Platform of Randomized Adaptive Clinical Trials in Critical Illness

NCT05440851 | Recruiting DMC

• 1 other identifier: 21-5940
• Study Type: interventional
• Target: 6,250
• Locations: 9 countries
• Sites: 89

Brief Summary

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.

Conditions

Respiratory Insufficiency; Mechanical Ventilation Pressure High; Extracorporeal Membrane Oxygenation Complication

Outcome Measures

Primary Outcomes (12)

• 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.

  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)

  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)

  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)

  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)

  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

• CORT-E2 domain - 60-day mortality from the day of randomization

  Day 60

• FLUDRO-1 domain - Successful enrollment of participants

  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

  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

  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)

• ESCAPE domain - 28-day all-cause mortality

  28-day

• IMPROV domain - recruitment rate, protocol adherence, and 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

  Duration of mechanical ventilation (MV)

  considering death as a competing event

Secondary Outcomes (48)

• To assess adherence to our explicit mechanical ventilation protocols.

  48 hours

• To measure and understand the reasons for crossovers in each group

  2 years

• Duration of mechanical ventilation during index ICU admission

  Until ICU discharge, typically within 28 days

• Mortality at other endpoints

  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

  Day 90 and at 6 months

Study Arms (10)

Ultra-protective ventilation facilitated by extracorporeal carbon dioxide removal.

OTHER

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: Ultra-Protective Ventilation Facilitated by Extracorporeal Support; Other: Lung-Protective Ventilation (LPV); Other: VV ECMO-facilitated strategy of earlier awakening, extubation and rehabilitation

Invasive Mechanical Ventilation (IMV) Strategies domain

OTHER

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); Other: Driving Pressure-Limited Ventilation (DPL); Other: Lung- and Diaphragm-Protective Ventilation and Sedation (LDPVS); Other: Electrical impedance tomography (EIT)

The Corticosteroid Early and Extended (CORT-E2) Randomized Controlled Trial domain

OTHER

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; Drug: Extended Cohort corticosteroid dose; Drug: Usual care without routine corticosteroids; Drug: Usual care without extending corticosteroids

The Nebulized Furosemide for the Treatment of Pulmonary Inflammation (FAST-3) domain

OTHER

Patients with Respiratory Failure Secondary to Pulmonary Infection.

Drug: Drug 4 mL:; Drug: Drug 40 mg:

The Invasive Mechanical Ventilation Strategies in Venovenous-Extracorporeal Life Support (IMV-ECLS)

OTHER

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; Other: PEEP-AOP; Other: PEEP-10

The Fludrocortisone in Acute Hypoxemic Respiratory Failure with Airspace Disease (FLUDRO-1) domain

OTHER

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

Drug: Usual care with fludrocortisone; Drug: Usual care without fludrocortisone

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

OTHER

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: Ultra-Protective Ventilation Facilitated by Extracorporeal Support; Other: Lung-Protective Ventilation (LPV); Other: VV ECMO-facilitated strategy of earlier awakening, extubation and rehabilitation

Evaluating Subphenotypes in Immunocompromized Patients with ARF (ESCAPE) Domain

OTHER

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

Inspiratory Muscle Training in Patients Receiving Ongoing Mechanical Ventilation (IMPROV) Domain

OTHER

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

Other: Usual care; Other: Early Routine IMT

Clinical Implications of Potentially Injurious Patient-Ventilator Interactions (WAVEFORM) Domain

OTHER

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.

Interventions

Ultra-Protective Ventilation Facilitated by Extracorporeal Support OTHER

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.

Ultra-protective ventilation facilitated by extracorporeal carbon dioxide removal.; VV ECMO-facilitated strategy of earlier awakening, extubation and rehabilitation

Drug 4 mL: DRUG

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

The Nebulized Furosemide for the Treatment of Pulmonary Inflammation (FAST-3) domain

Drug 40 mg: DRUG

40 mg of nebulized furosemide in 4 mL of saline nebulized over 30 minutes every 6 hours

The Nebulized Furosemide for the Treatment of Pulmonary Inflammation (FAST-3) domain

Lung-Protective Ventilation (LPV) OTHER

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

Invasive Mechanical Ventilation (IMV) Strategies domain; Ultra-protective ventilation facilitated by extracorporeal carbon dioxide removal.; VV ECMO-facilitated strategy of earlier awakening, extubation and rehabilitation

Driving Pressure-Limited Ventilation (DPL) OTHER

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.

Invasive Mechanical Ventilation (IMV) Strategies domain

Lung- and Diaphragm-Protective Ventilation and Sedation (LDPVS) OTHER

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

Invasive Mechanical Ventilation (IMV) Strategies domain

Early Cohort corticosteroid dose DRUG

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.

The Corticosteroid Early and Extended (CORT-E2) Randomized Controlled Trial domain

Extended Cohort corticosteroid dose DRUG

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).

The Corticosteroid Early and Extended (CORT-E2) Randomized Controlled Trial domain

Usual care without routine corticosteroids DRUG

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

The Corticosteroid Early and Extended (CORT-E2) Randomized Controlled Trial domain

Usual care without extending corticosteroids DRUG

Corticosteroids will stop after 10 days. Other management will be according to usual care. Patients will receive corticosteroids only if prescribed by the clinician.

The Corticosteroid Early and Extended (CORT-E2) Randomized Controlled Trial domain

Usual care with fludrocortisone DRUG

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

The Fludrocortisone in Acute Hypoxemic Respiratory Failure with Airspace Disease (FLUDRO-1) domain

Usual care without fludrocortisone DRUG

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.

The Fludrocortisone in Acute Hypoxemic Respiratory Failure with Airspace Disease (FLUDRO-1) domain

PEEP-20 OTHER

fixed high positive end-expiratory pressure at 20 cmH2O

The Invasive Mechanical Ventilation Strategies in Venovenous-Extracorporeal Life Support (IMV-ECLS)

PEEP-AOP OTHER

positive end-expiratory pressure set according to airway opening pressure

The Invasive Mechanical Ventilation Strategies in Venovenous-Extracorporeal Life Support (IMV-ECLS)

PEEP-10 OTHER

fixed lower positive end-expiratory pressure at 10 cmH2O

The Invasive Mechanical Ventilation Strategies in Venovenous-Extracorporeal Life Support (IMV-ECLS)

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

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.

Ultra-protective ventilation facilitated by extracorporeal carbon dioxide removal.; VV ECMO-facilitated strategy of earlier awakening, extubation and rehabilitation

Electrical impedance tomography (EIT) OTHER

Patients randomized to EIT will have PEEP titration compared via the Overdistension Collapse Intercept (ODCL) versus that obtained using a standard high PEEP table.

Invasive Mechanical Ventilation (IMV) Strategies domain

no treatment / intervention arm is involved. OTHER

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

Clinical Implications of Potentially Injurious Patient-Ventilator Interactions (WAVEFORM) Domain

Usual care OTHER

Patients will be treated according to usual care.

Inspiratory Muscle Training in Patients Receiving Ongoing Mechanical Ventilation (IMPROV) Domain

Early Routine IMT OTHER

* 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.

Inspiratory Muscle Training in Patients Receiving Ongoing Mechanical Ventilation (IMPROV) Domain

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Acute hypoxemic respiratory failure meeting all of the following criteria;
• New or worsening respiratory symptoms developing within 2 weeks prior to the onset of need for oxygen or respiratory support
• 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
• 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
• Age ≥ 18 years
• Hypoxemia not primarily attributable to acute heart failure, fluid overload, or pulmonary embolism (PE)

You may not qualify if:

• Extubation is planned or anticipated on the day of screening
• ICU discharged is planned or anticipated on the day of screening
• If the patient is moribund and deemed unlikely to survive 24 hours (as determined by the clinical team)
• If the patient is being transitioned to a fully palliative philosophy of care
• Receiving invasive Endotracheal mechanical ventilation for ≤ 72 hours.5 days
• Early Moderate-severe hypoxemic respiratory failure with a PaO2/FiO2≤150200 mmHg for at least 6 hours
• Patients over 70 years of age.
• Currently receiving any form of ECLS (e.g., Venovenous, venoarterial, or hybrid configuration).
• Chronic hypercapnic respiratory failure defined as PaCO2 \> 60 mmHg in the outpatient setting.
• Home mechanical ventilation (non-invasive ventilation or via tracheotomy) except for CPAP/BiPAP used solely for sleep-disordered breathing.
• Actual body weight exceeding 1 kg per centimeter of height.
• Severe hypoxemia with PaO2/FiO2 \< 80mmHg for \> 6 hours at time of screening.
• Severe hypercapnic respiratory failure with pH \< 7.25 and PaCO2 \> 60 mmHg for \> 6 hours at time of screening.
• Expected mechanical ventilation duration \< 48 hours at time of screening.
• Confirmed diffuse alveolar hemorrhage from vasculitis.

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (89)

University of Arizona

Tucson, Arizona, 85724, United States

RECRUITING

University of California Los Angeles (UCLA)

Los Angeles, California, 90095, United States

RECRUITING

University of San Diego (UCSD)

San Diego, California, 92121, United States

RECRUITING

University of California San Francisco

San Francisco, California, 94143, United States

RECRUITING

University of Colorado Hospital

Aurora, Colorado, 80045, United States

RECRUITING

University of Kentucky

Lexington, Kentucky, 40506, United States

RECRUITING

University of Maryland Medical System

Baltimore, Maryland, 21201, United States

RECRUITING

The Johns Hopkins Medicine

Baltimore, Maryland, 21224, United States

RECRUITING

VA Ann Arbor Healthcare System

Ann Arbor, Michigan, 48105, United States

NOT YET RECRUITING

University of Michigan Health

Ann Arbor, Michigan, 48109, United States

RECRUITING

Washington University

St Louis, Missouri, 63130, United States

RECRUITING

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

RECRUITING

Mount Sinai New York City

New York, New York, 10029, United States

RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

Wake Forest University School of Medicine

Winston-Salem, North Carolina, 27101, United States

RECRUITING

University of Cincinnati College of Medicine

Cincinnati, Ohio, 45267, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

Oregon Health & Science University (OHSU)

Portland, Oregon, 97239, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

University of Pittsburgh Medical Center (UPMC)

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

RECRUITING

Medical University of South Carolina (MUSC)

Charleston, South Carolina, 29425, United States

RECRUITING

Vanderbilt university medical center

Nashville, Tennessee, 37232, United States

RECRUITING

University of Utah Health

Farmington, Utah, 84025, United States

RECRUITING

Sentara Health

Norfolk, Virginia, 23507, United States

RECRUITING

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

RECRUITING

Nepean Hospital

Kingswood, New South Wales, 2747, Australia

RECRUITING

Wollongong Hospital

Wollongong, New South Wales, 2500, Australia

RECRUITING

Flinders Medical Centre

Bedford Park, Southern Adelaide, 5042, Australia

RECRUITING

St Vincents Sydney

Darlinghurst, Sydney, 2010, Australia

RECRUITING

Bendigo Health Victoria

Bendigo, Victoria, 3550, Australia

RECRUITING

University Hospital Geelong

Geelong, Victoria, 3220, Australia

RECRUITING

The Austin Hospital

Heidelberg, Victoria, 3084, Australia

RECRUITING

University of Calgary

Calgary, Alberta, T2N 1N4, Canada

RECRUITING

University of Alberta/Edmonton University Hospital

Edmonton, Alberta, T6G 2X8, Canada

RECRUITING

Nanaimo Regional General Hospital

Nanaimo, British Columbia, V9S 2B7, Canada

RECRUITING

Surrey Memorial Hospital

Surrey, British Columbia, V3V 1Z2, Canada

RECRUITING

St. Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

RECRUITING

Royal Jubilee Hospital

Victoria, British Columbia, V8R 1J8, Canada

RECRUITING

Vancouver Island Health - Royal Jubilee Hospital & Nanaimo Hospital

Victoria, British Columbia, V8R 1J8, Canada

RECRUITING

St. Boniface Hospital

Winnipeg, Manitoba, R2H 2A6, Canada

RECRUITING

Health Sciences Centre - Winnipeg

Winnipeg, Manitoba, R3A 1R9, Canada

RECRUITING

Grace Hospital

Winnipeg, Manitoba, R3J 3M7, Canada

RECRUITING

Nova Scotia Health Authority

Halifax, Nova Scotia, B3S 0H6, Canada

RECRUITING

William Osler Health System

Brampton, Ontario, L6R 3J7, Canada

RECRUITING

Brantford General Hospital

Brantford, Ontario, N3R 1G9, Canada

RECRUITING

Hamilton Health Sciences Centre - General

Hamilton, Ontario, L8L 2X2, Canada

RECRUITING

St. Joseph's Hamilton

Hamilton, Ontario, L8N 4A6, Canada

RECRUITING

Hamilton Health Sciences Centre - Juravinski

Hamilton, Ontario, L8V 1C3, Canada

RECRUITING

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

RECRUITING

London Health Sciences Centre - University Hospital

London, Ontario, N6A 5W9, Canada

NOT YET RECRUITING

London Health Sciences Centre - Victoria Hospital

London, Ontario, N6A 5W9, Canada

NOT YET RECRUITING

Oak Valley Health

Markham, Ontario, L3P 7P3, Canada

RECRUITING

North York General Hospital

North York, Ontario, M2K 1E1, Canada

RECRUITING

Halton Healthcare

Oakville, Ontario, L6M 0L8, Canada

RECRUITING

Lakeridge Hospital

Oshawa, Ontario, L1G 8A2, Canada

RECRUITING

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

RECRUITING

Ottawa Heart Research Institute

Ottawa, Ontario, K1Y 4W7, Canada

NOT YET RECRUITING

Mackenzie Health

Richmond Hill, Ontario, L4C 4Z3, Canada

RECRUITING

Niagara Health Systems

Saint Catherines, Ontario, L2S 0A9, Canada

RECRUITING

Scarborough Health Network

Toronto, Ontario, M1P 2V5, Canada

RECRUITING

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

Unity Health Toronto

Toronto, Ontario, M5C 2T2, Canada

RECRUITING

Sinai Health, Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

RECRUITING

University Health Network

Toronto, Ontario, Canada

RECRUITING

Cortellucci Vaughan Hospital

Vaughan, Ontario, L6A 4Z3, Canada

RECRUITING

Windsor Regional Health

Windsor, Ontario, N8W 1L9, Canada

RECRUITING

Cité de la Santé Hospital

Laval, Quebec, H7M 3L9, Canada

NOT YET RECRUITING

Centre hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, H2X 0C1, Canada

RECRUITING

MUHC - McGill University Health Centre (Glen Site)

Montreal, Quebec, H4A 0B1, Canada

RECRUITING

Sacre Coeur du Montreal

Montreal, Quebec, H4J 1C5, Canada

RECRUITING

Centre Hospitalier Universite de Sherbrooke

Sherbrooke, Quebec, J1J 3H5, Canada

RECRUITING

Trois Riviere (CHAUR)

Trois-Rivières, Quebec, G8Z 3R9, Canada

RECRUITING

University of Saskatchewan

Saskatoon, Saskatchewan, S7N 0W8, Canada

RECRUITING

Clínica Universidad de La Sabana

Chía, Cundinamarca, Colombia

RECRUITING

Universidad de La Sabana

Chía, Cundinamarca, Colombia

RECRUITING

Azienda Socio-Sanitaria Territoriale Ovest Milanese

Legnano, MI, 20025, Italy

RECRUITING

Ospedale Maggiore, Fondazione IRCCS Ca Granda, Milano

Milan, MI, 20122, Italy

RECRUITING

ASST Grande Ospedale Metropolitano Niguarda

Milan, MI, 20162, Italy

RECRUITING

Auckland City Hospital

Grafton, Auckland, 1023, New Zealand

RECRUITING

Middlemore Hospital

Auckland, 2025, New Zealand

RECRUITING

Taranaki Base Hospital

New Plymouth, 4310, New Zealand

RECRUITING

Rotorua Hospital

Rotorua, 3010, New Zealand

RECRUITING

King Abdulaziz Medical City- Riyadh

Riyadh, 11426, Saudi Arabia

RECRUITING

National University of Singapore

Singapore, 119077, Singapore

RECRUITING

Parc Taulí University Hospital

Sabadell, Barcelona, 08208, Spain

ACTIVE NOT RECRUITING

Hospital Universitario de Getafe

Getafe, Madrid, 28905, Spain

NOT YET RECRUITING

Hospital Josep Trueta (Girona)

Girona, 17007, Spain

RECRUITING

MeSH Terms

Conditions

Respiratory Insufficiency

Interventions

Fludrocortisone; Pharmaceutical Preparations; Airway Extubation; Rehabilitation

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Hydrocortisone; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Airway Management; Therapeutics; Investigative Techniques; Aftercare; Continuity of Patient Care; Patient Care; Health Services; Health Care Facilities Workforce and Services

Study Officials

• Ewan Goligher, MD, PhD

  University Health Network, Toronto

  STUDY CHAIR

• Eddy Fan, MD, PhD

  University Health Network, Toronto

  STUDY CHAIR

• Niall Ferguson, MD, MSc

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

• Lorenzo Del Sorbo, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

• Bram Rochwerg, MD, MSc

  McMaster University

  PRINCIPAL INVESTIGATOR

• Bijan Teja, MD

  Unity Health Toronto

  PRINCIPAL INVESTIGATOR

• John Muscedere, MD

  Queens University

  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

  PRINCIPAL INVESTIGATOR

• Laurent Brochard, MD

  Unity Health Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rongyu ( Cindy) Jin

CONTACT

4163404800; rongyu.jin@uhn.ca

Cathy Chau

CONTACT

4167272260; cathy.chau@uhn.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: While blinding of treatment allocation is an important mechanism for mitigating bias, the nature of acute hypoxemic respiratory failure and the complexity of interventions to be tested in PRACTICAL may make it difficult to blind treatment allocation in some cases. Blinded allocation will be implemented where possible. Where possible, clinical outcomes will be collected by research personnel who are masked to randomized treatment assignment. Even where research personnel cannot be blinded to treatment assignment, bias arising will be mitigated by selection of relatively objective endpoints not easily influenced by knowledge of treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2021
• First Posted: July 1, 2022
• Study Start: April 30, 2023
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: May 7, 2026

Record last verified: 2025-12

Locations

IT (3); SA (1); NZ (4); US (26); CO (2); CA (41); SG (1); ES (3); AU (8)