CLEAR Model for Predicting Ventilatory Liberation in Severe COPD

NCT07579052 | Recruiting

• 2 other identifiers: 2026-12-510.17605/OSF.IO/A42U5
• Study Type: observational
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective observational cohort study aims to prospectively evaluate and validate the Clinical Load, Exchange, Ability of Respiration, and Reserve (CLEAR) model for predicting sustained ventilatory liberation in patients with severe chronic obstructive pulmonary disease (COPD) receiving invasive mechanical ventilation (MV) or non-invasive ventilation (NIV). Two parallel cohorts will be studied: CLEAR-MV for patients undergoing spontaneous breathing trials (SBT) and CLEAR-NIV for patients undergoing NIV withdrawal trials. The model integrates diaphragm ultrasound evaluating diaphragm thickening fraction (DTF), ventilatory load indices including the rapid shallow breathing index (RSBI) or Clinical Load Index (CLI), gas exchange parameters including Potential of Hydrogen (pH), partial pressure of carbon dioxide (PaCO₂), and its change over time (ΔPaCO₂) combined as the Gas Exchange Index (GEI), and peripheral muscle reserve assessing rectus femoris (RF) and vastus intermedius (VI) thickness. The primary outcome is successful liberation from ventilatory support within 72 hours. Secondary outcomes include ventilatory failure within 7 days, ventilator- or NIV-free days at 28 days, and time-fixed 90-day clinical outcomes including all-cause mortality, sustained ventilatory independence, and rehospitalization for respiratory failure. Model performance will be evaluated using discrimination (area under the receiver operating characteristic curve), calibration (calibration intercept and slope), and clinical utility (decision curve analysis and net benefit) and compared with prespecified established ventilatory indices, including the Rapid Shallow Breathing Index (RSBI) and Integrative Weaning Index (IWI) in the invasive mechanical ventilation cohort, and the Heart rate, Acidosis, Consciousness, Oxygenation, and Respiratory rate (HACOR) score and the ratio of peripheral oxygen saturation to fraction of inspired oxygen divided by respiratory rate (ROX) index in the non-invasive ventilation cohort.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

COPD; Mechanical Ventilation; Non-Invasive Ventilation; Weaning; Ventilator Liberation; Diaphragm Ultrasound; Respiratory Muscle; Predictive Model; Intensive Care Unit

Outcome Measures

Primary Outcomes (1)

• Successful Ventilatory Liberation Within 72 Hours

  Successful liberation from ventilatory support defined as absence of ventilatory failure within 72 hours. In CLEAR-MV, this is defined as no reintubation within 72 hours following extubation. In CLEAR-NIV, this is defined as no restart of non-invasive ventilation or escalation to invasive mechanical ventilation within 72 hours following withdrawal. The Clinical Load, Exchange, Ability, and Reserve (CLEAR) model is a novel multidomain ventilatory assessment framework undergoing prospective derivation and validation in this study to estimate the probability of successful ventilatory liberation and related clinical outcomes. Specific bedside thresholds and operational score ranges have not yet been established. Higher CLEAR model performance values are anticipated to correlate with improved prediction of successful ventilatory liberation and favorable clinical outcomes. Unit of Measure: Percentage of participants.

  72 hours

Secondary Outcomes (6)

• Ventilatory Failure Within 7 Days

  7 days

• Ventilator-Free Days at 28 Days

  28 days

• 90-Day All-Cause Mortality

  90 days

• Sustained Ventilatory Independence at 90 Days

  90 days

• Rehospitalization for Respiratory Failure at 90 Days

  90 days

Other Outcomes (33)

• Predictive Performance of the Clinical Load Index (CLI) for Ventilatory Liberation Within 72 Hours

  72 hours

• Predictive Performance of the Gas Exchange Index (GEI) for Ventilatory Liberation Within 72 Hours

  72 hours

• Incremental Discrimination Performance of the Clinical Load Index (CLI) for Ventilatory Liberation Within 72 Hours

  72 hours

Study Arms (2)

CLEAR-MV

Adults with severe chronic obstructive pulmonary disease (COPD) receiving invasive mechanical ventilation and undergoing spontaneous breathing trial (SBT) assessment for ventilatory liberation. Patients are evaluated using the CLEAR domains (Load, Exchange, Ability, and Reserve) at the time of SBT.

CLEAR-NIV

Adults with severe chronic obstructive pulmonary disease (COPD) receiving non-invasive ventilation (NIV) and undergoing structured withdrawal or low-support trial assessment for ventilatory liberation. Patients are evaluated using the CLEAR domains (Load, Exchange, Ability, and Reserve) at the time of NIV withdrawal.

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients aged ≥40 years with confirmed or clinically diagnosed chronic obstructive pulmonary disease (COPD) admitted to the intensive care unit with acute respiratory failure requiring ventilatory support will be enrolled. Patients will be classified into two prospective cohorts according to the mode of ventilatory support received as part of routine clinical care: an invasive mechanical ventilation cohort (CLEAR-MV) and a non-invasive ventilation cohort (CLEAR-NIV). Enrollment will occur at the time patients are considered clinically ready for ventilatory withdrawal assessment, either during a spontaneous breathing trial in the MV cohort or during a structured NIV withdrawal or low-support trial in the NIV cohort.

You may qualify if:

• Age ≥40 years
• Confirmed or clinically diagnosed chronic obstructive pulmonary disease (COPD) based on prior spirometry or consistent clinical history
• Admission to the intensive care unit (ICU) with acute respiratory failure requiring ventilatory support
• Receiving either:
• Invasive mechanical ventilation (MV), or Non-invasive ventilation (NIV)
• Considered clinically ready for ventilatory withdrawal: Undergoing spontaneous breathing trial (SBT) in the MV cohort Undergoing structured withdrawal or low-support trial in the NIV cohort

You may not qualify if:

• Age \<40 years
• Primary diagnosis other than COPD driving respiratory failure (e.g., isolated pneumonia, cardiogenic pulmonary edema without COPD exacerbation)
• Known neuromuscular disease affecting respiratory muscle function
• Significant chest wall deformity or restrictive thoracic disorder affecting ventilatory mechanics
• Presence of tracheostomy at baseline
• Hemodynamic instability requiring high-dose vasopressors at the time of assessment
• Inability to perform a diaphragm or muscle ultrasound (e.g., poor acoustic window, extensive dressings)
• Reduced level of consciousness precluding valid clinical assessment (outside expected NIV cohort context)
• Refusal of consent by patient or legal representative

Sponsors & Collaborators

• Assiut University: lead

Study Sites (1)

Assuit Univeristy

Asyut, Assuit Egypt, 71515, Egypt

RECRUITING

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ahmad M. Shaddad, MD

  Assiut University

  PRINCIPAL INVESTIGATOR

• Aliae A. Hussien, MD

  Assiut University

  PRINCIPAL INVESTIGATOR

• Maiada K. Hashem, MD

  Assiut University

  PRINCIPAL INVESTIGATOR

• Abdekrahman M. Korany, MBBS

  Assiut University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ahmad M. Shaddad, MD

CONTACT

+201111171930; shaddad_ahmad@aun.edu.eg

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 1, 2026
• First Posted: May 11, 2026
• Study Start: April 29, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: May 11, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Data will be available beginning 6 months after publication and for up to 3 years thereafter.
• Access Criteria: Access will be granted to qualified researchers who submit a methodologically sound research proposal and statistical analysis plan. Requests will be reviewed by the principal investigator and approved by the Faculty of Medicine Research Ethics Committee, Assiut University. Data will be provided in de-identified form only, and access will require a signed data use agreement specifying permitted uses, data security measures, and prohibition of re-identification. Data sharing will comply with the research governance and data protection regulations of Assiut University.

Locations

EG (1)