Platform of Randomized Adaptive Clinical Trials in Critical Illness (PRACTICAL)

May 1, 2026 updated by: 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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

6250

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
      • Kingswood, New South Wales, Australia, 2747
      • Wollongong, New South Wales, Australia, 2500
    • Southern Adelaide
      • Bedford Park, Southern Adelaide, Australia, 5042
    • Sydney
      • Darlinghurst, Sydney, Australia, 2010
        • Recruiting
        • St Vincents Sydney
    • Victoria
      • Bendigo, Victoria, Australia, 3550
        • Recruiting
        • Bendigo Health Victoria
      • Geelong, Victoria, Australia, 3220
      • Heidelberg, Victoria, Australia, 3084
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 1N4
        • Recruiting
        • University Of Calgary
        • Contact:
      • Edmonton, Alberta, Canada, T6G 2X8
        • Recruiting
        • University of Alberta/Edmonton University Hospital
        • Contact:
        • Principal Investigator:
          • Sean Bagshaw
        • Principal Investigator:
          • Gurmeet Singh
    • British Columbia
      • Nanaimo, British Columbia, Canada, V9S 2B7
        • Recruiting
        • Nanaimo Regional General Hospital
      • Surrey, British Columbia, Canada, V3V 1Z2
        • Recruiting
        • Surrey Memorial Hospital
        • Contact:
      • Vancouver, British Columbia, Canada, V6Z 1Y6
        • Recruiting
        • St. Paul's Hospital
        • Contact:
      • Victoria, British Columbia, Canada, V8R 1J8
        • Recruiting
        • Royal Jubilee Hospital
      • Victoria, British Columbia, Canada, V8R 1J8
    • Manitoba
      • Winnipeg, Manitoba, Canada, R2H 2A6
      • Winnipeg, Manitoba, Canada, R3J 3M7
        • Recruiting
        • Grace Hospital
        • Contact:
      • Winnipeg, Manitoba, Canada, R3A 1R9
        • Recruiting
        • Health Sciences Centre - Winnipeg
        • Contact:
        • Principal Investigator:
          • Gloria Grande
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3S 0H6
        • Recruiting
        • Nova Scotia Health Authority
        • Contact:
          • Edmund Chong-How Tan
          • Phone Number: 902-473-3608
          • Email: cetan@dal.ca
    • Ontario
      • Brampton, Ontario, Canada, L6R 3J7
      • Brantford, Ontario, Canada, N3R 1G9
        • Recruiting
        • Brantford General Hospital
        • Contact:
      • Hamilton, Ontario, Canada, L8L 2X2
        • Recruiting
        • Hamilton Health Sciences Centre - General
        • Contact:
      • Hamilton, Ontario, Canada, L8V 1C3
        • Recruiting
        • Hamilton Health Sciences Centre - Juravinski
        • Contact:
      • Hamilton, Ontario, Canada, L8N 4A6
        • Recruiting
        • St. Joseph's Hamilton
        • Contact:
      • Kingston, Ontario, Canada, K7L 2V7
        • Recruiting
        • Kingston Health Sciences Centre
        • Contact:
        • Principal Investigator:
          • Dave Maslove
      • London, Ontario, Canada, N6A 5W9
        • Not yet recruiting
        • London Health Sciences Centre - Victoria Hospital
        • Contact:
      • London, Ontario, Canada, N6A 5W9
        • Not yet recruiting
        • London Health Sciences Centre - University Hospital
        • Contact:
      • Markham, Ontario, Canada, L3P 7P3
      • North York, Ontario, Canada, M2K 1E1
        • Recruiting
        • North York General Hospital
        • Contact:
      • Oakville, Ontario, Canada, L6M 0L8
      • Oshawa, Ontario, Canada, L1G 8A2
        • Recruiting
        • Lakeridge Hospital
        • Contact:
        • Contact:
          • Karim Soliman
          • Phone Number: 33720 905-576-8711
          • Email: ksoliman@lh.ca
      • Ottawa, Ontario, Canada, K1H 8L6
        • Recruiting
        • The Ottawa Hospital
        • Contact:
      • Ottawa, Ontario, Canada, K1Y 4W7
        • Not yet recruiting
        • Ottawa Heart Research Institute
        • Contact:
      • Richmond Hill, Ontario, Canada, L4C 4Z3
      • Saint Catherines, Ontario, Canada, L2S 0A9
      • Toronto, Ontario, Canada, M4N 3M5
      • Toronto, Ontario, Canada
        • Recruiting
        • University Health Network
        • Principal Investigator:
          • Niall Ferguson
        • Contact:
        • Contact:
        • Principal Investigator:
          • Lorenzo Del Sorbo
        • Principal Investigator:
          • Irene Telias
        • Principal Investigator:
          • Dmitry Rozenberg
      • Toronto, Ontario, Canada, M1P 2V5
        • Recruiting
        • Scarborough Health Network
        • Contact:
      • Toronto, Ontario, Canada, M5C 2T2
        • Recruiting
        • Unity Health Toronto
        • Contact:
        • Principal Investigator:
          • Jan Friedrich
        • Principal Investigator:
          • Michael Sklar
      • Toronto, Ontario, Canada, M5G 1X5
      • Vaughan, Ontario, Canada, L6A 4Z3
      • Windsor, Ontario, Canada, N8W 1L9
    • Quebec
      • Laval, Quebec, Canada, H7M 3L9
      • Montreal, Quebec, Canada, H2X 0C1
        • Recruiting
        • Centre Hospitalier de l'Universite de Montreal (CHUM)
        • Contact:
      • Montreal, Quebec, Canada, H4A 0B1
        • Recruiting
        • MUHC - McGill University Health Centre (Glen Site)
        • Contact:
      • Montreal, Quebec, Canada, H4J 1C5
      • Sherbrooke, Quebec, Canada, J1J 3H5
      • Trois-Rivières, Quebec, Canada, G8Z 3R9
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7N 0W8
        • Recruiting
        • University of Saskatchewan
        • Contact:
  • Colombia
    • Cundinamarca
      • Chía, Cundinamarca, Colombia
      • Chía, Cundinamarca, Colombia
  • Italy
    • MI
      • Legnano, MI, Italy, 20025
        • Recruiting
        • Azienda Socio-Sanitaria Territoriale Ovest Milanese
      • Milan, MI, Italy, 20162
        • Recruiting
        • Asst Grande Ospedale Metropolitano Niguarda
      • Milan, MI, Italy, 20122
        • Recruiting
        • Ospedale Maggiore, Fondazione IRCCS Ca Granda, Milano
  • New Zealand
      • Auckland, New Zealand, 2025
        • Recruiting
        • Middlemore Hospital
      • New Plymouth, New Zealand, 4310
        • Recruiting
        • Taranaki Base Hospital
      • Rotorua, New Zealand, 3010
        • Recruiting
        • Rotorua Hospital
    • Auckland
      • Grafton, Auckland, New Zealand, 1023
        • Recruiting
        • Auckland City Hospital
  • Saudi Arabia
      • Riyadh, Saudi Arabia, 11426
        • Recruiting
        • King Abdulaziz Medical City- Riyadh
  • Singapore
      • Singapore, Singapore, 119077
        • Recruiting
        • National University of Singapore
  • Spain
      • Girona, Spain, 17007
        • Recruiting
        • Hospital Josep Trueta (Girona)
    • Barcelona
      • Sabadell, Barcelona, Spain, 08208
        • Active, not recruiting
        • Parc Taulí University Hospital
    • Madrid
      • Getafe, Madrid, Spain, 28905
        • Not yet recruiting
        • Hospital Universitario de Getafe
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85724
    • California
      • Los Angeles, California, United States, 90095
        • Recruiting
        • University of California Los Angeles (UCLA)
        • Contact:
      • San Diego, California, United States, 92121
        • Recruiting
        • University of San Diego (UCSD)
        • Contact:
      • San Francisco, California, United States, 94143
        • Recruiting
        • University of California San Francisco
        • Contact:
    • Colorado
      • Aurora, Colorado, United States, 80045
    • Kentucky
      • Lexington, Kentucky, United States, 40506
        • Recruiting
        • University Of Kentucky
        • Contact:
    • Maryland
      • Baltimore, Maryland, United States, 21201
      • Baltimore, Maryland, United States, 21224
        • Recruiting
        • The Johns Hopkins Medicine
        • Contact:
    • Michigan
      • Ann Arbor, Michigan, United States, 48105
        • Not yet recruiting
        • VA Ann Arbor Healthcare System
        • Contact:
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan Health
        • Contact:
    • Missouri
      • St Louis, Missouri, United States, 63130
        • Recruiting
        • Washington University
        • Contact:
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • Recruiting
        • University of Nebraska Medical Center
        • Contact:
    • New York
      • New York, New York, United States, 10032
      • New York, New York, United States, 10029
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27101
    • Ohio
      • Cincinnati, Ohio, United States, 45267
        • Recruiting
        • University of Cincinnati College of Medicine
        • Contact:
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic
        • Contact:
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Oregon Health & Science University (OHSU)
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
      • Philadelphia, Pennsylvania, United States, 19107
      • Pittsburgh, Pennsylvania, United States, 15213
        • Recruiting
        • University of Pittsburgh Medical Center (UPMC)
        • Contact:
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Recruiting
        • Rhode Island Hospital
        • Contact:
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Recruiting
        • Medical University of South Carolina (MUSC)
        • Contact:
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt University Medical Center
        • Contact:
    • Utah
      • Farmington, Utah, United States, 84025
    • Virginia
      • Norfolk, Virginia, United States, 23507
        • Recruiting
        • Sentara Health
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: 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.
Drug: 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.
Drug: 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).
Drug: 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.
Drug: 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.
Other: The Nebulized Furosemide for the Treatment of Pulmonary Inflammation (FAST-3) domain
Patients with Respiratory Failure Secondary to Pulmonary Infection.
Drug: Drug 4 mL:
4 mL of nebulized 0.9% saline minutes every 6 hours over 30 minutes every 6 hours.
Drug: Drug 40 mg:
40 mg of nebulized furosemide in 4 mL of saline nebulized over 30 minutes every 6 hours
Other: 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.
Other: PEEP-20
fixed high positive end-expiratory pressure at 20 cmH2O
Other: PEEP-AOP
positive end-expiratory pressure set according to airway opening pressure
Other: PEEP-10
fixed lower positive end-expiratory pressure at 10 cmH2O
Other: 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.
Drug: Usual care with fludrocortisone
Best practice standard of care prescribed by treating team + fludrocortisone 50μg enterally daily for 7 days.
Drug: 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.
Other: 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.
Other: 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.
Other: 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.
Other: 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.
Other: 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.
Other: 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.
Other: 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.
Other: 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.
Other: 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.
Other: 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.
Other: 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.
Other: 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.
Other: 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.
Other: 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.
Other: no treatment / intervention arm is involved
This trial is a prospective, multicenter, observational study (no treatment arm is involved).
Other: 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).
Other: Usual care
Patients will be treated according to usual care.
Other: 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.
Other: 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.
Other: no treatment / intervention arm is involved.
This trial is a prospective, multicenter, observational study (no treatment arm is involved).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
IMV domain - adherence to LDPVS management (LANDMARK RCT)
Time Frame: 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)
Time Frame: 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
CORT-E2 domain - 60-day mortality from the day of randomization
Time Frame: Day 60
Day 60
FLUDRO-1 and IMV domains - ventilator-free days to day 28 in DPL vs LPV (DRIVE RCT)
Time Frame: 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
FLUDRO-1 domain - Successful enrollment of participants
Time Frame: 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
Time Frame: 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
Time Frame: 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)
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.
Time Frame: 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.
IMV domain - protocol adherence (EIT intervention)
Time Frame: 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
ESCAPE domain - 28-day all-cause mortality
Time Frame: 28-day
28-day
IMPROV domain - recruitment rate, protocol adherence, and vital status
Time Frame: 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
Time Frame: considering death as a competing event
Duration of mechanical ventilation (MV)
considering death as a competing event

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of NIV
Time Frame: Until ICU discharge, typically within 28 days
Measured in CORT-E2 domain
Until ICU discharge, typically within 28 days
Duration of supplemental oxygen use
Time Frame: Until ICU discharge, typically within 28 days
Measured in CORT-E2 domain
Until ICU discharge, typically within 28 days
Need for ECLS
Time Frame: Until ICU discharge, typically within 28 days
Measured in CORT-E2 domain
Until ICU discharge, typically within 28 days
Respiratory mechanics and gas exchange - ventilatory ratio
Time Frame: Daily, for duration of intervention
Measured in IMV domain.
Daily, for duration of intervention
Diaphragm thickness
Time Frame: Daily, for duration of intervention
Measured in IMV domain
Daily, for duration of intervention
Maximal diaphragm thickening fraction
Time Frame: During first SBT
Measured in IMV domain
During first SBT
Need for ICU readmission prior to hospital discharge
Time Frame: Until hospital discharge, assessed up to 4 weeks
Measured in IMV, IMV-ECLS domains
Until hospital discharge, assessed up to 4 weeks
Duration of ECLS, only for patients who require ECLS
Time Frame: Until ICU discharge, typically within 28 days
Measured in CORT-E2, IMV-ECLS domains.
Until ICU discharge, typically within 28 days
Montreal Cognitive Assessment (MoCA) At day 180
Time Frame: Day 180
Measured in FAST-3 domain
Day 180
Complications from corticosteroids.
Time Frame: 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
Time Frame: Until ICU discharge, typically within 28 days
Measured in IMV, IMV-ECLS domains
Until ICU discharge, typically within 28 days
Re-cannulation to ECLS during index ICU admission
Time Frame: 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
Time Frame: Daily, for duration of intervention
Measured in IMV, IMV-ECLS domains
Daily, for duration of intervention
Respiratory mechanics and gas exchange - Driving pressure.
Time Frame: Daily, for duration of intervention
Measured in IMV, IMV-ECLS domains.
Daily, for duration of intervention
Respiratory mechanics and gas exchange - Pocc.
Time Frame: Daily, for duration of intervention
Measured in IMV, IMV-ECLS domains.
Daily, for duration of intervention
Respiratory mechanics and gas exchange - P0.1
Time Frame: Daily, for duration of intervention
Measured in IMV, IMV-ECLS domains.
Daily, for duration of intervention
Respiratory mechanics and gas exchange - plateau airway pressure
Time Frame: Daily, for duration of intervention
Measured in IMV, IMV-ECLS domains.
Daily, for duration of intervention
Respiratory mechanics and gas exchange - P/F ratio
Time Frame: Daily, for duration of intervention
Measured in IMV, IMV-ECLS domains.
Daily, for duration of intervention
Serious adverse events (SAEs)
Time Frame: Throughout the trial
Serious adverse events (SAEs) related to the intervention measured in FAST-3 domain
Throughout the trial
To assess adherence to our explicit mechanical ventilation protocols.
Time Frame: 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
Time Frame: 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
Time Frame: 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
Survival status at disconnection from mechanical ventilation (dead or alive)
Time Frame: Until day 28
Measured in EXPAND-ECLS domain
Until day 28
Modified Lung Injury Score (mLIS)
Time Frame: 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
Vital status
Time Frame: Day 90 and at 6 months
Measured in IMPROV domain
Day 90 and at 6 months
ICU and hospital free days
Time Frame: 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.
Time Frame: 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
Number of reintubations up to tracheostomy during index hospitalization
Time Frame: Until hospital discharge
Measured in IMPROV domain
Until hospital discharge
Tracheostomy during index ICU admission
Time Frame: Until ICU discharge, typically within 28 days
Measured in IMV, IMV-ECLS, IMPROV domains
Until ICU discharge, typically within 28 days
Organ failure-free days
Time Frame: Until day 28
Measured in ESCAPE, FLUDRO-1 domains
Until day 28
Number of days from first SBT to disconnection from mechanical ventilation
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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)
Time Frame: At ICU discharge, Day 90, Day 180
Measured in IMPROV domain
At ICU discharge, Day 90, Day 180
Mortality at other endpoints
Time Frame: 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
Duration of ICU admission
Time Frame: 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
Time Frame: 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
Days alive and at home to day 90
Time Frame: Day 90
Measured in IMV, IMV-ECLS and FLUDRO-1 and WAVEFORM domains
Day 90
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).
Time Frame: 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
Time Frame: 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.
Days alive at day 180 after inclusion
Time Frame: Day 180
Measured in WAVEFORM domains
Day 180
Incidence of abnormal PVIs in each ventilation strategy
Time Frame: 7 days
Measured in WAVEFORM domain
7 days
Sedation and NMBA use, type, simultaneous and cumulative dose
Time Frame: 7 days, 28 days
Measured in WAVEFORM domain
7 days, 28 days
Vasopressor use, type, simultaneous and cumulative dose
Time Frame: 7 days, 28 days
Measured in WAVEFORM domain
7 days, 28 days
PTSD symptoms (IES-R)
Time Frame: Day 180
Measured in WAVEFORM domain
Day 180
Cognitive status (MoCA-BLIND)
Time Frame: Day 180
Measured in WAVEFORM domain
Day 180

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Collaborators

University Health Network, Toronto

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 30, 2023

Primary Completion (Estimated)

March 31, 2027

Study Completion (Estimated)

March 31, 2027

Study Registration Dates

First Submitted

November 10, 2021

First Submitted That Met QC Criteria

June 27, 2022

First Posted (Actual)

July 1, 2022

Study Record Updates

Last Update Posted (Actual)

May 7, 2026

Last Update Submitted That Met QC Criteria

May 1, 2026

Last Verified

December 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 21-5940

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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