Phenotype-Guided Weaning in Mechanically Ventilated Patients With Chronic Comorbidities

Effect of a Phenotype-Guided Precision Intervention Strategy on 28-Day Ventilator-Free Days in Mechanically Ventilated Patients With Chronic Comorbidities: A Multicenter Open-Label Randomized Controlled Trial

The goal of this clinical trial is to learn whether a phenotype-guided weaning strategy can help adults with chronic comorbidities be liberated from invasive mechanical ventilation earlier. It will also learn about the safety of this strategy.

The main questions it aims to answer are:

• Does the phenotype-guided weaning strategy increase the number of ventilator-free days within 28 days after enrollment?
• Does the strategy improve the process and success of ventilator liberation?
• What safety events occur when this strategy is used?

Researchers will compare the phenotype-guided weaning strategy with standard care in mechanically ventilated patients with chronic cardiovascular, cerebrovascular, or respiratory comorbidities.

In the intervention period, participants will receive a protocolized ventilator weaning pathway. This pathway includes assisted ventilation transition, daily weaning readiness screening, a 0 cmH2O continuous positive airway pressure test, spontaneous breathing trial, extubation assessment, and post-extubation respiratory support when appropriate.

The phenotype-guided part of the strategy is mainly used for participants who fail a spontaneous breathing trial or have difficult weaning. These participants will undergo structured ABCDE screening to identify the main phenotype or mechanism of weaning failure:

• A: airway or lung dysfunction
• B: brain dysfunction, including delirium, anxiety, agitation, or impaired consciousness
• C: cardiac dysfunction
• D: diaphragm or respiratory muscle dysfunction
• E: endocrine, metabolic, or nutritional problems

Based on the identified phenotype, clinicians will provide targeted assessment and treatment. Participants will be followed for ventilator-free days through day 28 and for clinical outcomes through day 90.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Disease; Mechanical Ventilation Weaning
• Intervention / Treatment: Other: Phenotype-Guided Weaning Strategy; Other: Standard Care

• Study Type: Interventional
• Enrollment (Estimated): 1380
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yang Li, MD; Phone Number: +8615651782917; Email: liyangseu@yeah.net

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 18 years or older.
2. Presence of at least one chronic cardiovascular, cerebrovascular, or respiratory comorbidity. Cardiovascular and cerebrovascular comorbidities include stroke, hypertension, ischemic heart disease, valvular heart disease, heart failure, pulmonary heart disease, cardiomyopathy, and arrhythmia. Respiratory comorbidities include chronic obstructive pulmonary disease, asthma, bronchitis, emphysema, interstitial lung disease, and pneumoconiosis. These conditions will be identified according to the International Classification of Diseases 11th Revision diagnosis codes.
3. Receiving invasive mechanical ventilation for at least 24 hours and expected to require mechanical ventilation for at least 72 hours.
4. Not receiving neuromuscular blocking agents and having a Richmond Agitation-Sedation Scale score of -3 or higher.
5. PaO2/FiO2 of 150 mmHg or higher.

Exclusion Criteria:

1. Severe neuromuscular disease, such as Guillain-Barre syndrome, myasthenia gravis, amyotrophic lateral sclerosis, multiple sclerosis, or high spinal cord injury.
2. Severe dysfunction of other organs with expected death in the short term.
3. Severe end-stage irreversible respiratory, cardiac, neurological, or malignant disease, or receiving palliative care.
4. Pregnancy.
5. Participation in another clinical study.
6. Written informed consent not provided.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phenotype-Guided Weaning Strategy; During the intervention period, participants receive standard intensive care plus a protocolized phenotype-guided weaning strategy. The strategy includes assisted ventilation transition, daily weaning readiness screening, a 0 cmH2O continuous positive airway pressure test, spontaneous breathing trial, extubation assessment, and post-extubation respiratory support when appropriate. For participants who fail a spontaneous breathing trial or have difficult weaning, structured ABCDE screening is used to identify the dominant phenotype of weaning failure, including airway or lung dysfunction, brain dysfunction, cardiac dysfunction, diaphragm or respiratory muscle dysfunction, and endocrine, metabolic, or nutritional problems. Targeted management is provided according to the identified phenotype.	Other: Phenotype-Guided Weaning Strategy; A protocolized phenotype-guided strategy for ventilator liberation. The pathway includes assisted ventilation transition, daily weaning readiness screening, a 0 cmH2O continuous positive airway pressure test, spontaneous breathing trial, extubation assessment, and post-extubation respiratory support when appropriate. The key phenotype-guided component is applied to participants with spontaneous breathing trial failure or difficult weaning. These participants undergo structured ABCDE screening to identify the dominant mechanism of weaning failure: A, airway or lung dysfunction; B, brain dysfunction; C, cardiac dysfunction; D, diaphragm or respiratory muscle dysfunction; and E, endocrine, metabolic, or nutritional problems. Targeted evaluation and treatment are then provided according to the identified phenotype.
Active Comparator: Standard Care; During the control period, participants receive usual mechanical ventilation and weaning management according to each center's routine clinical practice and current guidelines. Management may include ventilator mode and parameter adjustment, treatment of underlying disease and complications, analgesia and sedation, fluid and hemodynamic management, nutrition, early mobilization and rehabilitation, airway management, weaning readiness assessment, spontaneous breathing trial, extubation assessment, and post-extubation respiratory support as determined by the treating clinical team.	Other: Standard Care; Usual mechanical ventilation and weaning management according to each center's routine clinical practice and current guidelines. The treating clinical team determines ventilator settings, weaning readiness assessment, spontaneous breathing trial, extubation assessment, post-extubation respiratory support, and related supportive care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of 28-Day Ventilator-Free Days	Ventilator-free days are defined as the number of days within 28 days after enrollment during which the participant is alive and free from invasive mechanical ventilation for at least 24 consecutive hours. Participants who die before day 28 or who remain mechanically ventilated at day 28 will be assigned zero ventilator-free days.	From enrollment to day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Intensive Care Unit or Hospital Mortality	Intensive care unit mortality and hospital mortality will be assessed at day 28 and day 90 after enrollment.	Day 28 and day 90 after enrollment
Time From Enrollment to Successful Weaning	Time from enrollment to successful weaning. For intubated participants, successful weaning is defined as no death or reintubation within 7 days after extubation, or discharge from the intensive care unit within 7 days without invasive mechanical ventilation, whichever occurs first. For tracheostomized participants, successful weaning is defined as 7 consecutive days of spontaneous breathing through the tracheostomy without any mechanical ventilation, or discharge while breathing spontaneously, whichever occurs first.	From enrollment to day 28
Number of Participants in Each Weaning Outcome Category	Participants will be classified into weaning outcome categories, including successful weaning, no weaning attempt, short weaning, difficult weaning, prolonged weaning success, and prolonged weaning failure.	From enrollment to day 28

Collaborators and Investigators

• Sponsor: Southeast University, China
• Investigators: Principal Investigator: Ling Liu, PHD, Zhongda Hospital, School of Medicine, Southeast University

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: May 12, 2026
• First Submitted That Met QC Criteria: May 12, 2026
• First Posted (Actual): May 18, 2026

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 17, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Ventilator-Free Days; Spontaneous Breathing Trial; Ventilator Liberation; Phenotype-Guided Weaning; Chronic Comorbidities; ABCDE Screening
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Pathological Conditions, Signs and Symptoms; Chronic Disease; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: Phenotype-Weaning-Chronic

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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