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

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ClinicalTrials.gov Identifier: NCT02447692
Recruitment Status : Recruiting
First Posted : May 19, 2015
Last Update Posted : April 5, 2018
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
Medtronic
Canadian Critical Care Trials Group
Information provided by (Responsible Party):
Karen Bosma, Lawson Health Research Institute

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)?

Condition or disease Intervention/treatment Phase
Critically Ill Acute Respiratory Failure Other: PSV ventilation strategy Other: PAV+ ventilation strategy Not Applicable

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 512 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Proportional Assist Ventilation for Minimizing the Duration of Mechanical Ventilation: The PROMIZING Study
Actual Study Start Date : September 14, 2016
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : December 2019


Arm Intervention/treatment
Active Comparator: PSV ventilation strategy
The control is the standard of care PSV ventilation strategy, designed to adjust the level of support according to usual clinical parameters.
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

Active Comparator: PAV+ ventilation strategy
The intervention is a PAV+ ventilation strategy, designed to adjust the level of support (gain) to target a predefined range of respiratory muscle pressure.
Other: 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




Primary Outcome Measures :
  1. Ventilator Free Days (VFDs) at 21 days post randomization [ Time Frame: 21 days ]
    "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.


Secondary Outcome Measures :
  1. Ventilator-free days at 14 and 28 days post randomization [ Time Frame: 14 and 28 days post randomization ]
  2. Time from randomization to successful extubation [ Time Frame: up to 90 days ]
  3. Time from randomization to live ICU discharge [ Time Frame: up to 90 days ]
  4. Time from randomization to live hospital discharge [ Time Frame: up to 90 days ]
  5. Mortality measured as ICU mortality, hospital mortality, 14, 21, 28 and 90 day mortality [ Time Frame: up to 90 days ]
  6. Weaning Progress [ Time Frame: 90 days ]
    Weaning Progress, measured as time from randomization to first SBT, first successful SBT, and first extubation

  7. Difficult Weaning [ Time Frame: 90 days ]
    Weaning Difficulties, measured as the number of patients failing first SBT or first extubation attempt and requiring up to 7 days to CONFIDENTIAL Study Protocol Version 4.0 - 20JUNE2017 Page 9 of 54 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)

  8. Weaning Complications [ Time Frame: 90 days ]
    Weaning Complications, measured as the number of patients requiring: non-invasive ventilation post-extubation, ventilated more than 7 days post randomization, receiving tracheostomy post-randomization, requiring reintubation (up to 7 days after planned extubation)

  9. Tolerance of Modes [ Time Frame: 90 days ]
    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

  10. Cumulative doses of narcotics [ Time Frame: 90 days ]
    Cumulative dose of narcotics (converted to morphine equivalents); benzodiazepines (converted to midazolam equivalents); propofol, and dexmedetomidine

  11. Number of patients receiving any antipsychotic medication [ Time Frame: 90 days ]
  12. Sensitivity analyses of primary and secondary outcomes defining "successful extubation" as "48 hours without reintubation" [ Time Frame: 90 days ]
  13. Sensitivity analyses of primary and secondary outcomes assigning a value of 0 ventilator-free days to any participant who dies at any time during the study period [ Time Frame: 90 days ]

Other Outcome Measures:
  1. Subgroup analyses based on: (a) duration of MV prior to randomization greater than 5 days [ Time Frame: 90 days ]
    Identifies a subgroup of patients at time of randomization who are at risk for prolonged weaning

  2. Subgroup analyses based on (b) failing an SBT prior to randomization [ Time Frame: 90 days ]
    Identifies a subgroup of patients at time of randomization classified as having "difficult weaning".

  3. Subgroup analyses based on (c) failed extubation prior to randomization [ Time Frame: 90 days ]
    Identifies a subgroup of patients at time of randomization classified as having "difficult weaning".



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02447692


Contacts
Contact: Shristi Bhatia 416-864-6060 ext 77049 BhatiaSh@smh.ca
Contact: Karen J Bosma 519-663-3531 KarenJ.Bosma@lhsc.on.ca

Locations
Canada, British Columbia
Royal Columbian Hospital Not yet recruiting
New Westminster, British Columbia, Canada
Contact: Steven Reynolds       steven.reynolds@fraserhealth.ca   
Principal Investigator: Steven Reynolds         
Canada, Ontario
London Health Sciences Centre - University Hospital Recruiting
London, Ontario, Canada, N6A 5A5
Contact: K.J. Bosma    519-663-3531    karenj.bosma@lhsc.on.ca   
Contact: Tracey Bentall    519-685-8500 ext 32546    traceyc.bentall@lhsc.on.ca   
Principal Investigator: Karen J. Bosma         
Victoria Hospital Recruiting
London, Ontario, Canada
Contact: Claudio Martin       claudio.martin@lhsc.on.ca   
Contact: Eileen Campbell       Eileen.Campbell@lhsc.on.ca   
Principal Investigator: Claudio Martin         
Mount Sinai Hospital Not yet recruiting
Toronto, Ontario, Canada
Contact: Sangeeta Mehta       geeta.Mehta@sinaihealthsystem.ca   
Contact: Sumesh Shah       sumesh.shah@sinaihealthsystem.ca   
Principal Investigator: Sangeeta Mehta         
St. Michael's Hospital Recruiting
Toronto, Ontario, Canada
Contact: Laurent Brochard       brochardl@smh.ca   
Contact: Thomas Piraino       pirainot@smh.ca   
Principal Investigator: Karen Burns         
Principal Investigator: Laurent Brochard         
UHN- Toronto General Hospital Not yet recruiting
Toronto, Ontario, Canada
Contact: Niall Ferguson       Niall.Ferguson@uhn.ca   
UHN- Toronto Western Hospital Not yet recruiting
Toronto, Ontario, Canada
Contact: Niall Ferguson       Niall.Ferguson@uhn.ca   
Canada, Quebec
Hôpital du Sacré-Cœur de Montréal Recruiting
Montréal, Quebec, Canada
Contact: Emmanuel Charbonney       emmanuel.charbonney@umontreal.ca   
Contact: Virginie Williams       eresi@crhsc.rtss.qc.ca   
Principal Investigator: Emmanuel Charbonney         
Institut Universitaire de cardiologie et de pneumologie de Quebec Recruiting
Québec, Quebec, Canada
Contact: Francois Lellouche       francois.lellouche@criucpq.ulaval.ca   
Contact: Pierre-Alexandre Bouchard       pierre-alexandre.bouchard@criucpq.ulaval.ca   
Principal Investigator: Francois Lellouche         
France
Centre Hospitalier Universitaire (CHU) de Angers Recruiting
Angers, France
Contact: Alain Mercat       alain.mercat@univ-angers.fr   
Contact: Laure Masson       lamasson@chu-angers.fr   
Principal Investigator: Alain Mercat         
Hôpital Henri Mondor (Assistance Publique-Hôpitaux de Paris) Recruiting
Créteil, France
Contact: Guillaume Carteaux       guillaume.carteaux@aphp.fr   
Principal Investigator: Guillaume Carteaux         
Centre Hospitalier Universitaire (CHU) de Nice Not yet recruiting
Nice, France
Contact: Jean Dellamonica       dellamonica.j@chu-nice.fr   
Principal Investigator: Jean Dellamonica         
Centre Hospitalier Universitaire (CHU) de Rouen Not yet recruiting
Rouen, France
Contact: Gaetan Beduneau       gaetan.beduneau@chu-rouen.fr   
Principal Investigator: Gaetan Beduneau         
Italy
San Giovanni Battista University Hospital Not yet recruiting
Turin, Italy
Contact: Vito Faneilli       vito.fanelli@unito.it   
Principal Investigator: Vito Fanelli         
Spain
Hospital de Sant Pau Recruiting
Barcelona, Spain
Contact: Juan Carlos Suarez Montero       jsuarez@santpau.cat   
Principal Investigator: Juan Carlos Suarez Montero         
Principal Investigator: Jordi Mancebo         
Sponsors and Collaborators
Lawson Health Research Institute
Canadian Institutes of Health Research (CIHR)
Medtronic
Canadian Critical Care Trials Group
Investigators
Principal Investigator: Karen J Bosma London Health Sciences Centre, London, Ontario, Canada
Principal Investigator: Laurent Brochard St. Michael's Hospital, Toronto, Ontario, Canada

Responsible Party: Karen Bosma, Dr. Karen J. Bosma, Lawson Health Research Institute
ClinicalTrials.gov Identifier: NCT02447692     History of Changes
Other Study ID Numbers: IPR-327433, ISR-2014-10481
First Posted: May 19, 2015    Key Record Dates
Last Update Posted: April 5, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Karen Bosma, Lawson Health Research Institute:
Proportional Assist Ventilation
Pressure Support Ventilation
Weaning

Additional relevant MeSH terms:
Critical Illness
Respiratory Insufficiency
Respiratory Distress Syndrome, Adult
Disease Attributes
Pathologic Processes
Respiration Disorders
Respiratory Tract Diseases
Lung Diseases