Phase
Condition
Lung Injury
Respiratory Failure
Treatment
PEEP-AOP
PEEP-10
Lung- and Diaphragm-Protective Ventilation and Sedation (LDPVS)
Clinical Study ID
Ages > 18 All Genders
Study Summary
Eligibility Criteria
Inclusion
PRACTICAL Platform Inclusion Criteria:
Acute hypoxemic respiratory failure meeting all of the following criteria;
New or worsening respiratory symptoms developing within 2 weeks prior to theonset of need for oxygen or respiratory support
Receiving any of the following types of oxygen or respiratory support for atleast 4 hours prior to the time of randomization; supplemental oxygen at 10L/min or higher, high flow nasal oxygen (at any flow rate), invasive ventilatorsupport, extra-corporeal life support (ECLS), or non-invasive ventilatorsupport
Minimum FiO2 ≥ 0.40 (for venturi mask, high flow nasal cannula, or invasive ornon-invasive ventilation) or oxygen flow rate ≥10 L/min on face mask for atleast 4 hours at the time of evaluation for eligibility unless already onextra- corporeal life support
Age ≥ 18 years
Hypoxemia not primarily attributable to acute heart failure, fluid overload, orpulmonary embolism (PE)
Exclusion
PRACTICAL Platform Exclusion Criteria:
Extubation is planned or anticipated on the day of screening
ICU discharged is planned or anticipated on the day of screening
If the patient is moribund and deemed unlikely to survive 24 hours (as determined bythe clinical team)
If the patient is being transitioned to a fully palliative philosophy of care
ULTIMATE Domain Inclusion Criteria:
Endotracheal mechanical ventilation for ≤5 days
Early moderate-severe hypoxemic respiratory failure with a PaO2/FiO2≤200 mmHg for atleast 6 hours
ULTIMATE Domain Exclusion Criteria:
Patients over 65 years of age
Currently receiving any form of ECMO (ex. venovenous, venoarterial, or hybridconfiguration)
Δ PL-dyn ≤20 or Static Δ P≤15 cm H2O while receiving VT 6mL/kg (i.e. normalizedelastance ≤ 2.5 cmH2O/mL/kg)
Chronic hypercapnic respiratory failure defined as PaCO2>60mmHg in the outpatientsetting
Home mechanical ventilation (non-invasive ventilation or via tracheotomy), not CPAP
Actual body weight exceeding 1kg per centimeter of height
More than 48 hours have passed since meeting inclusion criteria
Severe hypoxemia with PaO2/FiO2<80mmHg for >6 hours at time of screening
Severe hypercapnic respiratory failure with pH<7.25 and PaCO2>60mmHg for >6 hours attime of screening
Expected mechanical ventilation duration <48 hours at time of screening
Confirmed diffuse alveolar hemorrhage from vasculitis
Contraindications to limited anticoagulation (ex. active GI bleeding, bleedingdiathesis)
Pregnancy-due to unknown effects of PaCO2 changes on placental blood flow
Respiratory Failure known or suspected to be caused by COVID-19
IMV Domain Inclusion Criteria:
Intubated patients, not on ECLS, with low normalized respiratory elastance (<2.5 cmH2O/(ml/kg predicted body weight)) at the time of eligibility assessment OR
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
FOR STUDY SITES PARTICIPATING IN THE LDPVS INTERVENTION: Patient is on ECLS at thetime of eligibility assessment. Note: Patients in this state are only eligible forthe LPV or LDPVS intervention
IMV Domain Exclusion Criteria:
PaO2/FiO2 >300 mm Hg or (S/F >250, if PaO2/FiO2 has not been measured) at the timeof randomization
Chronic hypercapnic respiratory failure defined as PaCO2>60mmHg in the outpatientsetting
Home mechanical ventilation (non-invasive ventilation or via tracheotomy), notincluding nocturnal CPAP applied by nasal or face mask or home tracheotomy if notventilated
Severe hypoxemia with PaO2/FiO2<80mmHg for >6 consecutive hours at the time ofrandomization
Severe hypercapnic respiratory failure with pH<7.25 and PaCO2>60mmHg for >6consecutive hours at the time of randomization
Anticipated duration of mechanical ventilation is <48 hours from the time ofscreening
Duration of mechanical ventilation during current ICU admission is >72 hours
Previously diagnosed neuromuscular disorder
Current diagnosis of severe acute brain injury (e.g. ischemic or hemorrhagic stroke,traumatic brain injury) with Glasgow Coma Scale ≤ 8
Baseline weight prior to or at hospital admission less than 35 kilograms
Receiving extracorporeal life support without continuous invasive mechanicalventilatory support
CORT-E2 Domain Early Cohort Inclusion Criteria
Within 72 hours of admission to an ICU
New unilateral or bilateral airspace disease
CORT-E2 Domain Early Domain Exclusion Criteria
Receiving only low flow oxygen therapy less than or equal to 15L/min
Corticosteroid use during the 14 days prior to screening
Existing indication for corticosteroids
High suspicion for/or confirmed COVID infection
Acute traumatic brain injury during the index hospital admission
Allergy to dexamethasone
CORT-E2 Domain Extended Cohort Inclusion Criteria
Are admitted to an ICU
Have already received 10 days of corticosteroid specifically for acute respiratoryfailure, this will include patients: (a) randomized to corticosteroid arm in EarlyCohort, (b) patients with COVID receiving corticosteroids as standard of care , (c)and others who have received corticosteroids for AHRF
Ongoing AHRF requiring HFNC, NIV (continuous positive airway pressure [CPAP] orbilevel) or invasive ventilation
CORT-E2 Domain Extended Cohort Exclusion Criteria
An alternate indication for ongoing corticosteroids
Acute traumatic brain injury this hospital admission
Study Design
Study Description
Connect with a study center
University Health Network
Toronto,
CanadaActive - Recruiting
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