Real-Time Algorithm-Driven Ventilation Feedback to Improve Lung-Protective Ventilation in Critically Ill Patients (REALVENT)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Critical Illness; Respiratory Failure; ARDS (Acute Respiratory Distress Syndrome); VILI (Ventilator-induced Lung Injury)
• Intervention / Treatment: Device: REal-time Algorithm-driven Ventilation feedback to improve lung-protective ventilation in critically; Other: Standard ICU care

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 208
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Longxiang Su, Doctor; Phone Number: +86 15652797257; Email: slx77@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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
• Chronic ventilator dependence, defined as ≥ 21 consecutive days of mechanical ventilation prior to the current admission
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: REal-time Algorithm-driven Ventilation feedback to improve lung-protective ventilation in critically; Patients in the intervention arm will receive real-time ventilator waveform monitoring through the respiratory dynamics monitoring and feedback RemoteVentilate ViewTM system. The system continuously collects high-frequency waveform data (flow, pressure, volume) directly from the ventilator interface and analyses the following metrics: Tidal volume (VT) indexed to predicted body weight, Driving pressure (ΔP), Plateau pressure (Pplat), and Mechanical power (MP). Patient-ventilator asynchrony (PVA) events will be also collected in the system, including double triggering, ineffective efforts, reverse triggering, and flow starvation, ect	Device: REal-time Algorithm-driven Ventilation feedback to improve lung-protective ventilation in critically; Patients in the intervention arm will receive real-time ventilator waveform monitoring through the respiratory dynamics monitoring and feedback RemoteVentilate ViewTM system. The system continuously collects high-frequency waveform data (flow, pressure, volume) directly from the ventilator interface and analyses the following metrics: Tidal volume (VT) indexed to predicted body weight, Driving pressure (ΔP), Plateau pressure (Pplat), and Mechanical power (MP). Patient-ventilator asynchrony (PVA) events will be also collected in the system, including double triggering, ineffective efforts, reverse triggering, and flow starvation, ect..
Active Comparator: Standard ICU care; The control group will receive standard ICU care, including routine monitoring of ventilator parameters such as tidal volume, plateau pressure, and oxygenation status. No structured feedback or external ventilation reports will be provided. This reflects the prevailing standard of care in Chinese ICUs and is thus an appropriate comparator for assessing the added value of a real-time respiratory feedback platform.	Other: Standard ICU care; The control group will receive standard ICU care, including routine monitoring of ventilator parameters such as tidal volume, plateau pressure, and oxygenation status. No structured feedback or external ventilation reports will be provided. This reflects the prevailing standard of care in Chinese ICUs and is thus an appropriate comparator for assessing the added value of a real-time respiratory feedback platform.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The daily lung-protective ventilation achievement rate	The primary outcome is the daily lung-protective ventilation achievement rate over the first 72 hours following randomisation. Lung-protective ventilation is defined as simultaneous fulfilment of all of the following four criteria: Tidal volume (VT) < 8 mL/kg predicted body weight (PBW); Driving pressure (ΔP) < 15 cmH₂O; Plateau pressure (Pplat) < 30 cmH₂O; Mechanical power (MP) < 17 J/min. The daily achievement rate is calculated as the number of hours within each 24-hour period where all four targets are met, divided by 24, and expressed as a percentage. The mean of the three daily rates over the 72-hour period will be used as the primary outcome. This outcome reflects both physiological safety and clinician behaviour, and was selected based on its strong mechanistic link with ventilator-induced lung injury and previous observational data on variability in adherence	Over the first 72 hours following randomisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilator-free days at day 28 (VFD-28)	defined as the number of days alive and free from invasive mechanical ventilation between randomisation and day 28, with patients who die before day 28 considered as having 0 VFDs;	Day 28 after trial enrollment
ICU length of stay	total number of days from ICU admission to ICU discharge;	28 days after ICU admission
Serum concentration of interleukin-1 beta (IL-1β)	Serum IL-1β concentration measured using standardized immunoassays.	Baseline (within 24hours) and 72 hours after trial enrollment
Serum concentration of interleukin-6 (IL-6)	Serum IL-6 concentration measured using standardized immunoassays.	Baseline (within 24hours) and 72 hours after trial enrollment
Serum concentration of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1)	Serum sTREM-1 concentration measured using standardized immunoassays.	Baseline (within 24hours) and 72 hours after trial enrollment
Incidence of ventilator-associated pneumonia (VAP)	based on CDC criteria, adjudicated by two independent reviewers;	72 hours after trial enrollment
Incidence of barotrauma	including pneumothorax, pneumomediastinum, or subcutaneous emphysema confirmed radiographically	72 hours after trial enrollment
ECMO initiation rate	proportion of patients who require extracorporeal support during the index ICU stay;	72 hours after trial enrollment
Mortality at day 28	all-cause mortality;	Day 28 after trial enrollment
Modified NASA Task Load Index (NASA-TLX) score (0-100)	Six-domain modified NASA-TLX; each domain rated 0-20; performance reverse-scored; mean transformed to 0-100; higher scores indicate greater perceived workload.	72 hours after trial enrollment
Clinician-reported usability score (mean of 5-item, 5-point Likert scale; range 1-5)	Five items rated 1-5; mean score reported; higher scores indicate better perceived usability.	72 hours after trial enrollment

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: Shandong Provincial Hospital; Henan Provincial People's Hospital; Chongqing General Hospital; Jinzhou Medical University; Beijing Hepingli Hospital; Beijing No.6 Hospital; Binzhou Second People's Hospital; Qujing Central Hospital of Yunnan Province; Capital Medical University Affiliated Beijing Anzhen Hospital, Nanchong Center

Publications and helpful links

General Publications

• Liu S, Zhao Z, Chen X, Chi Y, Yuan S, Cai F, Song Z, Ma Y, He H, Su L, Long Y. Evaluation of health care providers' ability to identify patient-ventilator triggering asynchrony in intensive care unit: a translational observational study in China. BMC Med Educ. 2025 Feb 4;25(1):182. doi: 10.1186/s12909-025-06638-5.
• Chen X, Yuan S, Kassis EB, Zhang S, Chi Y, Liu S, Cai F, Ma Y, Li Y, Su L, Long Y. Methodological development of the remote ventilate view platform for real-time monitoring of patient-ventilator asynchrony and respiratory parameters in severe pneumonia patients. J Intensive Med. 2025 Sep 23;5(4):367-376. doi: 10.1016/j.jointm.2025.07.003. eCollection 2025 Oct.
• Chen X, Fan J, Zhao W, Shi R, Guo N, Chang Z, Song M, Wang X, Chen Y, Li T, Li GG, Su L, Long Y; on bahalf of Beijing Dongcheng Critical Care Quality Control Centre Group. Application of a cloud platform that identifies patient-ventilator asynchrony and enables continuous monitoring of mechanical ventilation in intensive care unit. Heliyon. 2024 Jun 27;10(13):e33692. doi: 10.1016/j.heliyon.2024.e33692. eCollection 2024 Jul 15.
• Su L, Lan Y, Chi Y, Cai F, Bai Z, Liu X, Huang X, Zhang S, Long Y. Establishment and Application of a Patient-Ventilator Asynchrony Remote Network Platform for ICU Mechanical Ventilation: A Retrospective Study. J Clin Med. 2023 Feb 16;12(4):1570. doi: 10.3390/jcm12041570.

Study record dates

Study Major Dates

• Study Start (Estimated): December 30, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): July 30, 2026

Study Registration Dates

• First Submitted: December 2, 2025
• First Submitted That Met QC Criteria: December 14, 2025
• First Posted (Actual): December 29, 2025

Study Record Updates

• Last Update Posted (Actual): December 29, 2025
• Last Update Submitted That Met QC Criteria: December 14, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Lung Injury; Pathological Conditions, Signs and Symptoms; Respiratory Insufficiency; Critical Illness; Ventilator-Induced Lung Injury; Acute Lung Injury
• Other Study ID Numbers: K6526

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Time Frame: 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.
• IPD Sharing Access Criteria: 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No