Proportional Assist Ventilation for Minimizing the Duration of Mechanical Ventilation: The PROMIZING Study
Proportional Assist Ventilation for Minimizing the Duration of Mechanical Ventilation: The PROMIZING Study
For adult patients with acute respiratory failure requiring invasive mechanical ventilation,
 does a ventilation strategy using proportional assist ventilation with load-adjustable gain
 factors (PAV+) result in a shorter duration of time spent on mechanical ventilation than a
 ventilation strategy using pressure support ventilation (PSV)?
Patients with acute respiratory failure require mechanical ventilation to help them breathe
 until they recover from their acute illness. Although mechanical ventilation is necessary to
 sustain life in such situations, it can induce weakness of the respiratory muscles which may
 lead to prolonged dependence on the ventilator. Prolonged dependence on mechanical
 ventilation is associated with increased mortality, morbidity and costs to the healthcare
 system. Thus, a main goal of assisted mechanical ventilation is to reduce the patient's
 respiratory distress while maintaining some respiratory muscle activity. To attain this goal,
 the amount of ventilator assistance should theoretically be adjusted to target normal or
 reasonable levels of respiratory effort.

 Modes of Mechanical Ventilation:

 Proportional assist ventilation with load-adjustable gain factors (PAV+) is a mode of
 mechanical ventilation which delivers assistance to breathe in proportion to the patient's
 effort. The proportional assistance, called the gain, can be adjusted by the clinician to
 maintain the patient's respiratory effort or workload within a reasonable range. This is the
 only mode of ventilation which allows for measurement and targeting of a specific range of
 respiratory muscle activity by the patient.

 Pressure support ventilation (PSV) is a mode of ventilation which is considered the current
 standard of care for assisting breathing of patients during the recovery phase of acute
 respiratory failure. Several studies have shown short term advantages of PAV over PSV,
 including improved patient-ventilator synchronization, improved adaptability to changes in
 patient effort, and improved sleep quality.

 Goal of this Randomized Controlled Trial:

 To demonstrate that for patients with acute respiratory failure, ventilation with PAV+, being
 more physiological, will result in a shorter duration of time spent on mechanical ventilation
 than ventilation with PSV.
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)