Extracorporeal Membrane Oxygenation Complication, Mechanical Ventilation Pressure High, Respiratory Insufficiency
Conditions
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.
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.
Interventions
OTHERUltra-Protective Ventilation Facilitated by Extracorporeal Support
Patients randomized to this intervention group will receive VV-ECMO with the ventilator set to minimize driving pressure and respiratory rate for ultra-protective ventilation.
OTHERLung-Protective Ventilation (LPV)
Patients randomized to LPV will receive standard of care lung-protective ventilation with conventional limits on tidal volume and plateau airway pressure.
OTHERDriving Pressure-Limited Ventilation (DPL)
Patients randomized to DPL will receive mechanical ventilation set to maintain a safe limit on driving pressure and plateau airway pressure, without less for the tidal volume.
OTHERLung- and Diaphragm-Protective Ventilation and Sedation (LDPVS)
Patients randomized to LDPVS will have ventilation and sedation adjusted to maintain lung-distending pressure and respiratory effort in a safe target range.
DRUGEarly Cohort corticosteroid dose
Patients randomized to receive corticosteroids will receive dexamethasone 20mg daily for 5 days and then 10mg for an additional 5 days, for a total of 10 days from the time of randomization (or until ICU discharge or death, whichever comes first); after 10 days dexamethasone will be stopped without a taper.
DRUGExtended Cohort corticosteroid dose
Patients randomized to receive extended corticosteroids will receive dexamethasone 10mg for an additional 10 days. At the end of the additional 10 days (day 20 of corticosteroids), the dexamethasone dose will be halved to 5mg for another 5 days (to reduce the risk of adrenal insufficiency) and then stopped (a total of 25 days or until ICU discharge or death, whichever comes first).
DRUGUsual care without routine corticosteroids
Patients randomized to this arm will be managed according to usual care. They will receive corticosteroids only if prescribed by the clinician.
DRUGUsual care without extending corticosteroids
Corticosteroids will stop after 10 days. Other management will be according to usual care. Patients will receive corticosteroids only if prescribed by the clinician.
DRUGUsual care with fludrocortisone
Best practice standard of care prescribed by treating team + fludrocortisone 50μg enterally daily for 7 days.
DRUGUsual care without fludrocortisone
Best practice standard of care prescribed by treating team without fludrocortisone. After randomization, if a clinical indication develops for fludrocortisone as part of standard of care, administration of fludrocortisone is not prohibited. Any fludrocortisone administered to participants in the control arm will be documented.
DRUGDrug 4 mL:
4 mL of nebulized 0.9% saline minutes every 6 hours over 30 minutes every 6 hours.
DRUGDrug 40 mg:
40 mg of nebulized furosemide in 4 mL of saline nebulized over 30 minutes every 6 hours
OTHERPEEP-20
fixed high positive end-expiratory pressure at 20 cmH2O
OTHERPEEP-AOP
positive end-expiratory pressure set according to airway opening pressure
OTHERPEEP-10
fixed lower positive end-expiratory pressure at 10 cmH2O
OTHERVV ECMO-facilitated strategy of earlier awakening, extubation and rehabilitation
Patients randomized to this intervention group will receive VV-ECMO where the sedation will be reduced and the ventilator will will be adjusted to facilitate spontaneous breathing.
OTHERElectrical impedance tomography (EIT)
Patients randomized to EIT will have PEEP titration compared via the Overdistension Collapse Intercept (ODCL) versus that obtained using a standard high PEEP table.
OTHERno treatment / intervention arm is involved
This trial is a prospective, multicenter, observational study (no treatment arm is involved).
OTHERUsual care
Patients will be treated according to usual care.
OTHEREarly Routine IMT
* Training commences once patients meet readiness to wean criteria * 3 sets of 10 breaths, delivered twice daily using a device placed at the airway opening to apply an external resistive pressure load, until hospital discharge, death, or day 45 after randomization, whichever occurs first. * Device load will initially be set to 30% of the MIP. * Device load will be titrated upward (in increments of 5-10% of MIP, to a maximum of 60% of MIP) as needed to achieve a modified Borg dyspnea score of 7/10 or visible accessory muscle use.
OTHERno treatment / intervention arm is involved.
This trial is a prospective, multicenter, observational study (no treatment arm is involved).
Sponsors
University Health Network, Toronto
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
PRACTICAL Platform Inclusion Criteria: 1. Acute hypoxemic respiratory failure meeting all of the following criteria; 1. New or worsening respiratory symptoms developing within 2 weeks prior to the onset of need for oxygen or respiratory support 2. Receiving any of the following types of oxygen or respiratory support for at least 4 hours prior to the time of randomization; supplemental oxygen at 10 L/min or higher, high flow nasal oxygen (at any flow rate), invasive ventilator support, extra-corporeal life support (ECLS), or non-invasive ventilator support 3. Minimum FiO2 ≥ 0.40 (for venturi mask, high flow nasal cannula, or invasive or non-invasive ventilation) or oxygen flow rate ≥10 L/min on face mask for at least 4 hours at the time of evaluation for eligibility unless already on extra-corporeal life support 2. Age ≥ 18 years 3. Hypoxemia not primarily attributable to acute heart failure, fluid overload, or pulmonary embolism (PE) PRACTICAL Platform
Exclusion criteria
1. Extubation is planned or anticipated on the day of screening 2. ICU discharged is planned or anticipated on the day of screening 3. If the patient is moribund and deemed unlikely to survive 24 hours (as determined by the clinical team) 4. If the patient is being transitioned to a fully palliative philosophy of care EXPAND-ECLS Domain Inclusion Criteria: 1. Receiving invasive Endotracheal mechanical ventilation for ≤ 72 hours.5 days 2. Early Moderate-severe hypoxemic respiratory failure with a PaO2/FiO2≤150200 mmHg for at least 6 hours EXPAND-ECLS Domain
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| WAVEFORM domain | considering death as a competing event | Duration of mechanical ventilation (MV) |
| ESCAPE domain - 28-day all-cause mortality | 28-day | — |
| IMPROV domain - recruitment rate, protocol adherence, and vital status | Throughout trial enrollment for recruitment rate and protocol adherence, and up to day 90 for vital status. | ≥0.75 patients randomized per site per month, Protocol adherence defined as \> 80% across participants, and ≥89% ascertainment of vital status and days alive and at home at day 90. |
| 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. | 2 years of active site enrollment. | Record total number of patients randomized, total number of patients eligible yet not randomized, and the number of active randomizing sites on a monthly basis. This will include evaluating the validity and appropriateness of inclusion and exclusion criteria, trial acceptability, and reasons for lack of consent or withdrawal. |
| FLUDRO-1 and IMV domains - ventilator-free days to day 28 in DPL vs LPV (DRIVE RCT) | Day 28 post randomization | Ventilator-free days to day 28 is computed as an ordinal scale ranging between -1 to 28. Patients who die in hospital will be assigned a value of -1. Otherwise the endpoint will be computed from the number of days alive and free of ventilation in the period between the day the patient is liberated from mechanical ventilation and day 28. |
| IMV domain - adherence to LDPVS management (LANDMARK RCT) | Day 28 | Adherence to LDPVS management will be measured in terms of the proportion of protocol-specified measurements of respiratory effort that are on target during the intervention period. |
| IMV domain - probability of achieving and maintaining lung- and diaphragm-protective targets during mechanical ventilation (LANDMARK RCT) | Day 28 | Lung- and diaphragm-protective targets are defined as an estimated dynamic trans pulmonary driving pressure ≤23 cm H2O and a Pocc value between -6 to -20 cm H2O. |
| IMV domain - protocol adherence (EIT intervention) | Day 9 | Protocol adherence will be measured as a binary outcome daily, while patients are receiving EIT. The target protocol adherence across patients is ≥80%. |
| CORT-E2 domain - 60-day mortality from the day of randomization | Day 60 | — |
| FLUDRO-1 domain - Successful enrollment of participants | 18-month enrolment period across three platform trials (PRACTICAL, REMAP-CAP and ATTACC-CAP) | Protocol adherence: e.g., proportion of participants randomized to fludrocortisone who received the study drug as specified in the protocol; Consent rate; Early withdrawal from domain intervention; Outcome completeness |
| FAST-3 domain - Advanced respiratory support free days | Day 28 | Advanced respiratory support free days (ARSFDs) to day 28, a composite outcome including mortality and requirement for respiratory support |
| IMV-ECLS domain - feasibility of enrollment and protocol adherence | For feasibility of enrollment: 2 years of active site enrollment; For protocol adherence, these will be evaluated at 7 days (once the intervention period ends) | Feasibility of enrollment defined as ≥1 patient enrolled per month per site. Protocol adherence defined as ≥90% of patients initiated on assigned PEEP strategy within 6 hours of ECLS cannulation and ≥90% average protocol adherence across participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of NIV | Until ICU discharge, typically within 28 days | Measured in CORT-E2 domain |
| Duration of supplemental oxygen use | Until ICU discharge, typically within 28 days | Measured in CORT-E2 domain |
| Need for ECLS | Until ICU discharge, typically within 28 days | Measured in CORT-E2 domain |
| Duration of ECLS, only for patients who require ECLS | Until ICU discharge, typically within 28 days | Measured in CORT-E2, IMV-ECLS domains. |
| 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). | Until day 30 for CORT-E2, and until day 28 for FAST-3, FLUDRO-1, ULTIMATE and WAVEFORM | Measured in CORT-E2, FAST-3, FLUDRO-1, ULTIMATE and WAVEFORM domains. |
| EQ-5-D at day 180 | For CORT-E2, FAST-3, IMV, and IMV-ECLS domains: Day 180; For IMPROV domain: Day 90 and Day 180. | Measured in CORT-E2, FAST-3, IMV, IMV-ECLS, IMPROV, WAVEFORM domains |
| Montreal Cognitive Assessment (MoCA) At day 180 | Day 180 | Measured in FAST-3 domain |
| Complications from corticosteroids. | Until hospital discharge, assessed up to 4 weeks | Measured in CORT-E2 domain. Hypernatremia, hyperglycemia, delirium, clinically important GI bleeding, nosocomial infection, neuromuscular weakness. Measured in FLUDRO-1 domain: Hypernatremia, Hyperglycemia, Hypokalemia, Clinically important gastrointestinal bleeding, New nosocomial infection |
| Reintubation during index ICU admission | Until ICU discharge, typically within 28 days | Measured in IMV, IMV-ECLS domains |
| Number of reintubations up to tracheostomy during index hospitalization | Until hospital discharge | Measured in IMPROV domain |
| Tracheostomy during index ICU admission | Until ICU discharge, typically within 28 days | Measured in IMV, IMV-ECLS, IMPROV domains |
| Re-cannulation to ECLS during index ICU admission | Until ICU discharge, typically within 28 days | Measured in IMV-ECLS domain |
| Sequential Organ Failure Assessment (SOFA) score | Daily, for duration of intervention | Measured in IMV, IMV-ECLS domains |
| Respiratory mechanics and gas exchange - Driving pressure. | Daily, for duration of intervention | Measured in IMV, IMV-ECLS domains. |
| Respiratory mechanics and gas exchange - Pocc. | Daily, for duration of intervention | Measured in IMV, IMV-ECLS domains. |
| Respiratory mechanics and gas exchange - P0.1 | Daily, for duration of intervention | Measured in IMV, IMV-ECLS domains. |
| Respiratory mechanics and gas exchange - plateau airway pressure | Daily, for duration of intervention | Measured in IMV, IMV-ECLS domains. |
| Respiratory mechanics and gas exchange - P/F ratio | Daily, for duration of intervention | Measured in IMV, IMV-ECLS domains. |
| Respiratory mechanics and gas exchange - ventilatory ratio | Daily, for duration of intervention | Measured in IMV domain. |
| Diaphragm thickness | Daily, for duration of intervention | Measured in IMV domain |
| Maximal diaphragm thickening fraction | During first SBT | Measured in IMV domain |
| Survival status at disconnection from mechanical ventilation (dead or alive) | Until day 28 | Measured in EXPAND-ECLS domain |
| Organ failure-free days | Until day 28 | Measured in ESCAPE, FLUDRO-1 domains |
| Modified Lung Injury Score (mLIS) | Until day 10 | Measured in IMV-EIT intervention. Calculated daily up until study day 10 in patients who are alive and continue to have acute hypoxemic respiratory failure requiring invasive mechanical ventilation. |
| Number of days from first SBT to disconnection from mechanical ventilation | Until ICU discharge | Measured in IMPROV domain - final date of extubation or the first day of continuous tracheostomy mask for at least 24 hours, provided ventilator support is not resumed during the index ICU admission. |
| Barotrauma during hospital admission | Until 45 days or hospital discharge | Measured in IMPROV domain including pneumothorax, pneumomediastinum, subcutaneous emphysema |
| Cardiac arrest during hospital admission | Until 45 days or hospital discharge | Measured in IMPROV domain |
| 30 second sit to stand test at ICU discharge and hospital discharge | Until ICU discharge, typically within 28 days | Measured in IMPROV domain |
| Modified Medical Research Council (mMRC) Dyspnea Scale | At ICU discharge, Day 90, Day 180 | Measured in IMPROV domain |
| Physical function (Activity Measure for Post-Acute Care) | At ICU discharge, Day 90, Day 180 | Measured in IMPROV domain |
| Days alive at day 180 after inclusion | Day 180 | Measured in WAVEFORM domains |
| Incidence of abnormal PVIs in each ventilation strategy | 7 days | Measured in WAVEFORM domain |
| Sedation and NMBA use, type, simultaneous and cumulative dose | 7 days, 28 days | Measured in WAVEFORM domain |
| Vasopressor use, type, simultaneous and cumulative dose | 7 days, 28 days | Measured in WAVEFORM domain |
| PTSD symptoms (IES-R) | Day 180 | Measured in WAVEFORM domain |
| Cognitive status (MoCA-BLIND) | Day 180 | Measured in WAVEFORM domain |
| Serious adverse events (SAEs) | Throughout the trial | Serious adverse events (SAEs) related to the intervention measured in FAST-3 domain |
| To assess adherence to our explicit mechanical ventilation protocols. | 48 hours | Adherence to protocol defined as \>80% of patients having \<20% of monitored values determined to be major protocol deviations. |
| To measure and understand the reasons for crossovers in each group | 2 years | Success for lack of crossovers defined as \<10% of crossovers between groups (when not allowed by protocol) in either direction. |
| Duration of mechanical ventilation during index ICU admission | Until ICU discharge, typically within 28 days | Measured in CORT-E2, IMV, IMV-ECLS and EXPAND-ECLS domains |
| 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 | Measured in CORT-E2, ESCAPE, FAST-3, IMV, IMV-ECLS, IMPROV and EXPAND-ECLS and WAVEFORM domains |
| Vital status | Day 90 and at 6 months | Measured in IMPROV domain |
| Duration of ICU admission | Until ICU discharge, typically within 28 days | Measured in FAST-3, IMV, IMV-ECLS and EXPAND-ECLS and WAVEFORM domains |
| Hospital length of stay | Until hospital discharge, assessed up to 4 weeks | Measured in CORT-E2, FAST-3, IMV, IMV-ECLS and WAVEFORM domains |
| ICU and hospital free days | For FAST-3: ICU discharge, hospital discharge, Day 28. For IMPROV: Day 90. | Measured in FAST-3, IMPROV domains |
| Discharge disposition. | Until hospital discharge, assessed up to 4 weeks | Measured in IMV, IMV-ECLS, IMPROV domains. Location to which patient is discharged (e.g., home, weaning facility, etc.) |
| Days alive and at home to day 90 | Day 90 | Measured in IMV, IMV-ECLS and FLUDRO-1 and WAVEFORM domains |
| Need for ICU readmission prior to hospital discharge | Until hospital discharge, assessed up to 4 weeks | Measured in IMV, IMV-ECLS domains |
Countries
Australia, Canada, Colombia, Italy, New Zealand, Saudi Arabia, Singapore, Spain, United States
Contacts
CONTACTRongyu ( Cindy) Jin
CONTACTCathy Chau
STUDY_CHAIREwan Goligher, MD, PhD
University Health Network, Toronto
STUDY_CHAIREddy Fan, MD, PhD
University Health Network, Toronto
PRINCIPAL_INVESTIGATORNiall Ferguson, MD, MSc
University Health Network, Toronto
PRINCIPAL_INVESTIGATORLorenzo Del Sorbo, MD
University Health Network, Toronto
PRINCIPAL_INVESTIGATORBram Rochwerg, MD, MSc
McMaster University
PRINCIPAL_INVESTIGATORBijan Teja, MD
Unity Health Toronto
PRINCIPAL_INVESTIGATORJohn Muscedere, MD
Queens University
PRINCIPAL_INVESTIGATORLaveena Munshi, MD
Mount Sinai Hospital, Canada
PRINCIPAL_INVESTIGATORDmitry Rozenberg, MD, PhD
University Health Network, Toronto
PRINCIPAL_INVESTIGATORAnastasia Newman, PhD
McMaster University
PRINCIPAL_INVESTIGATORIrene Telias, MD, PhD
University Health Network, Toronto
PRINCIPAL_INVESTIGATORAndrea Castellvi Font, MD, PhD
Parc de Salut Mar, Spain
PRINCIPAL_INVESTIGATORLaurent Brochard, MD
Unity Health Toronto
Outcome results
None listed