Clinical trial NCT02447692: Proportional Assist Ventilation for Minimizing the Duration of Mechanical Ventilation: The PROMIZING Study
Official title: Proportional Assist Ventilation for Minimizing the Duration of Mechanical Ventilation: The PROMIZING Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Critically Ill
Acute Respiratory Failure
Keywords: Proportional Assist Ventilation
Pressure Support Ventilation
Weaning
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Medtronic
name: Canadian Critical Care Trials Group
First posted: 2015-05-19
Enrollment: 575
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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)?

Detailed description: 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.

Eligibility criteria: 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 hypercapnia (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
* A11. Severe, end-stage, irreversible respiratory or cardiac disease (e.g. interstitial lung disease, pulmonary fibrosis, cardiomyopathy, valvulopathy) likely to result in prolonged or chronic ventilator dependence /unlikely to wean from mechanical ventilation \[Note: patients who are candidates for intervention to treat the underlying respiratory/cardiac disease (e.g. lung transplant, heart transplant, cardiac surgery) may be re-evaluated once intervention is complete and they no longer meet criteria A11.\]

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. Patient has met enrolment inclusion criteria B1-B5 AND 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 (1): 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; Note (2): B9 does not apply to patients on ECMO.)
* B10. Patient transferred to a non-participating centre

B. ENROLMENT DEFERRAL CRITERIA:

* B11. Plan to extubate/discontinue mechanical ventilation within \<24 hours (Reassess within 24 hours)
* B12. Patient currently on ECMO (Reassess patient once off ECMO)
* C9: Plan for surgery or complex procedure that will require full ventilation to be done prior to attempting extubation (e.g. Procedure requiring neuromuscular blockade and/or heavy sedation, such that patient would be apneic, or not be able to trigger ventilator) (Reassess after surgery/procedure complete)

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.

C. 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 (HR\>140 or \<50) with clinical signs of low cardiac output or or SBP\<80 mmHg
* C10. Receiving a "strict lung protective" ventilation strategy for ARDS (eg. Order on chart to keep Vt ≤6 mL/kg PBW)

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 ZERO CPAP Trial OR Fails the SBT

E. RANDOMIZATION EXCLUSION CRITERIA:

* B9. Patient has met enrolment inclusion criteria B1-B5 AND has tolerated pressure support of 0-20 cm H2O or proportional assist ventilation of 0-85% ≥24 consecutive hours (including time on CPAP, t-piece, or tracheostomy mask). Note (1): 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; Note (2): B9 does not apply to patients while on ECMO
* 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)

Primary outcomes:
measure: Time from randomization to successful liberation from invasive mechanical ventilation.
timeFrame: up to 90 days
Secondary outcomes:
measure: Ventilator-free days at 14, 21 and 28 days post randomization
timeFrame: 14, 21 and 28 days post randomization
measure: Time from randomization to live ICU discharge (up to day 90)
timeFrame: up to 90 days
measure: Time from randomization to live hospital discharge (up to day 90)
timeFrame: up to 90 days
measure: Mortality
timeFrame: up to 90 days
measure: Weaning Progress
timeFrame: up to 90 days
measure: Weaning Difficulties
timeFrame: 90 days
measure: Weaning Complications
timeFrame: 90 days
measure: Tolerance of modes
timeFrame: 90 days
measure: Serious Adverse Events
timeFrame: 90 days
Other outcomes:
measure: Co-interventions
timeFrame: 28 days
measure: Subgroup analyses based on: (a) duration of MV prior to randomization as a continuous variable or as a binary variable of greater than 5 days
timeFrame: At randomization
measure: Subgroup analyses based on (b) failing an SBT prior to randomization vs. failed CPAP 0 trial vs. failed weaning criteria prior to randomization
timeFrame: At randomization
measure: Subgroup analyses based on (c) failed extubation prior to randomization
timeFrame: At randomization
measure: Subgroup analyses based on (d) mild vs. moderate vs. severe frailty
timeFrame: At ICU admission
measure: Subgroup analyses based on COVID-19 positive test
timeFrame: At ICU admission
measure: Subgroup analyses based on tracheostomy present at randomization
timeFrame: At randomization
Locations:
city: Buenos Aires
country: Argentina
facility: El Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre - University Hospital
state: Ontario
city: London
country: Canada
facility: Victoria Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Hospital - Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: North York General Hospital
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: UHN- Toronto General Hospital
state: Ontario
city: Toronto
country: Canada
facility: UHN- Toronto Western Hospital
state: Ontario
city: Montréal
country: Canada
facility: Centre hospitalier de l'Université de Montréal (CHUM)
state: Quebec
city: Montréal
country: Canada
facility: Royal Victoria Hospital
state: Quebec
city: Québec
country: Canada
facility: Institut Universitaire de cardiologie et de pneumologie de Quebec
state: Quebec
city: Angers
country: France
facility: Centre Hospitalier Universitaire (CHU) de Angers
city: Créteil
country: France
facility: Centre Hospitalier Intercommunal de Créteil
city: Créteil
country: France
facility: Hôpital Henri Mondor (Assistance Publique-Hôpitaux de Paris)
city: Paris
country: France
facility: Hôpital Universitaire Pitié-Salpêtrière
city: Rouen
country: France
facility: Centre Hospitalier Universitaire (CHU) de Rouen
city: Heraklion
country: Greece
facility: University Hospital of Heraklion
city: Ferrara
country: Italy
facility: University Hospital of Ferrara
city: Turin
country: Italy
facility: San Giovanni Battista University Hospital
city: Riyadh
country: Saudi Arabia
facility: King Abdulaziz Medical City
city: Barcelona
country: Spain
facility: Hospital de Sant Pau
Study officials:
affiliation: London Health Sciences Centre, London, Ontario, Canada
name: Karen J Bosma
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Michael's Hospital, Toronto, Ontario, Canada
name: Laurent Brochard
role: PRINCIPAL_INVESTIGATOR
References: