Trials · 29 authors, 28 centres
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This protocol describes the PROMIZING trial, a multi-centre RCT comparing proportional assist ventilation (PAV+) to pressure support ventilation (PSV) in difficult-to-wean patients with acute respiratory failure. The primary outcome is time to successful liberation from mechanical ventilation, with a target sample size of 558 patients. If PAV+ reduces ventilation duration, it could improve patient outcomes and reduce healthcare costs.
**Background:** Patients with acute respiratory failure (ARF) require invasive mechanical ventilation (MV) to support breathing until recovery. Prolonged MV is associated with increased morbidity, mortality, and healthcare costs. Proportional assist ventilation with load-adjustable gain factors (PAV+) delivers assistance proportional to patient effort and may improve patient-ventilator synchrony and physiological response compared to pressure support ventilation (PSV), the current standard of care. Small studies have shown short-term advantages of PAV+, but no large RCT has evaluated clinically important outcomes.
**Methods:** The PROMIZING study is a multi-centre, randomized, parallel assignment, open-label clinical trial with a superiority framework. Approximately 20 ICUs in Canada, France, Italy, Spain, Saudi Arabia, Greece, and Argentina will participate. Eligible patients are adults (≥18 years) on MV for ARF for ≥24 hours, tolerating PSV for at least 30 minutes but not yet ready for extubation. A staged recruitment process includes screening, enrolment, a 30-minute Pressure Support Tolerance Trial (PS 5–20 cmH2O above PEEP), weaning criteria assessment, a 2-minute Zero CPAP Trial (0 cmH2O, FiO2 0.40), and a spontaneous breathing trial (SBT) on t-piece. Patients who pass the SBT are excluded from randomization. To be randomized, patients must either fail to meet weaning criteria, fail the Zero CPAP Trial, or fail the SBT. Randomization is 1:1 to PAV+ or PSV, stratified by site with variable block sizes, using a centralized electronic system (Medidata Rave). The study is open-label; the statistician is blinded. PAV+ is set to target a muscular pressure of 5–10 cmH2O. The weaning process is identical in both arms, with daily assessments and SBTs on t-piece. The primary outcome is time from randomization to successful liberation from invasive MV, defined as extubation (or tracheostomy disconnection) with no reintubation for 7 days, or until ICU or hospital discharge. Death is treated as a competing risk. Secondary outcomes include ventilator-free days at days 14, 21, and 28; time to ICU and hospital discharge (up to day 90); ICU, hospital, and 14-, 21-, 28-, and 90-day mortality; weaning progress and complications; and safety endpoints. Sample size calculation, refined using blinded data from the first 120 patients, showed a median time to successful liberation of 6.8 days. Using a hazard ratio of 1.30 (alpha 0.05, power 80%), 529 patients are required; with 5% loss to follow-up, the minimum is 558 patients (279 per group). Recruitment began September 2016, was suspended in April 2020 due to COVID-19, and resumed on a site-by-site basis. Completion was anticipated in 2023.
**Key Results:** This is a protocol paper; no results are reported. The paper describes the rationale, design, and statistical analysis plan for an ongoing trial.
**Clinical Implications:** If PAV+ reduces time to successful liberation from MV compared to PSV, it could improve patient outcomes (reduced morbidity, discomfort, and long-term functional impairment) and decrease healthcare costs. The study targets the difficult-to-wean population most likely to benefit, uses a rigorous enrolment algorithm to ensure patients are not ready for extubation at randomization, and employs a conservative 7-day definition of successful liberation. The multi-national design enhances external validity.