Phenotype-Guided Weaning in Mechanically Ventilated Patients With Chronic Comorbidities

Official title

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

Overview

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.

Interventions

• 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
• 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.

Primary outcome measures

• Number of 28-Day Ventilator-Free Days [Time frame: From enrollment to day 28]

Secondary outcome measures (3)

• Number of Participants With Intensive Care Unit or Hospital Mortality [Time frame: Day 28 and day 90 after enrollment]
• Time From Enrollment to Successful Weaning [Time frame: From enrollment to day 28]
• Number of Participants in Each Weaning Outcome Category [Time frame: From enrollment to day 28]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07594418 · Phenotype-Weaning-Chronic

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗