Phenotype-Guided Weaning in Mechanically Ventilated Patients With Chronic Comorbidities

NCT07594418 | Not Yet Recruiting DMC

• 1 other identifier: Phenotype-Weaning-Chronic
• Study Type: interventional
• Target: 1,380
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Chronic Disease; Mechanical Ventilation Weaning

Keywords

Phenotype-Guided Weaning; Ventilator Liberation; Ventilator-Free Days; Chronic Comorbidities; Spontaneous Breathing Trial; ABCDE Screening

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Number of Participants With Intensive Care Unit or Hospital Mortality

  Day 28 and day 90 after enrollment

• Time From Enrollment to Successful Weaning

  From enrollment to day 28

• Number of Participants in Each Weaning Outcome Category

  From enrollment to day 28

Study Arms (2)

Phenotype-Guided Weaning Strategy

EXPERIMENTAL

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

Standard Care

ACTIVE COMPARATOR

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

Interventions

Phenotype-Guided Weaning Strategy OTHER

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.

Phenotype-Guided Weaning Strategy

Standard Care OTHER

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.

Standard Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older.
• 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.
• Receiving invasive mechanical ventilation for at least 24 hours and expected to require mechanical ventilation for at least 72 hours.
• Not receiving neuromuscular blocking agents and having a Richmond Agitation-Sedation Scale score of -3 or higher.
• PaO2/FiO2 of 150 mmHg or higher.

You may not qualify if:

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

Sponsors & Collaborators

• Southeast University, China: lead

MeSH Terms

Conditions

Chronic Disease

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Ling Liu, phD

  Zhongda Hospital, School of Medicine, Southeast University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yang Li, MD

CONTACT

+8615651782917; liyangseu@yeah.net

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Critical Care Medicine; Principal Investigator

Model Details: This is a stepped-wedge cluster randomized trial. Intensive care units are randomized as clusters. All clusters start in the standard care period and then sequentially cross over to the phenotype-guided weaning intervention according to a pre-specified randomized sequence. Individual participants do not cross over between study conditions.

Study Record Dates

• First Submitted: May 12, 2026
• First Posted: May 18, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: May 19, 2026

Record last verified: 2026-05