Proportional Assist Ventilation for Minimizing the Duration of Mechanical Ventilation: The PROMIZING Study

Acute Respiratory Failure Clinical Trial

— PROMIZING  

Official title:

Proportional Assist Ventilation for Minimizing the Duration of Mechanical Ventilation: The PROMIZING Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02447692
• Other study ID #: IPR-327433, ISR-2014-10481
• Status: Completed
• Phase: N/A
• Start date: September 14, 2016
• Est. completion date: September 12, 2023

Study information

• Verified date: May 2024
• Source: Lawson Health Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)?

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 575
• Est. completion date: September 12, 2023
• Est. primary completion date: September 12, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Acute Respiratory Failure
• Critical Illness
• Critically Ill
• Respiratory Insufficiency

Intervention

Other:
• PSV ventilation strategy
An algorithm for adjusting the level of pressure support according to usual clinical parameters; patients not tolerating PSV will be switched to Assist/Control mode according to predefined criteria
• PAV+ ventilation strategy
An algorithm for adjusting the level of support (gain) to maintain a predefined range of respiratory muscle pressure; patients not tolerating PAV+ (Puritan Bennett™ 840 or 980 ventilator) will be switched to Assist/Control mode according to predefined criteria

Locations

Country	Name	City	State
Argentina	El Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"	Buenos Aires
Canada	Kingston General Hospital	Kingston	Ontario
Canada	London Health Sciences Centre - University Hospital	London	Ontario
Canada	Victoria Hospital	London	Ontario
Canada	Centre hospitalier de l'Université de Montréal (CHUM)	Montréal	Quebec
Canada	Royal Victoria Hospital	Montréal	Quebec
Canada	Institut Universitaire de cardiologie et de pneumologie de Quebec	Québec	Quebec
Canada	North York General Hospital	Toronto	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Sunnybrook Hospital - Health Sciences Centre	Toronto	Ontario
Canada	UHN- Toronto General Hospital	Toronto	Ontario
Canada	UHN- Toronto Western Hospital	Toronto	Ontario
France	Centre Hospitalier Universitaire (CHU) de Angers	Angers
France	Centre Hospitalier Intercommunal de Créteil	Créteil
France	Hôpital Henri Mondor (Assistance Publique-Hôpitaux de Paris)	Créteil
France	Hôpital Universitaire Pitié-Salpêtrière	Paris
France	Centre Hospitalier Universitaire (CHU) de Rouen	Rouen
Greece	University Hospital of Heraklion	Heraklion
Italy	University Hospital of Ferrara	Ferrara
Italy	San Giovanni Battista University Hospital	Turin
Saudi Arabia	King Abdulaziz Medical City	Riyadh
Spain	Hospital de Sant Pau	Barcelona

Sponsors (4)

Lead Sponsor	Collaborator
Lawson Health Research Institute	Canadian Critical Care Trials Group, Canadian Institutes of Health Research (CIHR), Medtronic

Countries where clinical trial is conducted

Argentina,  Canada,  France,  Greece,  Italy,  Saudi Arabia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Co-interventions	Co-interventions will be monitored and described including use of sedating medications	28 days
Other	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	Identifies a subgroup of patients at time of randomization who are at risk for prolonged weaning	At randomization
Other	Subgroup analyses based on (b) failing an SBT prior to randomization vs. failed CPAP 0 trial vs. failed weaning criteria prior to randomization	Identifies a subgroup of patients at time of randomization classified as difficult weaning vs. failed CPAP 0 trial vs. failed weaning criteria prior to randomization	At randomization
Other	Subgroup analyses based on (c) failed extubation prior to randomization	Identifies a subgroup of patients at time of randomization classified as having "difficult weaning".	At randomization
Other	Subgroup analyses based on (d) mild vs. moderate vs. severe frailty	Differentiates between severely frail and less frail	At ICU admission
Other	Subgroup analyses based on COVID-19 positive test	Differentiates between COVID-19 positive and COVID-19 negative	At ICU admission
Other	Subgroup analyses based on tracheostomy present at randomization	Identifies a subgroup of patients at risk of prolonged weaning	At randomization
Primary	Time from randomization to successful liberation from invasive mechanical ventilation.	"Successful liberation" is defined as removal of the endotracheal tube AND remaining alive with no need for reintubation/reinstitution of invasive mechanical ventilation for 7 days post extubation, or until successful ICU discharge, or until live hospital discharge, whichever comes first.	up to 90 days
Secondary	Ventilator-free days at 14, 21 and 28 days post randomization	"Ventilator-free days" (VFDs) are defined as the number of days alive and free of INVASIVE ventilation post SUCCESSFUL EXTUBATION or post successful termination of invasive mechanical ventilation (MV) from time of randomization to day 21 post randomization. "Successful extubation" is defined as removal of the endotracheal tube AND remaining alive with no need for reintubation/reinstitution of invasive mechanical ventilation for 7 days post extubation, or until successful ICU discharge, or until live hospital discharge, whichever comes first.	14, 21 and 28 days post randomization
Secondary	Time from randomization to live ICU discharge (up to day 90)	Patients will remain in the study and will continue on the assigned ventilation strategy until: successful extubation, successful ICU discharge, live hospital discharge, death, or 90 days post randomization, whichever comes first.	up to 90 days
Secondary	Time from randomization to live hospital discharge (up to day 90)	Patients will remain in the study and will continue on the assigned ventilation strategy until: successful extubation, successful ICU discharge, live hospital discharge, death, or 90 days post randomization, whichever comes first.	up to 90 days
Secondary	Mortality	Measured as time to death, ICU mortality; hospital mortality; 21, 28, and 90 day mortality	up to 90 days
Secondary	Weaning Progress	Measured as time from randomization to: first SBT; first successful SBT; first extubation	up to 90 days
Secondary	Weaning Difficulties	Measured as the number of patients failing first SBT or first extubation attempt and requiring up to 7 days to extubate (difficult weaning group/group 2); failing first SBT or first extubation attempt and requiring more than 7 days to extubate (prolonged weaning group/group 3)	90 days
Secondary	Weaning Complications	Measured as the number of patients: requiring non-invasive ventilation post-extubation; ventilated more than 7 days post randomization, ventilated more than 21 days from time of intubation (prolonged MV group); receiving tracheostomy post-randomization, requiring re-intubation (up to 7d after planned extubation)	90 days
Secondary	Tolerance of modes	Measured as number of patients ever requiring A/C mode post randomization; number of patient-days requiring A/C mode post randomization	90 days
Secondary	Serious Adverse Events	Incidence of reported serious adverse events	90 days