Massive trial aims to find best treatments for breathing failure in ICU patients

NCT ID NCT05440851

Knowledge-focused Sponsor: University Health Network, Toronto Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Jun 27, 2026

Summary

This study is testing many different treatments for patients with severe breathing problems in the intensive care unit. It will include up to 6,250 participants and looks at various approaches like breathing machine settings, medications, and life support techniques. The goal is to find which treatments work best to help patients survive and recover.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Not a phased trial

Phase numbers describe drug development. The registry uses this when they do not apply, as it does for trials of devices, procedures or behaviour changes, and for observational studies.

Participants

About 6,250 people

The number the study aims to enrol. It can still change while the study runs.

Started

Apr 2023

Expected to finish

Mar 2027

An estimate. End dates often move.

Lead sponsor

Other sponsor

The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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

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Conditions

The condition(s) this trial relates to.

acute respiratory failure respiratory failure

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Extracorporeal membrane oxygenation complication Mechanical ventilation pressure high Respiratory insufficiency

How to take part

Only the study team decides who joins. These are the ways to reach them.

The places running it

88 sites in 9 countries. The list below names each one and where it is.
The official record

ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.

Open the record ↗
A doctor treating you

A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.

Contacts and locations

Locations

ASST Grande Ospedale Metropolitano Niguarda
RECRUITING

Milan, MI, 20162, Italy
Auckland City Hospital
RECRUITING

Grafton, Auckland, 1023, New Zealand
Azienda Socio-Sanitaria Territoriale Ovest Milanese
RECRUITING

Legnano, MI, 20025, Italy
Bendigo Health Victoria
RECRUITING

Bendigo, Victoria, 3550, Australia
Brantford General Hospital
RECRUITING

Brantford, Ontario, N3R 1G9, Canada
Centre Hospitalier Universite de Sherbrooke
RECRUITING

Sherbrooke, Quebec, J1J 3H5, Canada
Centre hospitalier de l'Université de Montréal (CHUM)
RECRUITING

Montreal, Quebec, H2X 0C1, Canada
Cité de la Santé Hospital
NOT_YET_RECRUITING

Laval, Quebec, H7M 3L9, Canada
Cleveland Clinic
RECRUITING

Cleveland, Ohio, 44195, United States
Clínica Universidad de La Sabana
RECRUITING

Chía, Cundinamarca, Colombia
Columbia University Irving Medical Center
RECRUITING

New York, New York, 10032, United States
Cortellucci Vaughan Hospital
RECRUITING

Vaughan, Ontario, L6A 4Z3, Canada
Flinders Medical Centre
RECRUITING

Bedford Park, Southern Adelaide, 5042, Australia
Grace Hospital
RECRUITING

Winnipeg, Manitoba, R3J 3M7, Canada
Halton Healthcare
RECRUITING

Oakville, Ontario, L6M 0L8, Canada
Hamilton Health Sciences Centre - General
RECRUITING

Hamilton, Ontario, L8L 2X2, Canada
Hamilton Health Sciences Centre - Juravinski
RECRUITING

Hamilton, Ontario, L8V 1C3, Canada
Health Sciences Centre - Winnipeg
RECRUITING

Winnipeg, Manitoba, R3A 1R9, Canada
Hospital Josep Trueta (Girona)
RECRUITING

Girona, 17007, Spain
Hospital Universitario de Getafe
NOT_YET_RECRUITING

Getafe, Madrid, 28905, Spain
King Abdulaziz Medical City- Riyadh
RECRUITING

Riyadh, 11426, Saudi Arabia
Kingston Health Sciences Centre
RECRUITING

Kingston, Ontario, K7L 2V7, Canada
Lakeridge Hospital
RECRUITING

Oshawa, Ontario, L1G 8A2, Canada
London Health Sciences Centre - University Hospital
NOT_YET_RECRUITING

London, Ontario, N6A 5W9, Canada
London Health Sciences Centre - Victoria Hospital
NOT_YET_RECRUITING

London, Ontario, N6A 5W9, Canada
MUHC - McGill University Health Centre (Glen Site)
RECRUITING

Montreal, Quebec, H4A 0B1, Canada
Mackenzie Health
RECRUITING

Richmond Hill, Ontario, L4C 4Z3, Canada
Medical University of South Carolina (MUSC)
RECRUITING

Charleston, South Carolina, 29425, United States
Middlemore Hospital
RECRUITING

Auckland, 2025, New Zealand
Mount Sinai New York City
RECRUITING

New York, New York, 10029, United States
Nanaimo Regional General Hospital
RECRUITING

Nanaimo, British Columbia, V9S 2B7, Canada
National University of Singapore
RECRUITING

Singapore, 119077, Singapore
Nepean Hospital
RECRUITING

Kingswood, New South Wales, 2747, Australia
Niagara Health Systems
RECRUITING

Saint Catherines, Ontario, L2S 0A9, Canada
North York General Hospital
RECRUITING

North York, Ontario, M2K 1E1, Canada
Nova Scotia Health Authority
RECRUITING

Halifax, Nova Scotia, B3S 0H6, Canada
Oak Valley Health
RECRUITING

Markham, Ontario, L3P 7P3, Canada
Oregon Health & Science University (OHSU)
RECRUITING

Portland, Oregon, 97239, United States
Ospedale Maggiore, Fondazione IRCCS Ca Granda, Milano
RECRUITING

Milan, MI, 20122, Italy
Ottawa Heart Research Institute
NOT_YET_RECRUITING

Ottawa, Ontario, K1Y 4W7, Canada
Parc Taulí University Hospital
ACTIVE_NOT_RECRUITING

Sabadell, Barcelona, 08208, Spain
Rhode Island Hospital
RECRUITING

Providence, Rhode Island, 02903, United States
Rotorua Hospital
RECRUITING

Rotorua, 3010, New Zealand
Royal Jubilee Hospital
RECRUITING

Victoria, British Columbia, V8R 1J8, Canada
Royal Prince Alfred Hospital
RECRUITING

Camperdown, New South Wales, 2050, Australia
Sacre Coeur du Montreal
RECRUITING

Montreal, Quebec, H4J 1C5, Canada
Scarborough Health Network
RECRUITING

Toronto, Ontario, M1P 2V5, Canada
Sentara Health
RECRUITING

Norfolk, Virginia, 23507, United States
Sinai Health, Mount Sinai Hospital
RECRUITING

Toronto, Ontario, M5G 1X5, Canada
St Vincents Sydney
RECRUITING

Darlinghurst, Sydney, 2010, Australia
St. Boniface Hospital
RECRUITING

Winnipeg, Manitoba, R2H 2A6, Canada
St. Joseph's Hamilton
RECRUITING

Hamilton, Ontario, L8N 4A6, Canada
St. Paul's Hospital
RECRUITING

Vancouver, British Columbia, V6Z 1Y6, Canada
Sunnybrook Health Sciences Centre
RECRUITING

Toronto, Ontario, M4N 3M5, Canada
Surrey Memorial Hospital
RECRUITING

Surrey, British Columbia, V3V 1Z2, Canada
Taranaki Base Hospital
RECRUITING

New Plymouth, 4310, New Zealand
The Austin Hospital
RECRUITING

Heidelberg, Victoria, 3084, Australia
The Johns Hopkins Medicine
RECRUITING

Baltimore, Maryland, 21224, United States
The Ottawa Hospital
RECRUITING

Ottawa, Ontario, K1H 8L6, Canada
Thomas Jefferson University Hospital
RECRUITING

Philadelphia, Pennsylvania, 19107, United States
Trois Riviere (CHAUR)
RECRUITING

Trois-Rivières, Quebec, G8Z 3R9, Canada
Unity Health Toronto
RECRUITING

Toronto, Ontario, M5C 2T2, Canada
Universidad de La Sabana
RECRUITING

Chía, Cundinamarca, Colombia
University Health Network
RECRUITING

Toronto, Ontario, Canada
University Hospital Geelong
RECRUITING

Geelong, Victoria, 3220, Australia
University of Alberta/Edmonton University Hospital
RECRUITING

Edmonton, Alberta, T6G 2X8, Canada
University of Arizona
RECRUITING

Tucson, Arizona, 85724, United States
University of Calgary
RECRUITING

Calgary, Alberta, T2N 1N4, Canada
University of California Los Angeles (UCLA)
RECRUITING

Los Angeles, California, 90095, United States
University of California San Francisco
RECRUITING

San Francisco, California, 94143, United States
University of Cincinnati College of Medicine
RECRUITING

Cincinnati, Ohio, 45267, United States
University of Colorado Hospital
RECRUITING

Aurora, Colorado, 80045, United States
University of Kentucky
RECRUITING

Lexington, Kentucky, 40506, United States
University of Maryland Medical System
RECRUITING

Baltimore, Maryland, 21201, United States
University of Michigan Health
RECRUITING

Ann Arbor, Michigan, 48109, United States
University of Nebraska Medical Center
RECRUITING

Omaha, Nebraska, 68198, United States
University of Pennsylvania
RECRUITING

Philadelphia, Pennsylvania, 19104, United States
University of Pittsburgh Medical Center (UPMC)
RECRUITING

Pittsburgh, Pennsylvania, 15213, United States
University of San Diego (UCSD)
RECRUITING

San Diego, California, 92121, United States
University of Saskatchewan
RECRUITING

Saskatoon, Saskatchewan, S7N 0W8, Canada
University of Utah Health
RECRUITING

Farmington, Utah, 84025, United States
VA Ann Arbor Healthcare System
NOT_YET_RECRUITING

Ann Arbor, Michigan, 48105, United States
Vancouver Island Health - Royal Jubilee Hospital & Nanaimo Hospital
RECRUITING

Victoria, British Columbia, V8R 1J8, Canada
Vanderbilt university medical center
RECRUITING

Nashville, Tennessee, 37232, United States
Wake Forest University School of Medicine
RECRUITING

Winston-Salem, North Carolina, 27101, United States
Washington University
RECRUITING

St Louis, Missouri, 63130, United States
William Osler Health System
RECRUITING

Brampton, Ontario, L6R 3J7, Canada
Windsor Regional Health
RECRUITING

Windsor, Ontario, N8W 1L9, Canada
Wollongong Hospital
RECRUITING

Wollongong, New South Wales, 2500, Australia

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