Platform of Randomized Adaptive Clinical Trials in Critical Illness (NCT05440851) — Spain Trial Details

Condition(s) studied

Respiratory InsufficiencyExtracorporeal Membrane Oxygenation ComplicationMechanical Ventilation Pressure High

Investigational drug(s) / intervention(s)

Ultra-Protective Ventilation Facilitated by Extracorporeal SupportLung-Protective Ventilation (LPV)Driving Pressure-Limited Ventilation (DPL)Lung- and Diaphragm-Protective Ventilation and Sedation (LDPVS)Early Cohort corticosteroid doseExtended Cohort corticosteroid doseUsual care without routine corticosteroidsUsual care without extending corticosteroidsUsual care with fludrocortisoneUsual care without fludrocortisoneDrug 4 mL:Drug 40 mg:PEEP-20PEEP-AOPPEEP-10VV ECMO-facilitated strategy of earlier awakening, extubation and rehabilitationElectrical impedance tomography (EIT)no treatment / intervention arm is involvedUsual careEarly Routine IMTno treatment / intervention arm is involved.

Ultra-Protective Ventilation Facilitated by Extracorporeal Support: Patients randomized to this intervention group will receive VV-ECMO with the ventilator set to minimize driving pressure and respiratory rate for ultra-protective ventilation.

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

Driving Pressure-Limited Ventilation (DPL): Patients randomized to DPL will receive mechanical ventilation set to maintain a safe limit on driving pressure and plateau airway pressure, without less for the tidal volume.

Lung- and Diaphragm-Protective Ventilation and Sedation (LDPVS): Patients randomized to LDPVS will have ventilation and sedation adjusted to maintain lung-distending pressure and respiratory effort in a safe target range.

Early Cohort corticosteroid dose: Patients randomized to receive corticosteroids will receive dexamethasone 20mg daily for 5 days and then 10mg for an additional 5 days, for a total of 10 days from the time of randomization (or until ICU discharge or death, whichever comes first); after 10 days dexamethasone will be stopped without a taper.

Extended Cohort corticosteroid dose: Patients randomized to receive extended corticosteroids will receive dexamethasone 10mg for an additional 10 days. At the end of the additional 10 days (day 20 of corticosteroids), the dexamethasone dose will be halved to 5mg for another 5 days (to reduce the risk of adrenal insufficiency) and then stopped (a total of 25 days or until ICU discharge or death, whichever comes first).

Usual care without routine corticosteroids: Patients randomized to this arm will be managed according to usual care. They will receive corticosteroids only if prescribed by the clinician.

Usual care without extending corticosteroids: Corticosteroids will stop after 10 days. Other management will be according to usual care. Patients will receive corticosteroids only if prescribed by the clinician.

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

Usual care without fludrocortisone: Best practice standard of care prescribed by treating team without fludrocortisone. After randomization, if a clinical indication develops for fludrocortisone as part of standard of care, administration of fludrocortisone is not prohibited. Any fludrocortisone administered to participants in the control arm will be documented.

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

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

PEEP-20: fixed high positive end-expiratory pressure at 20 cmH2O

PEEP-AOP: positive end-expiratory pressure set according to airway opening pressure

PEEP-10: fixed lower positive end-expiratory pressure at 10 cmH2O

VV ECMO-facilitated strategy of earlier awakening, extubation and rehabilitation: Patients randomized to this intervention group will receive VV-ECMO where the sedation will be reduced and the ventilator will will be adjusted to facilitate spontaneous breathing.

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

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

Usual care: Patients will be treated according to usual care.

Early Routine IMT: * Training commences once patients meet readiness to wean criteria * 3 sets of 10 breaths, delivered twice daily using a device placed at the airway opening to apply an external resistive pressure load, until hospital discharge, death, or day 45 after randomization, whichever occurs first. * Device load will initially be set to 30% of the MIP. * Device load will be titrated upward (in increments of 5-10% of MIP, to a maximum of 60% of MIP) as needed to achieve a modified Borg dyspnea score of 7/10 or visible accessory muscle use.

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

Study 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.

Eligibility

Sex

ALL

Min age

18 Years

Max age

—

Healthy volunteers

No

PRACTICAL Platform Inclusion Criteria: 1. Acute hypoxemic respiratory failure meeting all of the following criteria; 1. New or worsening respiratory symptoms developing within 2 weeks prior to the onset of need for oxygen or respiratory support 2. Receiving any of the following types of oxygen or respiratory support for at least 4 hours prior to the time of randomization; supplemental oxygen at 10 L/min or higher, high flow nasal oxygen (at any flow rate), invasive ventilator support, extra-corporeal life support (ECLS), or non-invasive ventilator support 3. Minimum FiO2 ≥ 0.40 (for venturi mask, high flow nasal cannula, or invasive or non-invasive ventilation) or oxygen flow rate ≥10 L/min on face mask for at least 4 hours at the time of evaluation for eligibility unless already on extra-corporeal life support 2. Age ≥ 18 years 3. Hypoxemia not primarily attributable to acute heart failure, fluid overload, or pulmonary embolism (PE) PRACTICAL Platform Exclusion Criteria: 1. Extubation is planned or anticipated on the day of screening 2. ICU discharged is planned or anticipated on the day of screening 3. If the patient is moribund and deemed unlikely to survive 24 hours (as determined by the clinical team) 4. If the patient is being transitioned to a fully palliative philosophy of care EXPAND-ECLS Domain Inclusion Criteria: 1. Receiving invasive Endotracheal mechanical ventilation for ≤ 72 hours.5 days 2. Early Moderate-severe hypoxemic respiratory failure with a PaO2/FiO2≤150200 mmHg for at least 6 hours EXPAND-ECLS Domain Exclusion Criteria: 1. Patients over 70 years of age. 2. Currently receiving any form of ECLS (e.g., Venovenous, venoarterial, or hybrid configuration). 3. Chronic hypercapnic respiratory failure defined as PaCO2 \> 60 mmHg in the outpatient setting. 4. Home mechanical ventilation (non-invasive ventilation or via tracheotomy) except for CPAP/BiPAP used solely for sleep-disordered breathing. 5. Actual body weight exceeding 1 kg per centimeter of height. 6. More than 48 hours have passed since meeting inclusion criteria. 7. Severe hypoxemia with PaO2/FiO2 \< 80mmHg for \> 6 hours at time of screening. 8. Severe hypercapnic respiratory failure with pH \< 7.25 and PaCO2 \> 60 mmHg for \> 6 hours at time of screening. 9. Expected mechanical ventilation duration \< 48 hours at time of screening. 10. Confirmed diffuse alveolar hemorrhage from vasculitis. 11. Contraindications to limited anticoagulation (e.g., active GI bleeding, bleeding diathesis). 12. Previous hypersensitivity/anaphylactic reaction to heparin or heparin-induced thrombocytopenia 13. Neurologic conditions at risk for or undergoing treatment for intracranial hypertension 14. Underlying illness with life expectancy \< 1 year 15. Pregnancy (due to unknown effects of PaCO2 changes on placental blood flow) 16. Respiratory failure known or suspected to be caused by COVID-19. IMV Domain Inclusion Criteria: 1. Intubated patients, not on ECLS, with low normalized respiratory elastance (\<2.5 cm H2O/(ml/kg predicted body weight)) at the time of eligibility assessment OR 2. Intubated patients, not on ECLS, with high normalized respiratory system elastance (≥2.5 cm H2O/(ml/kg predicted body weight)) at the time of eligibility assessment OR 3. FOR STUDY SITES PARTICIPATING IN THE LDPVS INTERVENTION: Patient is on ECLS at the time of eligibility assessment. Note: Patients in this state are only eligible for the LPV or LDPVS intervention 4. FOR STUDY SITES PARTICPATING IN THE EIT INTERVENTION: PaO2/FiO2 (if available) \< 200 mm Hg at randomization. If PaO2/FiO2 has not been measured, SpO2 = 97% on FiO2 =60%. IMV Domain Exclusion Criteria: 1. PaO2/FiO2 \>300 mm Hg or (S/F \>250, if PaO2/FiO2 has not been measured) at the time of randomization 2. Chronic hypercapnic respiratory failure defined as PaCO2\>60mmHg in the outpatient setting 3. Home mechanical ventilation (non-invasive ventilation or via tracheotomy), not including nocturnal CPAP applied by nasal or face mask or home tracheotomy if not ventilated 4. Severe hypoxemia with PaO2/FiO2\<80mmHg for \>6 consecutive hours at the time of randomization 5. Severe hypercapnic respiratory failure with pH\<7.25 and PaCO2\>60mmHg for \>6 consecutive hours at the time of randomization 6. Anticipated duration of mechanical ventilation is \<48 hours from the time of screening 7. Duration of mechanical ventilation during current ICU admission is \>72 hours 8. Previously diagnosed neuromuscular disorder 9. Current diagnosis of severe acute brain injury (e.g. ischemic or hemorrhagic stroke, traumatic brain injury) with Glasgow Coma Scale ≤ 8 10. Baseline weight prior to or at hospital admission less than 35 kilograms 11. Receiving extracorporeal life support without continuous invasive mechanical ventilatory support CORT-E2 Domain Early Cohort Inclusion Criteria 1. Within 72 hours of admission to an ICU 2. New unilateral or bilateral airspace disease CORT-E2 Domain Early Domain Exclusion Criteria 1. Receiving only low flow oxygen therapy less than or equal to 15L/min 2. Corticosteroid use during the 14 days prior to screening 3. Existing indication for corticosteroids 4. High suspicion for/or confirmed COVID infection 5. Acute traumatic brain injury during the index hospital admission 6. Allergy to dexamethasone CORT-E2 Domain Extended Cohort Inclusion Criteria 1. Are admitted to an ICU 2. Have already received 10 days of corticosteroid specifically for acute respiratory failure, this will include patients: (a) randomized to corticosteroid arm in Early Cohort, (b) patients with COVID receiving corticosteroids as standard of care , (c) and others who have received corticosteroids for AHRF 3. Ongoing AHRF requiring HFNC, NIV (continuous positive airway pressure \[CPAP\] or bilevel) or invasive ventilation CORT-E2 Domain Extended Cohort Exclusion Criteria 1. An alternate indication for ongoing corticosteroids 2. Acute traumatic brain injury this hospital admission FLUDRO Domain Inclusion Criteria 1. Within 72 hours of admission to an ICU FLUDRO Domain Exclusion Criteria 1. Known hypersensitivity to fludrocortisone 2. An inability to receive fludrocortisone due to lack of enteral access 3. An indication to prescribe fludrocortisone for a reason that is unrelated to a current episode of pneumonia or acute respiratory failure, such as Addison's disease 4. Belief of the treating clinical team that study participation would not be in the best interest of the patient FAST-3 Domain Inclusion Criteria (must meet all 3 of the following) 1. Patient is in a PRACTICAL eligible platform state and requires advanced respiratory support (ARS) defined as one of the following: a. Invasive mechanical ventilation with FiO2 \> 40% b. Non-Invasive Ventilation (\> 4 hours consecutively with FiO2 \> 40%) defined as: i. CPAP or BiPAP (any settings or interface) ii. HFNC (flow \> 40 liter per minute) 2. PaO2/FiO2 \< 300 mm Hg or SpO2/FiO2 \< 315 (if PaO2/FiO2 unavailable due to lack of arterial blood gas at the time of screening). For SpO2/FiO2, criteria are SpO2 ≤ 97% on FiO2 ≥ 40% on both of the 2 hours immediately preceding eligibility assessment. If an arterial blood gas can be obtained, then a PaO2/FiO2 ratio is preferable. 3. Patient commenced advanced respiratory support \< 48 hours prior to randomization. FAST-3 Domain Exclusion Criteria 1. Patient commenced advanced respiratory support \> 48 hours to time of randomization. 2. Known history of severe chronic pulmonary disease e.g., pre-infection requirement for home oxygen therapy or presence of chronic hypercapnia (PaCO2 \> 60 mmHg); mild - moderate disease is still eligible in the absence of chronic hypercapnia or need for chronic oxygen therapy. 3. Currently enrolled in another trial studying investigational anti-inflammatory therapy, excluding established treatments used in clinical practice such as corticosteroids. 4. Known allergy to furosemide or sulfonamide drugs. If the patient is allergic to sulfonamide drugs but has received in the past or is currently receiving furosemide without incident, they can be enrolled since cross-reactivity between furosemide and sulfonamide agents is rare. ESCAPE Domain Inclusion Criteria 1. Patients with severe AHRF who have an underlying immunocompromised condition 2. Within 48 hours of fulfilling the AHRF inclusion criteria as well as PaO2/FiO2 \<300 or a SaO2/FiO2 \< 315 on non-invasive respiratory support (venturi mask, non-invasive ventilation or high flow nasal oxygen as per the FiO2 requirements above) or invasive ventilation. Patients may be enrolled from the wards or ICU. Immunocompromised patients include: 1. Any patients requiring long term (\>30 days) corticosteroids (\>20 mg/day), 2. Any patients receiving non-corticosteroid immunosuppressive medications within the prior 3 months, 3. Acquired or inherited immunodeficiency syndrome, 4. Recipients of solid organ transplant, 5. Active hematologic malignancy (diagnosis or receiving treatment within prior 6 months), 6. Active solid tumor (diagnosis or receiving treatment within the prior 6 months) or 7. Any patients who have undergone allogeneic or autologous hematopoietic cell transplant in the prior 6 months (HCT). ESCAPE Domain Exclusion Criteria 1. Patients whom are deemed palliative. WAVEFORM Domain Inclusion Criteria 1\. Patient is intubated at the time of eligibility assessment. WAVEFORM Domain Exclusion Criteria 1. PaO2/FiO2 \>300 mm Hg or (S/F \>250, if PaO2/FiO2 has not been measured) at the time of eligibility assessment. 2. Duration of mechanical ventilation during current ICU admission is ≥72 hours. 3. Receiving ECLS without continuous invasive mechanical ventilatory support. IMV-ECLS Domain Inclusion Criteria 1\. Patients with AHRF (as defined in platform inclusion criteria #1 above) who have been consented for cannulation for VV-ECLS or who have been initiated on VV-ECLS within 6 hours at the time of randomization IMV-ECLS Domain Exclusion Criteria 1. Patients receiving ECLS for the primary intention of extracorporeal CO2 removal 2. Patients expected to be liberated from ECLS within \<24 hours 3. History of recent pneumothorax or pneumomediastinum (\<3 months at the time of eligibility assessment/randomization) 4. Patients receiving ECLS for the primary intention of bridge to lung transplantation (at the time of eligibility assessment/randomization) IMPROV Domain Inclusion Criteria 1. Patients receiving invasive mechanical ventilation for AHRF as defined by the PRACTICAL platform trial criteria above. 2. Within 7 calendar days of intubation IMPROV Domain Exclusion Criteria 1. Patient is expected to be liberated from mechanical ventilation within 24 hours 2. Known or suspected chronic hypercapnic respiratory failure defined as PaCO2\>60mmHg in the outpatient setting 3. Home mechanical ventilation (non-invasive ventilation or via tracheotomy), not including nocturnal CPAP applied by nasal or face mask or home tracheotomy if not ventilated 4. Known pneumothorax or pneumomediastinum without chest tube placement sustained during current ICU admission\* (re-confirm immediately prior to randomization) 5. Patient is admitted primarily for acute brain injury (stroke, traumatic brain injury, etc.) 6. Previously diagnosed chronic neuromuscular disorder 7. Patient has an implantable cardiac defibrillator or pacemaker 8. Planned to be transferred to another hospital before ICU discharge 9. Already receiving a regimen of inspiratory muscle training using external resistive device or diaphragm neurostimulation

Primary outcome measure(s)

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.
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.
WAVEFORM domain — considering death as a competing event
Duration of mechanical ventilation (MV)

Trial sites (89)

Facility	City	Region	Status
University of Arizona	Tucson	Arizona	Recruiting
University of California Los Angeles (UCLA)	Los Angeles	California	Recruiting
University of San Diego (UCSD)	San Diego	California	Recruiting
University of California San Francisco	San Francisco	California	Recruiting
University of Colorado Hospital	Aurora	Colorado	Recruiting
University of Kentucky	Lexington	Kentucky	Recruiting
University of Maryland Medical System	Baltimore	Maryland	Recruiting
The Johns Hopkins Medicine	Baltimore	Maryland	Recruiting
VA Ann Arbor Healthcare System	Ann Arbor	Michigan	Not Yet Recruiting
University of Michigan Health	Ann Arbor	Michigan	Recruiting
Washington University	St Louis	Missouri	Recruiting
University of Nebraska Medical Center	Omaha	Nebraska	Recruiting
Mount Sinai New York City	New York	New York	Recruiting
Columbia University Irving Medical Center	New York	New York	Recruiting
Wake Forest University School of Medicine	Winston-Salem	North Carolina	Recruiting
University of Cincinnati College of Medicine	Cincinnati	Ohio	Recruiting
Cleveland Clinic	Cleveland	Ohio	Recruiting
Oregon Health & Science University (OHSU)	Portland	Oregon	Recruiting
University of Pennsylvania	Philadelphia	Pennsylvania	Recruiting
Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	Recruiting
University of Pittsburgh Medical Center (UPMC)	Pittsburgh	Pennsylvania	Recruiting
Rhode Island Hospital	Providence	Rhode Island	Recruiting
Medical University of South Carolina (MUSC)	Charleston	South Carolina	Recruiting
Vanderbilt university medical center	Nashville	Tennessee	Recruiting
University of Utah Health	Farmington	Utah	Recruiting
Sentara Health	Norfolk	Virginia	Recruiting
Royal Prince Alfred Hospital	Camperdown	New South Wales	Recruiting
Nepean Hospital	Kingswood	New South Wales	Recruiting
Wollongong Hospital	Wollongong	New South Wales	Recruiting
Flinders Medical Centre	Bedford Park	Southern Adelaide	Recruiting
St Vincents Sydney	Darlinghurst	Sydney	Recruiting
Bendigo Health Victoria	Bendigo	Victoria	Recruiting
University Hospital Geelong	Geelong	Victoria	Recruiting
The Austin Hospital	Heidelberg	Victoria	Recruiting
University of Calgary	Calgary	Alberta	Recruiting
University of Alberta/Edmonton University Hospital	Edmonton	Alberta	Recruiting
Nanaimo Regional General Hospital	Nanaimo	British Columbia	Recruiting
Surrey Memorial Hospital	Surrey	British Columbia	Recruiting
St. Paul's Hospital	Vancouver	British Columbia	Recruiting
Royal Jubilee Hospital	Victoria	British Columbia	Recruiting

+ 49 more sites — see the full list on the official registry below.

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