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

NCT ID: NCT02447692

Last Updated: 2025-05-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 575 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-14
• Study Completion Date: 2024-07-16

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.

Conditions

Critically Ill; Acute Respiratory Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

PSV ventilation strategy

Intervention Type: OTHER

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

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

Group Type: ACTIVE_COMPARATOR

PAV+ ventilation strategy

Intervention Type: OTHER

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

Interventions

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

Intervention Type: 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

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• A1. Age 18 years or older
• A2. Intubated and receiving any mode of invasive mechanical ventilation ≥ 24 hours

• 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

• 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)

• 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

• 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)

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.]

• B7. Extubated
• B8. Died

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Medtronic

INDUSTRY

Sponsor Role: collaborator

Canadian Critical Care Trials Group

OTHER

Sponsor Role: collaborator

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Karen J Bosma

Role: PRINCIPAL_INVESTIGATOR

London Health Sciences Centre, London, Ontario, Canada

Laurent Brochard

Role: PRINCIPAL_INVESTIGATOR

St. Michael's Hospital, Toronto, Ontario, Canada

Locations

El Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"

Buenos Aires, , Argentina

Kingston General Hospital

Kingston, Ontario, Canada

London Health Sciences Centre - University Hospital

London, Ontario, Canada

Victoria Hospital

London, Ontario, Canada

Sunnybrook Hospital - Health Sciences Centre

Toronto, Ontario, Canada

North York General Hospital

Toronto, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

UHN- Toronto General Hospital

Toronto, Ontario, Canada

UHN- Toronto Western Hospital

Toronto, Ontario, Canada

Centre hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, Canada

Royal Victoria Hospital

Montreal, Quebec, Canada

Institut Universitaire de cardiologie et de pneumologie de Quebec

Québec, Quebec, Canada

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, , France

University Hospital of Heraklion

Heraklion, , Greece

University Hospital of Ferrara

Ferrara, , Italy

San Giovanni Battista University Hospital

Turin, , Italy

King Abdulaziz Medical City

Riyadh, , Saudi Arabia

Hospital de Sant Pau

Barcelona, , Spain

Countries

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

References

Bosma KJ, Burns KEA, Martin CM, Skrobik Y, Mancebo Cortes J, Mulligan S, Lafreniere-Roula M, Thorpe KE, Suarez Montero JC, Moran Chorro I, Rodriguez-Farre N, Butler R, Bentall T, Beduneau G, Enguerrand P, Santos M, Piraino T, Spadaro S, Montanaro F, Basmaji J, Campbell E, Mercat A, Beloncle FM, Carteaux G, Maraffi T, Charbonney E, Lecronier M, Dres M, Arabi YM, Amaral ACK, Marinoff N, Adhikari NKJ, Geagea A, Shin P, Vaporidi K, Kondili E, Shahin J, Campisi J, Rodriguez PO, Setten M, Goligher EC, Ferguson ND, Fanelli V, Ferreyra G, Lellouche F, Sibley S, Brochard L; PROMIZING Study Investigators, the Canadian Critical Care Trials Group, and the REVA Network. Proportional-Assist Ventilation for Minimizing the Duration of Mechanical Ventilation. N Engl J Med. 2025 Sep 18;393(11):1088-1103. doi: 10.1056/NEJMoa2505708. Epub 2025 Jun 13.

Reference Type: DERIVED

PMID: 40513024 (View on PubMed)

Bosma KJ, Lafreniere-Roula M, Jiang A, Heath A, Ouyang Y, Wade K, Hu P, Burns KEA, Martin CM, Skrobik Y, Mulligan S, Thorpe KE, Brochard L; members of the Canadian Critical Care Trials Group and the REVA Network. Proportional Assist Ventilation for Minimizing the Duration of Mechanical Ventilation (the PROMIZING study): update to the statistical analysis plan for a randomized controlled trial. Trials. 2024 Dec 30;25(1):855. doi: 10.1186/s13063-024-08669-7.

Reference Type: DERIVED

PMID: 39736673 (View on PubMed)

Bosma KJ, Martin CM, Burns KEA, Mancebo Cortes J, Suarez Montero JC, Skrobik Y, Thorpe KE, Amaral ACK, Arabi Y, Basmaji J, Beduneau G, Beloncle F, Carteaux G, Charbonney E, Demoule A, Dres M, Fanelli V, Geagea A, Goligher E, Lellouche F, Maraffi T, Mercat A, Rodriguez PO, Shahin J, Sibley S, Spadaro S, Vaporidi K, Wilcox ME, Brochard L; Canadian Critical Care Trials Group and; REVA Network. Study protocol for a randomized controlled trial of Proportional Assist Ventilation for Minimizing the Duration of Mechanical Ventilation: the PROMIZING study. Trials. 2023 Mar 27;24(1):232. doi: 10.1186/s13063-023-07163-w.

Reference Type: DERIVED

PMID: 36973743 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan: Original

View Document

Document Type: Statistical Analysis Plan: Updated

View Document

Related Links

https://promizingstudy.com/wp-content/uploads/2023/03/Trials-Promizing.pdf

Published Protocol

https://ccforum.biomedcentral.com/articles/10.1186/s13054-022-04063-4

The PROMIZING trial enrollment algorithm for early identification of patients ready for unassisted breathing

https://promizingstudy.com/

PROMIZING Website

Other Identifiers

IPR-327433, ISR-2014-10481

Identifier Type: -

Identifier Source: org_study_id