tidsramme: Until day 30 for CORT-E2, and until day 28 for FAST-3, FLUDRO-1, ULTIMATE and WAVEFORM

Measured in CORT-E2, FAST-3, FLUDRO-1, ULTIMATE and WAVEFORM domains.
Until day 30 for CORT-E2, and until day 28 for FAST-3, FLUDRO-1, ULTIMATE and WAVEFORM
EQ-5-D at day 180
Tidsramme: For CORT-E2, FAST-3, IMV, and IMV-ECLS domains: Day 180; For IMPROV domain: Day 90 and Day 180.

Measured in CORT-E2, FAST-3, IMV, IMV-ECLS, IMPROV, WAVEFORM domains
For CORT-E2, FAST-3, IMV, and IMV-ECLS domains: Day 180; For IMPROV domain: Day 90 and Day 180.
Montreal Cognitive Assessment (MoCA) At day 180
Tidsramme: Day 180

Measured in FAST-3 domain
Day 180
Complications from corticosteroids.
Tidsramme: Until hospital discharge, assessed up to 4 weeks

Measured in CORT-E2 domain. Hypernatremia, hyperglycemia, delirium, clinically important GI bleeding, nosocomial infection, neuromuscular weakness.

Measured in FLUDRO-1 domain: Hypernatremia, Hyperglycemia, Hypokalemia, Clinically important gastrointestinal bleeding, New nosocomial infection
Until hospital discharge, assessed up to 4 weeks
Reintubation during index ICU admission
Tidsramme: Until ICU discharge, typically within 28 days

Measured in IMV, IMV-ECLS domains
Until ICU discharge, typically within 28 days
Number of reintubations up to tracheostomy during index hospitalization
Tidsramme: Until hospital discharge

Measured in IMPROV domain
Until hospital discharge
Tracheostomy during index ICU admission
Tidsramme: Until ICU discharge, typically within 28 days

Measured in IMV, IMV-ECLS, IMPROV domains
Until ICU discharge, typically within 28 days
Re-cannulation to ECLS during index ICU admission
Tidsramme: Until ICU discharge, typically within 28 days

Measured in IMV-ECLS domain
Until ICU discharge, typically within 28 days
Sequential Organ Failure Assessment (SOFA) score
Tidsramme: Daily, for duration of intervention

Measured in IMV, IMV-ECLS domains
Daily, for duration of intervention
Respiratory mechanics and gas exchange - Driving pressure.
Tidsramme: Daily, for duration of intervention

Measured in IMV, IMV-ECLS domains.
Daily, for duration of intervention
Respiratory mechanics and gas exchange - Pocc.
Tidsramme: Daily, for duration of intervention

Measured in IMV, IMV-ECLS domains.
Daily, for duration of intervention
Respiratory mechanics and gas exchange - P0.1
Tidsramme: Daily, for duration of intervention

Measured in IMV, IMV-ECLS domains.
Daily, for duration of intervention
Respiratory mechanics and gas exchange - plateau airway pressure
Tidsramme: Daily, for duration of intervention

Measured in IMV, IMV-ECLS domains.
Daily, for duration of intervention
Respiratory mechanics and gas exchange - P/F ratio
Tidsramme: Daily, for duration of intervention

Measured in IMV, IMV-ECLS domains.
Daily, for duration of intervention
Respiratory mechanics and gas exchange - ventilatory ratio
Tidsramme: Daily, for duration of intervention

Measured in IMV domain.
Daily, for duration of intervention
Diaphragm thickness
Tidsramme: Daily, for duration of intervention

Measured in IMV domain
Daily, for duration of intervention
Maximal diaphragm thickening fraction
Tidsramme: During first SBT

Measured in IMV domain
During first SBT
Survival status at disconnection from mechanical ventilation (dead or alive)
Tidsramme: Until day 28

Measured in EXPAND-ECLS domain
Until day 28
Organ failure-free days
Tidsramme: Until day 28

Measured in ESCAPE, FLUDRO-1 domains
Until day 28
Serious adverse events (SAEs)
Tidsramme: Throughout the trial

Serious adverse events (SAEs) related to the intervention measured in FAST-3 domain
Throughout the trial
Modified Lung Injury Score (mLIS)
Tidsramme: Until day 10

Measured in IMV-EIT intervention. Calculated daily up until study day 10 in patients who are alive and continue to have acute hypoxemic respiratory failure requiring invasive mechanical ventilation.
Until day 10
Number of days from first SBT to disconnection from mechanical ventilation
Tidsramme: Until ICU discharge

Measured in IMPROV domain - final date of extubation or the first day of continuous tracheostomy mask for at least 24 hours, provided ventilator support is not resumed during the index ICU admission.
Until ICU discharge
Barotrauma during hospital admission
Tidsramme: Until 45 days or hospital discharge

Measured in IMPROV domain including pneumothorax, pneumomediastinum, subcutaneous emphysema
Until 45 days or hospital discharge
Cardiac arrest during hospital admission
Tidsramme: Until 45 days or hospital discharge

Measured in IMPROV domain
Until 45 days or hospital discharge
30 second sit to stand test at ICU discharge and hospital discharge
Tidsramme: Until ICU discharge, typically within 28 days

Measured in IMPROV domain
Until ICU discharge, typically within 28 days
Modified Medical Research Council (mMRC) Dyspnea Scale
Tidsramme: At ICU discharge, Day 90, Day 180

Measured in IMPROV domain
At ICU discharge, Day 90, Day 180
Physical function (Activity Measure for Post-Acute Care)
Tidsramme: At ICU discharge, Day 90, Day 180

Measured in IMPROV domain
At ICU discharge, Day 90, Day 180
Days alive at day 180 after inclusion
Tidsramme: Day 180

Measured in WAVEFORM domains
Day 180
Incidence of abnormal PVIs in each ventilation strategy
Tidsramme: 7 days

Measured in WAVEFORM domain
7 days
Sedation and NMBA use, type, simultaneous and cumulative dose
Tidsramme: 7 days, 28 days

Measured in WAVEFORM domain
7 days, 28 days
Vasopressor use, type, simultaneous and cumulative dose
Tidsramme: 7 days, 28 days

Measured in WAVEFORM domain
7 days, 28 days
PTSD symptoms (IES-R)
Tidsramme: Day 180

Measured in WAVEFORM domain
Day 180
Cognitive status (MoCA-BLIND)
Tidsramme: Day 180

Measured in WAVEFORM domain
Day 180

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

University Health Network, Toronto

Etterforskere

  • Studiestol: Ewan Goligher, MD, PhD, University Health Network, Toronto
  • Studiestol: Eddy Fan, MD, PhD, University Health Network, Toronto
  • Hovedetterforsker: Niall Ferguson, MD, MSc, University Health Network, Toronto
  • Hovedetterforsker: John Muscedere, MD, Queens University
  • Hovedetterforsker: Lorenzo Del Sorbo, MD, University Health Network, Toronto
  • Hovedetterforsker: Bram Rochwerg, MD, MSc, McMaster University
  • Hovedetterforsker: Laurent Brochard, MD, Unity Health Toronto
  • Hovedetterforsker: Bijan Teja, MD, Unity Health Toronto
  • Hovedetterforsker: Laveena Munshi, MD, Mount Sinai Hospital, Canada
  • Hovedetterforsker: Dmitry Rozenberg, MD, PhD, University Health Network, Toronto
  • Hovedetterforsker: Anastasia Newman, PhD, McMaster University
  • Hovedetterforsker: Irene Telias, MD, PhD, University Health Network, Toronto
  • Hovedetterforsker: Andrea Castellvi Font, MD, PhD, Parc de Salut Mar, Spain

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

30. april 2023

Primær fullføring (Antatt)

31. mars 2027

Studiet fullført (Antatt)

31. mars 2027

Datoer for studieregistrering

Først innsendt

10. november 2021

Først innsendt som oppfylte QC-kriteriene

27. juni 2022

Først lagt ut (Faktiske)

1. juli 2022

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

22. oktober 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

19. oktober 2026

Sist bekreftet

1. desember 2025

Mer informasjon

Begreper knyttet til denne studien

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • 21-5940

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

produkt produsert i og eksportert fra USA

Nei

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