AzTrials
AzTrials

Respiratory InsufficiencyPRACTICALNCT05440851

Platform of Randomized Adaptive Clinical Trials in Critical Illness

A study testing Ultra-Protective Ventilation Facilitated by Extracorporeal Support, Lung-Protective Ventilation (LPV) and Driving Pressure-Limited Ventilation (DPL) in people with Respiratory Insufficiency and Extracorporeal Membrane Oxygenation Complication, run by University Health Network, Toronto at 103 sites in 10 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record

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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ultra-Protective Ventilation Facilitated by Extracorporeal Support, Lung-Protective Ventilation (LPV) and Driving Pressure-Limited Ventilation (DPL)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6,250 participants
Where
103 sitesin 10 countries
Study dates
30 Apr 2023to 31 Mar 2027
Phase
Interventional

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

PRACTICAL Platform Inclusion Criteria:

  1. Acute hypoxemic respiratory failure meeting all of the following criteria;
  2. New or worsening respiratory symptoms developing within 2 weeks prior to the onset of need for oxygen or respiratory support
  3. 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
  4. 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
  5. Age ≥ 18 years
  6. 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:
  2. 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)
  3. 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.
  4. 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
  8. Patients whom are deemed palliative. WAVEFORM Domain Inclusion Criteria
  9. Patient is intubated at the time of eligibility assessment. WAVEFORM Domain Exclusion Criteria
  10. PaO2/FiO2 >300 mm Hg or (S/F >250, if PaO2/FiO2 has not been measured) at the time of eligibility assessment.
  11. Duration of mechanical ventilation during current ICU admission is ≥72 hours.
  12. Receiving ECLS without continuous invasive mechanical ventilatory support. IMV-ECLS Domain Inclusion Criteria
  13. 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
  14. Patients receiving invasive mechanical ventilation for AHRF as defined by the PRACTICAL platform trial criteria above.
  15. Within 7 calendar days of intubation IMPROV Domain Exclusion Criteria
  16. Patient is expected to be liberated from mechanical ventilation within 24 hours
  17. Known or suspected chronic hypercapnic respiratory failure defined as PaCO2>60mmHg in the outpatient setting
  18. 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
  19. Known pneumothorax or pneumomediastinum without chest tube placement sustained during current ICU admission* (re-confirm immediately prior to randomization)
  20. Patient is admitted primarily for acute brain injury (stroke, traumatic brain injury, etc.)
  21. Previously diagnosed chronic neuromuscular disorder
  22. Patient has an implantable cardiac defibrillator or pacemaker
  23. Planned to be transferred to another hospital before ICU discharge
  24. Already receiving a regimen of inspiratory muscle training using external resistive device or diaphragm neurostimulation

Trial locations and contacts

103 sites in 10 countries. Contact the study team or a site near you to ask about taking part.

Rongyu ( Cindy) Jin contact

4163404800 ext. 7613

rongyu.jin@uhn.ca

Cathy Chau contact

4167272260

cathy.chau@uhn.ca

103 sites in 10 countries

Canada41 sites, 41 recruiting

  • William Osler Health System

    Brampton, Ontario, L6R 3J7

    Alexandra Binnie, 416-494-2120, alexandra.binnie@gmail.com

    Recruiting

  • Brantford General Hospital

    Brantford, Ontario, N3R 1G9

    Brenda Reeve, 519-751-5544, reeveb@mcmaster.ca

    Recruiting

  • University of Calgary

    Calgary, Alberta, T2N 1N4

    Ken Parhar, 403-944-0735, ksparhar@ucalgary.ca

    Recruiting

  • University of Alberta/Edmonton University Hospital

    Edmonton, Alberta, T6G 2X8

    Fernando Zampieri, 780-492-9951, fzampier@ualberta.ca

    Sean Bagshaw

    Recruiting

  • Nova Scotia Health Authority

    Halifax, Nova Scotia, B3S 0H6

    Edmund Chong-How Tan, 902-473-3608, cetan@dal.ca

    Recruiting

  • Hamilton Health Sciences Centre - General

    Hamilton, Ontario, L8L 2X2

    Alison E Fox-Robichaud, 905-521-2100, afoxrob@mcmaster.ca

    Recruiting

  • St. Joseph's Hamilton

    Hamilton, Ontario, L8N 4A6

    Deborah Cook, 905-525-9140 ext. 23162, debcook@mcmaster.ca

    Recruiting

  • Hamilton Health Sciences Centre - Juravinski

    Hamilton, Ontario, L8V 1C3

    Bram Rochwerg, 905-521-2100, bram.rochwerg@gmail.com

    Recruiting

  • Kingston Health Sciences Centre

    Kingston, Ontario, K7L 2V7

    John Muscedere, 613-549-6666 ext. 4642, john.muscedere@kingstonhsc.ca

    Dave Maslove

    Recruiting

  • Cité de la Santé Hospital

    Laval, Quebec, H7M 3L9

    Marios Roussos, 450-668-1010, marios.roussos.med@ssss.gouv.qc.ca

    Recruiting

  • London Health Sciences Centre - University Hospital

    London, Ontario, N6A 5W9

    Karen Bosma, 519-685-8500, KarenJ.Bosma@lhsc.on.ca

    Recruiting

  • London Health Sciences Centre - Victoria Hospital

    London, Ontario, N6A 5W9

    John Landau, 519-685-8044, john.landau@lhsc.on.ca

    Not yet recruiting

  • Oak Valley Health

    Markham, Ontario, L3P 7P3

    Dipayan Chaudhuri, 905-472-7373, dipayan.chaudhuri@medportal.ca

    Recruiting

  • Centre hospitalier de l'Université de Montréal (CHUM)

    Montreal, Quebec, H2X 0C1

    Martin Girard, 514-890-8000 ext. 12131, martin.girard@umontreal.ca

    Recruiting

  • MUHC - McGill University Health Centre (Glen Site)

    Montreal, Quebec, H4A 0B1

    Douglas Slobod, 514-934-1934, douglas.slobod@mcgill.ca

    Recruiting

  • Sacre Coeur du Montreal

    Montreal, Quebec, H4J 1C5

    Yiorgos Alexandros Cavayas, 514-343-6111 ext. 38492, yiorgos.alexandros.cavayas.med@ssss.gouv.qc.ca

    Martin Albert, 514-338-2959, m.albert@umontreal.ca

    Recruiting

  • Nanaimo Regional General Hospital

    Nanaimo, British Columbia, V9S 2B7

    Daniel Ovakim, 250-370-8000, Daniel.Ovakim@islandhealth.ca

    Recruiting

  • North York General Hospital

    North York, Ontario, M2K 1E1

    Anna Geagea, 416-756-6000, anna.geagea@nygh.on.ca

    Recruiting

  • Halton Healthcare

    Oakville, Ontario, L6M 0L8

    Sonny Kohli, 905-338-4618, skohli@haltonhealthcare.com

    Recruiting

  • Lakeridge Hospital

    Oshawa, Ontario, L1G 8A2

    Shannon Fernando, 905-576-8711, sfernando@qmed.ca

    Karim Soliman, 905-576-8711 ext. 33720, ksoliman@lh.ca

    Recruiting

  • The Ottawa Hospital

    Ottawa, Ontario, K1H 8L6

    Alexandra Fottinger, 613-737-8899, afottinger@toh.ca

    Recruiting

  • Ottawa Heart Research Institute

    Ottawa, Ontario, K1Y 4W7

    Brent Wilson, 613-696-7381, browilson@ottawaheart.ca

    Not yet recruiting

  • Mackenzie Health

    Richmond Hill, Ontario, L4C 4Z3

    Dave Paskar, 905-883-1212 ext. 3306, dave.paskar@mackenziehealth.ca

    Recruiting

  • Niagara Health Systems

    Saint Catherines, Ontario, L2S 0A9

    Jennifer Tsang, 905-684-7271 ext. 42919, jennifer.tsang@niagarahealth.on.ca

    Recruiting

  • University of Saskatchewan

    Saskatoon, Saskatchewan, S7N 0W8

    Sabira Valiani, 306-655-2035, svaliani@usask.ca

    Recruiting

  • Centre Hospitalier Universite de Sherbrooke

    Sherbrooke, Quebec, J1J 3H5

    Francois Lamontagne, 819-821-8000 ext. 74977, francois.lamontagne@usherbrooke.ca

    Recruiting

  • Surrey Memorial Hospital

    Surrey, British Columbia, V3V 1Z2

    Anish Mitra, 604-875-4111 ext. 69586, anish.r.mitra@gmail.com

    Recruiting

  • Scarborough Health Network

    Toronto, Ontario, M1P 2V5

    Christopher J Yarnell, 416-438-2911, cyarnell@shn.ca

    Recruiting

  • Sunnybrook Health Sciences Centre

    Toronto, Ontario, M4N 3M5

    Neill Adhikari, 416-480-4522, neill.adhikari@sunnybrook.ca

    Recruiting

  • Unity Health Toronto

    Toronto, Ontario, M5C 2T2

    Laurent Brochard, 416-864-5686, Laurent.Brochard@unityhealth.to

    Jan Friedrich

    Recruiting

  • Sinai Health, Mount Sinai Hospital

    Toronto, Ontario, M5G 1X5

    Laveena Munshi, 416-586-4800 ext. 5133, laveena.munshi@sinaihealth.ca

    Recruiting

  • University Health Network

    Toronto, Ontario

    Ewan Goligher, 416-340-4800 ext. 6810, ewan.goligher@uhn.ca

    Eddy Fan, 416-340-4800 ext. 5483, eddy.fan@uhn.ca

    Recruiting

  • Trois Riviere (CHAUR)

    Trois-Rivières, Quebec, G8Z 3R9

    Jean-Francois Naud, 450-687-8801, jean-francois.naud@inrs.ca

    Recruiting

  • St. Paul's Hospital

    Vancouver, British Columbia, V6Z 1Y6

    John Boyd, 604-682-2344 ext. 63047, john.boyd@hli.ubc.ca

    Recruiting

  • Cortellucci Vaughan Hospital

    Vaughan, Ontario, L6A 4Z3

    Kimia Honarmand, 905-417-2000, kimia.honarmand@mackenziehealth.ca

    Recruiting

  • Royal Jubilee Hospital

    Victoria, British Columbia, V8R 1J8

    Daniel Ovakim, 250-370-8000, daniel.ovakim@islandhealth.ca

    Gordon Wood

    Recruiting

  • Vancouver Island Health - Royal Jubilee Hospital & Nanaimo Hospital

    Victoria, British Columbia, V8R 1J8

    Gordon Wood, 250-370-8000, gordon.wood@islandhealth.ca

    Daniel Ovakim, 250-370-8000, daniel.ovakim@islandhealth.ca

    Recruiting

  • Windsor Regional Health

    Windsor, Ontario, N8W 1L9

    Adam Rahman, 519-646-6100 ext. 64320, adam.rahman@sjhc.london.on.ca

    Recruiting

  • St. Boniface Hospital

    Winnipeg, Manitoba, R2H 2A6

    Owen Mooney, 204-237-2825, owenthomas.mooney@umanitoba.ca

    Recruiting

  • Health Sciences Centre - Winnipeg

    Winnipeg, Manitoba, R3A 1R9

    Clare Ramsey, 204-787-7772, cramsey@hsc.mb.ca

    Gloria Grande

    Recruiting

  • Grace Hospital

    Winnipeg, Manitoba, R3J 3M7

    Marcus Blouw, 204-837-0111, mblouw@hsc.mb.ca

    Recruiting

Other trials in Canada

United States27 sites, 27 recruiting

  • VA Ann Arbor Healthcare System

    Ann Arbor, Michigan, 48105

    Jane C Deng, 734-249-1048, jcdeng@umich.edu

    Recruiting

  • University of Michigan Health

    Ann Arbor, Michigan, 48109

    Robert C Hyzy, 888-287-1084, rhyzy@med.umich.edu

    Recruiting

  • University of Colorado Hospital

    Aurora, Colorado, 80045

    Neil Aggarwal, 303-724-5375, neil.aggarwal@cuanschutz.edu

    Recruiting

  • University of Maryland Medical System

    Baltimore, Maryland, 21201

    Carl Shanholtz, 410-328-8141, cshanhol@medicine.umaryland.edu

    Recruiting

  • The Johns Hopkins Medicine

    Baltimore, Maryland, 21224

    Sarina Sahetya, 410-955-5000, ssahetya@jhmi.edu

    Recruiting

  • Medical University of South Carolina (MUSC)

    Charleston, South Carolina, 29425

    Andrew Goodwin, 843-792-4728, goodwian@musc.edu

    Recruiting

  • University of Cincinnati College of Medicine

    Cincinnati, Ohio, 45267

    Dina Gomaa, 513-558-7333, gomaada@ucmail.uc.edu

    Recruiting

  • Cleveland Clinic

    Cleveland, Ohio, 44195

    Abhijit Duggal, 216-444-2200, duggala2@ccf.org

    Recruiting

  • Texas Tech

    El Paso, Texas, 79905

    Juan B Figueroa, (915) 215-5200, Juan.B.Figueroa@ttuhsc.edu

    Recruiting

  • University of Utah Health

    Farmington, Utah, 84025

    Andrew Freeman, 801-213-3200, andrew.freeman@hsc.utah.edu

    Recruiting

  • University of Kentucky

    Lexington, Kentucky, 40506

    Anil Gopinath, 859-257-1000, ago233@uky.edu

    Parijat Sen, parijatsen@uky.edu

    Recruiting

  • University of California Los Angeles (UCLA)

    Los Angeles, California, 90095

    Steven Y. Chang, 310-825-8061, sychang@mednet.ucla.edu

    Recruiting

  • Vanderbilt university medical center

    Nashville, Tennessee, 37232

    Kevin Seitz, 615-322-5000, kevin.seitz@vumc.org

    Todd Rice, (615) 322-5000, todd.rice@vumc.org

    Recruiting

  • Mount Sinai New York City

    New York, New York, 10029

    Neha N Goel, 646-888-4298, neha.goel@mountsinai.org

    Recruiting

  • Columbia University Irving Medical Center

    New York, New York, 10032

    Matthew R Baldwin, 212-342-4676, mrb45@cumc.columbia.edu

    Richard Greendyk, 212-305-4141, richard.greendyk@uhn.ca

    Recruiting

  • Sentara Health

    Norfolk, Virginia, 23507

    Xian Qiao, 757-388-6115, xxqiao@sentara.com

    Recruiting

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

    Keely Buesing, 402-599-8908, keely.buesing@unmc.edu

    Recruiting

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

    John Reilly, 630-790-1872, john.reilly@pennmedicine.upenn.edu

    Recruiting

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

    Michael Baram, 215-955-6591, michael.baram@jefferson.edu

    Recruiting

  • University of Pittsburgh Medical Center (UPMC)

    Pittsburgh, Pennsylvania, 15213

    Bryan McVerry, 412-624-8905, Bryan.Mcverry@va.gov

    Recruiting

  • Oregon Health & Science University (OHSU)

    Portland, Oregon, 97239

    Akram Khan, 503-494-8311, khana@ohsu.edu

    Recruiting

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

    Maya Cohen, 401-444-5773, maya_cohen@brown.edu

    Recruiting

  • University of San Diego (UCSD)

    San Diego, California, 92121

    Atul Malhotra, 844-757-5337, amalhotra@health.ucsd.edu

    Recruiting

  • University of California San Francisco

    San Francisco, California, 94143

    Michael Matthay, 415-353-1206, michael.matthay@ucsf.edu

    Recruiting

  • Washington University

    St Louis, Missouri, 63130

    Bryan Kraft, 314-454-8762, kraft@wustl.edu

    Recruiting

  • University of Arizona

    Tucson, Arizona, 85724

    Jarrod Mosier, 520-626-6312, jmosier@aemrc.arizona.edu

    Recruiting

  • Wake Forest University School of Medicine

    Winston-Salem, North Carolina, 27101

    Kevin Ward Gibbs, 336-716-2011, kevin.gibbs@advocatehealth.org

    Recruiting

Other trials in United States

Australia11 sites, 11 recruiting

  • Flinders Medical Centre

    Bedford Park, Southern Adelaide, 5042

    Shailesh Bihari, MBBS, MD, FCICM, DDU, PhD, 08-8201-3911, shailesh.bihari@flinders.edu.au

    Recruiting

  • Bendigo Health Victoria

    Bendigo, Victoria, 3550

    Cameron Knott, cknott@bendigohealth.org.au

    Recruiting

  • Royal Prince Alfred Hospital

    Camperdown, New South Wales, 2050

    Elliot Worku, 612-9515-6111, Elliott.Worku@health.nsw.gov.au

    Recruiting

  • The Prince Charles Hospital

    Chermside, Queensland, 4032

    Gianluigu Li Bassi, 61 (7) 3139 6880, g.libassi@uq.edu.au

    Recruiting

  • St Vincent Hospital, Sydney

    Darlinghurst, Sydney, 2010

    Stephen Morgan, stephen.morgan@svha.org.au

    Recruiting

  • Peninsula University Hospital

    Frankston, Victoria, 3199

    Ravindranath Tiruvoipati, (03) 9784 7423, ravindranath.tiruvoipati@monash.edu

    Recruiting

  • University Hospital Geelong

    Geelong, Victoria, 3220

    Erfana Thasneem, 0403603545, Erfana.Thashneem@barwonheaIth.erg.au

    Recruiting

  • The Austin Hospital

    Heidelberg, Victoria, 3084

    Ary Serpa Neto, 613-9496-5000, ary.serpaneto@monash.edu

    Recruiting

  • Nepean Hospital

    Kingswood, New South Wales, 2747

    Ian Seppelt, 02-4734-1166, ian.seppelt@sydney.edu.au

    Recruiting

  • Westmead Hospital

    Westmead, 2145

    Hatem Elkady, (02) 8890 5555, hatem.elkady@health.nsw.gov.au

    Recruiting

  • Wollongong Hospital

    Wollongong, New South Wales, 2500

    Matthew MacPartlin, 02-4222-5000, matthew.macpartlin@health.nsw.gov.au

    Recruiting

Other trials in Australia

Italy9 sites, 9 recruiting

  • Azienda Ospedaliero-Universitaria di Ferrara

    Cona, Ferrara, 44124

    Savino Spadaro, +39 0532 236111, spdsvn@unife.it

    Recruiting

  • Policlinico Riuniti Foggia

    Foggia, FG, 71122

    Lucia Mirabella, +39 0881 731111, lucia.mirabella@unifg.it

    Recruiting

  • Azienda Socio-Sanitaria Territoriale Ovest Milanese

    Legnano, MI, 20025

    Giovanni Mistraletti, 0331 449458, giovanni.mistraletti@asst-ovestmi.it

    Recruiting

  • Ospedale Maggiore, Fondazione IRCCS Ca Granda, Milano

    Milan, Michigan, 20122

    Giacomo Grasselli, +39 02 50320193, giacomo.grasselli@unimi.it

    Recruiting

  • ASST Grande Ospedale Metropolitano Niguarda

    Milan, Michigan, 20162

    Thomas Langer, +39 0264448580, thomas.langer@unimib.it

    Recruiting

  • Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

    Palermo, PA, 90127

    Andrea Cortegiani, +39 091 655 1111, andrea.cortegiani@unipa.it

    Recruiting

  • Policlinico Universitario Agostino Gemelli

    Roma, RM, 00168

    Domenico Grieco, +39 06 30151, domenicoluca.grieco@unicatt.it

    Recruiting

  • Azienda Ospedaliero Universitaria - Sassari

    Sassari, SS, 07100

    Pierpaolo Terragni, +39 079 206 1000, pierpaolo.terragni@aouss.it

    Recruiting

  • Ospedale Santa Chiara di Trento

    Trento, TN, 38122

    Giacomo Bellani, +39 0461 903111, giacomo.bellani@apss.tn.it

    Recruiting

Other trials in Italy

Spain6 sites, 5 recruiting

  • Hospital del Mar

    Ciutat Vella, Barcelona, 08003

    Francisco José Parrilla-Gomez, +34 932 48 30 00, fparrilla@hmar.cat

    Recruiting

  • Hospital Josep Trueta (Girona)

    Girona, 17007

    Claudia Vera Ching, +34 972 94 02 00, cvera79@hotmail.com

    Recruiting

  • Vall d'Hebron University Hospital

    Horta-Guinardó, Barcelona, 08035

    Andrés Pacheco, +34 934 893 000, andresfrancisco.pacheco@vallhebron.cat

    Recruiting

  • Bellvitge University Hospital

    L'Hospitalet de Llobregat, Barcelona, 08907

    Oriol Roca, +34 932 60 75 00, oriol.roca@bellvitgehospital.cat

    Recruiting

  • Parc Taulí University Hospital

    Sabadell, Barcelona, 08208

    Active, not recruiting

  • Hospital U Virgen de la Candelaria

    Santa Cruz de Tenerife, 38010

    Raquel Montiel, +34 922 60 20 00, raquelmontiel@gmail.com

    Recruiting

Other trials in Spain

New Zealand5 sites, 5 recruiting

  • Middlemore Hospital

    Auckland, 2025

    Tony Williams, (09) 276 0000, Tony.Williams@cmdhb.org.nz

    Recruiting

  • Auckland City Hospital

    Grafton, Auckland, 1023

    Tobias Gonzenbach, (09) 375 7100, TobiasG@adhb.govt.nz

    Recruiting

  • Waikato Hospital

    Hamilton, New Zealand, 3204

    Meghan McInerny, +64 7 839 8899, meghan.mcinerney@waikatodhb.health.nz

    Recruiting

  • Taranaki Base Hospital

    New Plymouth, 4310

    Jonathan Albrett, 06 753 6139, Jonathan.Albrett@tdhb.org.nz

    Recruiting

  • Rotorua Hospital

    Rotorua, 3010

    Ulrike Buehner, +64 (07) 348 1199, Ulrike.Buehner@lakesdhb.govt.nz

    Recruiting

Other trials in New Zealand

Colombia1 site, 1 recruiting

  • Clínica Universidad de La Sabana

    Chía, Cundinamarca

    Luis Felipe Reyes, 57-317-513-0128, luis.reyes5@unisabana.edu.co

    Recruiting

Other trials in Colombia

Hong Kong1 site, 1 recruiting

  • Queen Mary Hospital

    Hong Kong

    Pauline Yeung, (852) 3910-3372, pyeungng@hku.hk

    Alfred Wong, dr.askwong@gmail.com

    Recruiting

Other trials in Hong Kong

Saudi Arabia1 site, 1 recruiting

  • King Abdulaziz Medical City- Riyadh

    Riyadh, 11426

    Yaseen Arabi, +966 (11) 801-1111 ext. 18855, arabi@mngha.med.sa

    Recruiting

Other trials in Saudi Arabia

Singapore1 site, 1 recruiting

  • National University of Singapore

    Singapore, 119077

    Matthew Edward Cove, +65 6908 2222, matthew_edward_cove@nuhs.edu.sg

    Recruiting

Other trials in Singapore

About this study

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.

Read more

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.

Read the 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.

Being tested
Ultra-Protective Ventilation Facilitated by Extracorporeal Support, Lung-Protective Ventilation (LPV), Driving Pressure-Limited Ventilation (DPL), Lung- and Diaphragm-Protective Ventilation and Sedation (LDPVS), Early Cohort corticosteroid dose
Medical subject headings
Respiratory Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ultra-Protective Ventilation Facilitated by Extracorporeal SupportOther

    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.

  • 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.

  • 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.

  • 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.

  • Early Cohort corticosteroid doseDrug

    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.

  • Extended Cohort corticosteroid doseDrug

    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).

  • Usual care without routine corticosteroidsDrug

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

  • Usual care without extending corticosteroidsDrug

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

  • Usual care with fludrocortisoneDrug

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

  • Usual care without fludrocortisoneDrug

    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.

  • Drug 4 mL:Drug

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

  • Drug 40 mg:Drug

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

  • PEEP-20Other

    fixed high positive end-expiratory pressure at 20 cmH2O

  • PEEP-AOPOther

    positive end-expiratory pressure set according to airway opening pressure

  • PEEP-10Other

    fixed lower positive end-expiratory pressure at 10 cmH2O

  • VV ECMO-facilitated strategy of earlier awakening, extubation and rehabilitationOther

    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.

  • 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.

  • no treatment / intervention arm is involvedOther

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

  • Usual careOther

    Patients will be treated according to usual care.

  • Early Routine IMTOther

    • 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.

  • no treatment / intervention arm is involved.Other

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

Study groups in NCT05440851
Study groupRoleWhat they receive
Ultra-protective ventilation facilitated by extracorporeal carbon dioxide removal.OtherPatients 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.
Receives: 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 domainOtherPatients 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.
Receives: 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 domainOtherPatients 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.
Receives: 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) domainOtherPatients with Respiratory Failure Secondary to Pulmonary Infection.
Receives: Drug: Drug 4 mL:; Drug: Drug 40 mg:
The Invasive Mechanical Ventilation Strategies in Venovenous-Extracorporeal Life Support (IMV-ECLS)OtherPatients with acute hypoxemic respiratory failure receiving extracorporeal life support will be randomized to one of three positive end-expiratory pressure (PEEP) strategies.
Receives: Other: PEEP-20; Other: PEEP-AOP; Other: PEEP-10
The Fludrocortisone in Acute Hypoxemic Respiratory Failure with Airspace Disease (FLUDRO-1) domainOtherPatients with acute hypoxemic respiratory failure with airspace disease will be randomized to usual care with or without fludrocortisone.
Receives: Drug: Usual care with fludrocortisone; Drug: Usual care without fludrocortisone
VV ECMO-facilitated strategy of earlier awakening, extubation and rehabilitationOtherPatients 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.
Receives: 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) DomainOtherWe 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.
Receives: Other: no treatment / intervention arm is involved
Inspiratory Muscle Training in Patients Receiving Ongoing Mechanical Ventilation (IMPROV) DomainOtherThis domain studies inspiratory muscle training (IMT) during and after mechanical ventilation in patients with acute hypoxemic respiratory failure (AHRF).
Receives: Other: Usual care; Other: Early Routine IMT
Clinical Implications of Potentially Injurious Patient-Ventilator Interactions (WAVEFORM) DomainOtherThis domain primarily aims at understanding the short-and long-term clinical consequences of longitudinal exposure to abnormal patient ventilator interactions.
Receives: Other: no treatment / intervention arm is involved.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 2 years of active site enrollment.

  2. 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.

    Measured: Day 28 post randomization

  3. 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.

    Measured: Day 28

  4. 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.

    Measured: Day 28

  5. 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%.

    Measured: Day 9

  6. CORT-E2 domain - 60-day mortality from the day of randomization

    Measured: Day 60

  7. 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

    Measured: 18-month enrolment period across three platform trials (PRACTICAL, REMAP-CAP and ATTACC-CAP)

  8. 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

    Measured: Day 28

  9. 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.

    Measured: 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)

  10. ESCAPE domain - 28-day all-cause mortality

    Measured: 28-day

  11. 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.

    Measured: Throughout trial enrollment for recruitment rate and protocol adherence, and up to day 90 for vital status.

  12. WAVEFORM domain

    Duration of mechanical ventilation (MV)

    Measured: considering death as a competing event

Secondary outcomes (48)

  1. To assess adherence to our explicit mechanical ventilation protocols.

    Adherence to protocol defined as >80% of patients having <20% of monitored values determined to be major protocol deviations.

    Measured: 48 hours

  2. To measure and understand the reasons for crossovers in each group

    Success for lack of crossovers defined as <10% of crossovers between groups (when not allowed by protocol) in either direction.

    Measured: 2 years

  3. Duration of mechanical ventilation during index ICU admission

    Measured in CORT-E2, IMV, IMV-ECLS and EXPAND-ECLS domains

    Measured: Until ICU discharge, typically within 28 days

  4. Mortality at other endpoints

    Measured in CORT-E2, ESCAPE, FAST-3, IMV, IMV-ECLS, IMPROV and EXPAND-ECLS and WAVEFORM domains

    Measured: 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

  5. Vital status

    Measured in IMPROV domain

    Measured: Day 90 and at 6 months

  6. Duration of ICU admission

    Measured in FAST-3, IMV, IMV-ECLS and EXPAND-ECLS and WAVEFORM domains

    Measured: Until ICU discharge, typically within 28 days

  7. Hospital length of stay

    Measured in CORT-E2, FAST-3, IMV, IMV-ECLS and WAVEFORM domains

    Measured: Until hospital discharge, assessed up to 4 weeks

  8. ICU and hospital free days

    Measured in FAST-3, IMPROV domains

    Measured: For FAST-3: ICU discharge, hospital discharge, Day 28. For IMPROV: Day 90.

  9. Discharge disposition.

    Measured in IMV, IMV-ECLS, IMPROV domains. Location to which patient is discharged (e.g., home, weaning facility, etc.)

    Measured: Until hospital discharge, assessed up to 4 weeks

  10. Days alive and at home to day 90

    Measured in IMV, IMV-ECLS and FLUDRO-1 and WAVEFORM domains

    Measured: Day 90

  11. Need for ICU readmission prior to hospital discharge

    Measured in IMV, IMV-ECLS domains

    Measured: Until hospital discharge, assessed up to 4 weeks

  12. Duration of NIV

    Measured in CORT-E2 domain

    Measured: Until ICU discharge, typically within 28 days

  13. Duration of supplemental oxygen use

    Measured in CORT-E2 domain

    Measured: Until ICU discharge, typically within 28 days

  14. Need for ECLS

    Measured in CORT-E2 domain

    Measured: Until ICU discharge, typically within 28 days

  15. Duration of ECLS, only for patients who require ECLS

    Measured in CORT-E2, IMV-ECLS domains.

    Measured: Until ICU discharge, typically within 28 days

  16. 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).

    Measured in CORT-E2, FAST-3, FLUDRO-1, ULTIMATE and WAVEFORM domains.

    Measured: Until day 30 for CORT-E2, and until day 28 for FAST-3, FLUDRO-1, ULTIMATE and WAVEFORM

  17. EQ-5-D at day 180

    Measured in CORT-E2, FAST-3, IMV, IMV-ECLS, IMPROV, WAVEFORM domains

    Measured: For CORT-E2, FAST-3, IMV, and IMV-ECLS domains: Day 180; For IMPROV domain: Day 90 and Day 180.

  18. Montreal Cognitive Assessment (MoCA) At day 180

    Measured in FAST-3 domain

    Measured: Day 180

  19. Complications from corticosteroids.

    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

    Measured: Until hospital discharge, assessed up to 4 weeks

  20. Reintubation during index ICU admission

    Measured in IMV, IMV-ECLS domains

    Measured: Until ICU discharge, typically within 28 days

  21. Number of reintubations up to tracheostomy during index hospitalization

    Measured in IMPROV domain

    Measured: Until hospital discharge

  22. Tracheostomy during index ICU admission

    Measured in IMV, IMV-ECLS, IMPROV domains

    Measured: Until ICU discharge, typically within 28 days

  23. Re-cannulation to ECLS during index ICU admission

    Measured in IMV-ECLS domain

    Measured: Until ICU discharge, typically within 28 days

  24. Sequential Organ Failure Assessment (SOFA) score

    Measured in IMV, IMV-ECLS domains

    Measured: Daily, for duration of intervention

  25. Respiratory mechanics and gas exchange - Driving pressure.

    Measured in IMV, IMV-ECLS domains.

    Measured: Daily, for duration of intervention

  26. Respiratory mechanics and gas exchange - Pocc.

    Measured in IMV, IMV-ECLS domains.

    Measured: Daily, for duration of intervention

  27. Respiratory mechanics and gas exchange - P0.1

    Measured in IMV, IMV-ECLS domains.

    Measured: Daily, for duration of intervention

  28. Respiratory mechanics and gas exchange - plateau airway pressure

    Measured in IMV, IMV-ECLS domains.

    Measured: Daily, for duration of intervention

  29. Respiratory mechanics and gas exchange - P/F ratio

    Measured in IMV, IMV-ECLS domains.

    Measured: Daily, for duration of intervention

  30. Respiratory mechanics and gas exchange - ventilatory ratio

    Measured in IMV domain.

    Measured: Daily, for duration of intervention

  31. Diaphragm thickness

    Measured in IMV domain

    Measured: Daily, for duration of intervention

  32. Maximal diaphragm thickening fraction

    Measured in IMV domain

    Measured: During first SBT

  33. Survival status at disconnection from mechanical ventilation (dead or alive)

    Measured in EXPAND-ECLS domain

    Measured: Until day 28

  34. Organ failure-free days

    Measured in ESCAPE, FLUDRO-1 domains

    Measured: Until day 28

  35. Serious adverse events (SAEs)

    Serious adverse events (SAEs) related to the intervention measured in FAST-3 domain

    Measured: Throughout the trial

  36. Modified Lung Injury Score (mLIS)

    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.

    Measured: Until day 10

  37. Number of days from first SBT to disconnection from mechanical ventilation

    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.

    Measured: Until ICU discharge

  38. Barotrauma during hospital admission

    Measured in IMPROV domain including pneumothorax, pneumomediastinum, subcutaneous emphysema

    Measured: Until 45 days or hospital discharge

  39. Cardiac arrest during hospital admission

    Measured in IMPROV domain

    Measured: Until 45 days or hospital discharge

  40. 30 second sit to stand test at ICU discharge and hospital discharge

    Measured in IMPROV domain

    Measured: Until ICU discharge, typically within 28 days

  41. Modified Medical Research Council (mMRC) Dyspnea Scale

    Measured in IMPROV domain

    Measured: At ICU discharge, Day 90, Day 180

  42. Physical function (Activity Measure for Post-Acute Care)

    Measured in IMPROV domain

    Measured: At ICU discharge, Day 90, Day 180

  43. Days alive at day 180 after inclusion

    Measured in WAVEFORM domains

    Measured: Day 180

  44. Incidence of abnormal PVIs in each ventilation strategy

    Measured in WAVEFORM domain

    Measured: 7 days

  45. Sedation and NMBA use, type, simultaneous and cumulative dose

    Measured in WAVEFORM domain

    Measured: 7 days, 28 days

  46. Vasopressor use, type, simultaneous and cumulative dose

    Measured in WAVEFORM domain

    Measured: 7 days, 28 days

  47. PTSD symptoms (IES-R)

    Measured in WAVEFORM domain

    Measured: Day 180

  48. Cognitive status (MoCA-BLIND)

    Measured in WAVEFORM domain

    Measured: Day 180

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Jul 2022
  2. Study start30 Apr 2023
  3. Primary completion31 Mar 2027 (estimated)
  4. Study completion31 Mar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
6,250 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05440851
Sponsor's protocol ID
21-5940
Acronym
PRACTICAL
Status last verified
Dec 2025
First submitted
10 Nov 2021
Last updated
22 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

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