Eligibility Details:
A staged enrolment process will be used to identify patients eligible to be enrolled and
randomized in the study. At each stage of the enrolment process, a patient must meet
inclusion criteria and not meet exclusion criteria in order to pass. To progress to the
next stage, patients must continue to pass criteria from the prior stages. After enrolment,
there are also specific tests to perform (with pass/fail criteria) to determine eligibility
to be randomized.
A. SCREENING INCLUSION CRITERIA:
- A1. Age 18 years or older
- A2. Intubated and receiving any mode of invasive mechanical ventilation ≥ 24 hours
A. SCREENING EXCLUSION CRITERIA:
- A3. Anticipating withdrawal of life support and/or shift to palliation as the goal of
care
- A4. Severe central neurologic disorder (eg. Hemorrhage, stroke, tumour) causing
elevated intracranial pressure, or impaired control of breathing, or requiring
specific ventilator adjustments (i.e. To attain specific CO2 target) or requiring
neurosurgical intervention
- A5. Known or suspected severe or progressive neuromuscular disorder likely to result
in prolonged or chronic ventilator dependence (eg. Guillain-Barré syndrome, Myasthenia
Gravis, ALS, MS, high spinal cord injury, kyphoscoliosis or other restrictive
disorder) (Note that obesity hypoventilation syndrome that may be managed with
nocturnal non-invasive ventilation is NOT an exclusion under A5)
- A6. Severe COPD: Baseline daytime hypercapnea (pCO2> 50 mmHg) OR GOLD 4 airflow
limitation (FEV1<30% predicted) OR MRC class 4 symptoms ("I am too breathless to leave
the house" OR "I am breathless when dressing")
- A7. Broncho-pleural fistula
- A8. Tracheostomy present at ICU admission for the purpose of chronic or prolonged
mechanical ventilation (>21 days). (Note that a patient who was endotracheally
intubated for acute respiratory failure and received a tracheostomy during their ICU
admission, prior to enrolment, is not excluded under A8).
- A9. Current enrolment in a confounding study, as assessed by the steering committee
- A10. Previous randomization in the PROMIZING Study
B. ENROLMENT INCLUSION CRITERIA:
- B1. Ability or potential ability to trigger ventilator breaths (i.e. not receiving
neuromuscular blockade).
- B2. On Assist/Control volume-cycled ventilation: Technically satisfactory plateau
pressure ≤ 30 cm H2O (see Operations Manual)OR On Assist/Control pressure-controlled
ventilation or similar mode: Pressure control plus PEEP ≤ 30 cm H2O OR On Pressure
Support ventilation: Pressure support plus PEEP ≤ 30 cm H2O OR On Proportional Assist
ventilation: PAV gain <85%
- B3. PaO2 ≥ 60 mmHg or SpO2 ≥ 90% on FiO2 ≤ 0.60 and PEEP ≤ 15 cm H2O
- B4. Metabolic disorders corrected: pH ≥7.32
- B5. Stable hemodynamic status: stable or decreasing doses of vasopressors for ≥6 hours
- B6. Anticipate ongoing need for ventilation >24 hours
B. ENROLMENT EXCLUSION CRITERIA:
- B7. Extubated
- B8. Died
- B9. Has tolerated pressure support of 0-20 cm H2O or proportional assist ventilation
of 0-85% for ≥24 consecutive hours (including time on CPAP, t-piece, or tracheostomy
mask). (Note that it is acceptable to include a patient who has been tried on pressure
support or proportional assist ventilation but has required pressures >20 cmH2O or
assistance >85% or has required return to A/C ventilation within the 24 hour time
window.)
- B10. Patient transferred to a non-participating centre
- E3. Passed SBT on t-piece*, FiO2 0.40 for 30-120 minutes *for the purposes of this
study, the Sponsor considers SBT performed with patients connected to ventilator on
flow-by with CPAP of 0 cmH2O and FiO2 0.40 to be equivalent to SBT performed on
T-piece with FiO2 0.40.
B. ENROLMENT DEFERRAL CRITERIA:
• B11. Plan to extubate/discontinue mechanical ventilation within <24 hours
C. PRESSURE SUPPORT TRIAL INCLUSION CRITEIRA:
- C2. Upon review of Screening and Enrolment criteria (A and B), the patient still
passes.
- C3. Treating physician has provided verbal consent to proceed with standardized tests
and randomization if eligibility criteria are met.
D. PRESSURE SUPPORT TRIAL DEFERRAL CRITERIA:
- C6. High dose vasopressor requirements (i.e. epinephrine or norepinephrine >0.5
ug/kg/min or equivalent) OR patient requiring an increase in dose of vasopressor
within 6 hrs
- C7. Active cardiac ischemia (dynamic ST changes on monitor or ECG within 6 hours)
- C8. Unstable arrhythmias with HR>140 or SBP<90 mmHg
- C9. Plan for surgery or complex procedure that will require full ventilation to be
done within 24 hrs (eg. Procedure requiring neuromuscular blockade and/or heavy
sedation, such that patient would be apneic, or not be able to trigger ventilator)
- C10. Receiving a "strict lung protective" ventilation strategy for ARDS (eg. Order on
chart to keep Vt ≤6 mL/kg PBW)
- C11. Inability to trigger breaths/apnea (Note that for patients on A/C, if every
breath is a controlled breath, the treating clinician will need to temporarily
decrease the A/C rate to determine if patients are able to trigger ventilator breaths.
C. PRESSURE SUPPORT TRIAL EXCLUSION CRITERIA:
• C12. Treating physician has declined consent
D. WEANING CRITERIA:
- D1. SpO2≥ 90% on FiO2 ≤0.40 and PEEP ≤8 cmH2O
- D2. pH ≥7.32
- D3. Vasopressor requirements no higher than norepinephrine 0.1 ug/kg/min or
equivalent.
In the final stage (E), patients will be considered eligible for randomization if the
following criteria are met.
E. RANDOMIZATION INCLUSION CRITERIA:
- C1. Patient/SDM has provided consent OR Plan to obtain deferred consent as Patient
incapable and no SDM available to provide consent within the randomization window
- E1. Upon review of Criteria A, B, and C, the patient still passes and the patient has
passed the PST.
- E2. Does not meet Weaning Criteria OR Fails the CPAP Trial OR Fails the SBT
E. RANDOMIZATION EXCLUSION CRITERIA:
- C4. Patient/SDM has declined consent
- C5. Patient incapable and no SDM available to provide consent (not applicable if plan
to obtain deferred consent)
- E3. Passed SBT on t-piece, FiO2 0.40 for 30-120 minutes
- E4. Approval withdrawn (by physician or patient/SDM)
common.study.methods.has-drugs-no
common.study.methods.is-healthy-yes
