The REALVENT trial is designed to evaluate whether a real-time, algorithm-driven ventilation feedback strategy can improve lung-protective ventilation (LPV) achievement rates in critically ill patients receiving invasive mechanical ventilation. This multicentre randomised controlled trial will compare real-time respiratory waveform monitoring with automated feedback against standard ICU care. The primary endpoint is the LPV achievement rate over the first 72 hours.

Mechanical ventilation is essential in modern intensive care but may cause ventilator-induced lung injury (VILI) when delivered with excessive tidal volume, airway pressure, or mechanical power, or in the presence of unrecognised patient-ventilator asynchrony. Despite guideline recommendations to limit tidal volume, plateau pressure, and driving pressure, real-world adherence to lung-protective ventilation (LPV) remains suboptimal, and clinicians often rely on intermittent, manual review of ventilator settings and waveforms.

The REALVENT trial tests a cloud-based respiratory dynamics monitoring and feedback system that continuously acquires high-frequency ventilator waveforms (pressure, flow, volume) and automatically computes key LPV metrics, including tidal volume indexed to predicted body weight, driving pressure, plateau pressure, mechanical power, and patient-ventilator asynchrony events. For patients in the intervention arm, the platform provides three layers of feedback over the first 72 hours after randomisation: (1) real-time alerts when LPV thresholds are exceeded; (2) 4-hour window indicator checks to capture sustained deviations; and (3) standardised 24-hour summary reports with recommendations for ventilator adjustment. These reports are reviewed by bedside clinicians and a central monitoring team, but all treatment decisions remain at the discretion of the local ICU team.

The control group receives usual care with standard bedside ventilator monitoring but without structured feedback from the platform. All other aspects of care, including fluid management, sedation, prone positioning, neuromuscular blockade, and adjunct respiratory monitoring (e.g., esophageal manometry or EIT), are left to clinician judgement and recorded.

The primary hypothesis is that algorithm-driven feedback will increase the proportion of time during the first 72 hours that all four LPV targets are simultaneously achieved compared with standard care. Secondary hypotheses are that improved LPV adherence will translate into more ventilator-free days, fewer ventilator-associated complications, lower inflammatory biomarker levels, and acceptable clinician workload and usability ratings.

Inclusion Criteria:

• Age between 18 and 75 years
• Receiving invasive mechanical ventilation via endotracheal intubation at the time of screening
• Initiation of invasive mechanical ventilation within the past 24 hours
• PaO₂/FiO₂ ≤ 200 mmHg on PEEP ≥ 8 cmH₂O or, if arterial blood gas is unavailable: SpO₂/FiO₂ ≤ 235 with SpO₂ ≤ 97%
• Chest imaging (chest X-ray or CT) showing bilateral pulmonary infiltrates not fully explained by pleural effusions, lobar collapse, or pulmonary nodules
• Respiratory failure not fully explained by cardiac failure or fluid overload
• Expected to require invasive mechanical ventilation for ≥ 72 hours after enrollment

Exclusion Criteria:

• Receipt of extracorporeal membrane oxygenation (ECMO) or high-frequency oscillatory ventilation at screening
• Brain death or anticipated withdrawal of life-sustaining treatment within 72 hours
• Pregnancy
• Known neuromuscular disease affecting spontaneous respiratory effort
• Prisoners or individuals unable to provide informed consent or surrogate consent
• Simultaneous enrollment in another interventional ICU study
• Lack of digital infrastructure for real-time ventilator waveform acquisition

De-identified individual participant data underlying the primary and secondary outcome results (including the final trial dataset and data dictionary) may be shared with qualified investigators for methodologically sound proposals, after publication of the main results and subject to institutional and ethical approvals. Data will be shared via secure data transfer agreements and will not contain any directly identifiable information.

Data will become available within one year of completion of the final follow up assessment, or within one year of primary manuscript publication, whichever comes first. Data will be available for 10 years.

Outside investigators who wish to use data will submit a formal request, including rationale, analysis plan, and local Institutional Review Board (IRB) determination. Sponsor will review and respond to all requests. All data sharing will be codified by the appropriate contract / data use agreement. Recipient researchers must promise in writing to never attempt to access identifiable health/medical information or to attempt to identify the subject(s) who provided the specimen/data. Any intent to use materials or data for commercial purposes must be clearly disclosed as part of the request.

Due to the nature of the intervention, treating clinicians and bedside staff will not be blinded to group allocation. The real-time feedback reports and alerts generated by the respiratory dynamics monitoring and feedback RVV systemTM are inherently visible to the ICU team and require bedside review and interpretation, precluding clinician blinding. However, the following personnel will remain blinded to group allocation throughout the study: ①Outcome assessors (data analysts reviewing ventilator-free days, inflammatory biomarkers detection, VAP, barotrauma, mortality); ②The core biostatistical team responsible for primary and secondary outcome analyses; ③Members of the independent Data Monitoring Committee (DMC) reviewing interim safety data.