Platform of Randomized Adaptive Clinical Trials in Critical Illness (PRACTICAL)
Respiratory Insufficiency, Extracorporeal Membrane Oxygenation Complication, Mechanical Ventilation Pressure High
About this trial
This is an interventional treatment trial for Respiratory Insufficiency
Eligibility Criteria
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 the onset of need for oxygen or respiratory support
- Receiving any of the following types of oxygen or respiratory support for at least 4 hours prior to the time of randomization; supplemental oxygen at 10 L/min or higher, high flow nasal oxygen (at any flow rate), invasive ventilator support, extra-corporeal life support (ECLS), or non-invasive ventilator support
- Minimum FiO2 ≥ 0.40 (for venturi mask, high flow nasal cannula, or invasive or non-invasive ventilation) or oxygen flow rate ≥10 L/min on face mask for at least 4 hours at the time of evaluation for eligibility unless already on extra- corporeal life support
- Age ≥ 18 years
- Hypoxemia not primarily attributable to acute heart failure, fluid overload, or pulmonary embolism (PE)
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 by the 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 at least 6 hours
ULTIMATE Domain Exclusion Criteria:
- Patients over 65 years of age
- Currently receiving any form of ECMO (ex. venovenous, venoarterial, or hybrid configuration)
- Δ PL-dyn ≤20 or Static Δ P≤15 cm H2O while receiving VT 6mL/kg (i.e. normalized elastance ≤ 2.5 cmH2O/mL/kg)
- Chronic hypercapnic respiratory failure defined as PaCO2>60mmHg in the outpatient setting
- 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 at time 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, bleeding diathesis)
- Pregnancy-due to unknown effects of PaCO2 changes on placental blood flow
- Respiratory Failure known or suspected to be caused by COVID-19
Sites / Locations
- University Health NetworkRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Other
Other
Other
Ultra-protective ventilation facilitated by extracorporeal carbon dioxide removal (ULTIMATE) domain
Invasive Mechanical Ventilation (IMV) Strategies domain
The Corticosteroid Early and Extended (CORT-E2) Randomized Controlled Trial domain
Patients with acute hypoxemic respiratory failure in the high elastance state will be randomized to ultra-protective ventilation facilitated by extracorporeal carbon dioxide removal or to conventional lung-protective ventilation.
Patients on invasive mechanical ventilation in the low elastance, high elastance, and ECLS states will be randomized to one of two or three 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 arms.
Patients with acute hypoxemic respiratory failure (AHRF) requiring invasive or non-invasive respiratory support will be randomized in the Early Cohort to receive corticosteroid or usual care without corticosteroids. Patients treated with corticosteroids who still require invasive or non-invasive respiratory support after 10 days will be randomized in the Extended Cohort to extending corticosteroid use or stopping corticosteroids after 10 days.