CLEAR Model for Predicting Ventilatory Liberation in Severe COPD (CLEAR)

Prospective Development and Validation of the CLEAR Model for Predicting Ventilatory Liberation in Severe Chronic Obstructive Pulmonary Disease: A Cohort Study

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Obstructive Pulmonary Disease

Detailed Description

This study is a prospective, dual-cohort observational investigation designed to develop and internally validate the Clinical Load, Exchange, Ability of Respiration, and Reserve (CLEAR) model for predicting sustained liberation from ventilatory support in patients with severe chronic obstructive pulmonary disease (COPD). The study includes two parallel cohorts based on the mode of ventilatory support: an invasive mechanical ventilation (MV) cohort (CLEAR-MV) and a non-invasive ventilation (NIV) cohort (CLEAR-NIV). The model structure and domain composition are prespecified; parameter estimation involves applying a fixed framework rather than exploratory model development.

In this study, "development" refers exclusively to parameter estimation within a prespecified and structurally locked model framework. The model structure, domain composition, and variable definitions were defined prior to outcome analysis and are not subject to modification. No variable selection, structural changes, or data-driven model building procedures will be performed. Validation refers to performance assessment in an independent cohort using the same fixed model structure.

Eligible adult patients with COPD admitted to the intensive care unit (ICU) and receiving MV or NIV for acute respiratory failure will be enrolled. Patients will be assessed at the time of readiness for ventilatory withdrawal: during a spontaneous breathing trial (SBT) in the MV cohort and during a structured withdrawal or low-support trial in the NIV cohort.

The CLEAR framework comprises four domains: Clinical Load (L), Exchange (E), Ability of Respiration (A), and Reserve (R). The Ability domain integrates diaphragm contractility assessed by ultrasound-derived diaphragm thickening fraction (DTF) and functional endurance during SBT or NIV withdrawal trials. The Load domain is assessed using the rapid shallow breathing index (RSBI) in the MV cohort and a composite Clinical Load Index (CLI) in the NIV cohort, incorporating respiratory rate, work of breathing, dyspnea, and ventilatory support requirements. The Exchange domain is based on arterial blood gas parameters, including pH, partial pressure of carbon dioxide (PaCO₂), and the change in PaCO₂ (ΔPaCO₂), combined into a Gas Exchange Index (GEI) in the NIV cohort and used as a safety assessment in the MV cohort. The Reserve domain reflects systemic muscle capacity and is assessed using ultrasound-derived thicknesses of the Rectus Femoris (RF) and vastus intermedius (VI).

The primary outcome is successful liberation from ventilatory support within 72 hours, defined as the absence of reintubation in the MV cohort and the absence of NIV restart or escalation to invasive ventilation in the NIV cohort. Secondary outcomes include ventilatory failure within 7 days, ventilator- or NIV-free days at 28 days, and time-fixed 90-day outcomes including all-cause mortality, sustained ventilatory independence, and rehospitalization for respiratory failure.

Comparative analyses will be performed against prespecified established indices. In the MV cohort, CLEAR-MV will be compared with the Rapid Shallow Breathing Index (RSBI) and, where available, the Integrative Weaning Index (IWI), which combines static compliance, arterial oxygen saturation, and RSBI. In the NIV cohort, CLEAR-NIV will be compared with 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.

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).

Separate multivariable logistic regression models will be estimated within a derivation cohort and evaluated in a validation cohort according to the prespecified CLEAR framework. Model performance will be evaluated directly within the study cohorts, without resampling-based internal validation. The independent and incremental contribution of the Clinical Load Index (CLI) and Gas Exchange Index (GEI) will be specifically assessed. Additional prespecified analyses will include domain correlation, model ablation, and prespecified ventilatory support state-transition analysis if longitudinal support-state data are available. No distinction exists between model development and structure specification; all structural elements are fixed prior to analysis.

Model outputs will be translated into predefined bedside scoring representations consistent with the prespecified framework.

The CLEAR framework and its component indices (Clinical Load Index and Gas Exchange Index) were prospectively defined and structurally locked before outcome analysis in an open-access research data repository (Zenodo), Digital Object Identifiers (DOIs):

10.5281/zenodo.19929675, 10.5281/zenodo.19931693, 10.5281/zenodo.19932153).

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

• Study Contact: Name: Ahmad M. Shaddad, MD; Phone Number: +201111171930; Email: shaddad_ahmad@aun.edu.eg

Study Locations

• Egypt
  • Assuit Egypt
    • Asyut, Assuit Egypt, Egypt, 71515
      • Recruiting
      • Assuit Univeristy
      • Contact: Ahmad M. Shaddad, MD; Phone Number: +201111171930; Email: shaddad_ahmad@aun.edu.eg
      • Contact: Ahmad Shaddad

Participation Criteria

Eligibility Criteria

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

• 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.

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilatory Failure Within 7 Days	Failure of ventilatory liberation defined as reintubation in the invasive mechanical ventilation cohort or need for non-invasive ventilation restart or escalation to invasive ventilation within 7 days. Unit of Measure: Percentage of participants.	7 days
Ventilator-Free Days at 28 Days	Number of days alive and free from invasive ventilatory support within the first 28 days. Patients who die within 28 days are assigned zero free days. Unit of Measure: Days.	28 days
90-Day All-Cause Mortality	All-cause mortality occurring within 90 days following ventilatory assessment. Unit of Measure: Percentage of participants.	90 days
Sustained Ventilatory Independence at 90 Days	Proportion of patients remaining free from invasive or non-invasive ventilatory support within 90 days following initial liberation without need for reinitiation of ventilatory support. Unit of Measure: Percentage of participants.	90 days
Rehospitalization for Respiratory Failure at 90 Days	Hospital readmission due to respiratory failure requiring ventilatory support within 90 days. Unit of Measure: Percentage of participants.	90 days
Non-invasive Ventilation (NIV) Free Days at 28 Days	Number of days alive and free from non-invasive ventilatory support within the first 28 days. Patients who die within 28 days are assigned zero free days. Unit of Measure: Days.	28 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Predictive Performance of the Clinical Load Index (CLI) for Ventilatory Liberation Within 72 Hours	Evaluation of the discrimination performance of the Clinical Load Index (CLI) for prediction of successful ventilatory liberation within 72 hours using area under the receiver operating characteristic curve analysis. The Clinical Load Index (CLI) is a novel composite index undergoing initial derivation and validation in this study. Specific minimum and maximum score ranges and bedside threshold values have not yet been established. It is anticipated that higher calculated values will correlate with increased clinical load and reduced probability of successful ventilatory liberation. Unit of Measure: Area under the receiver operating characteristic curve (0-1 scale). Higher values indicate better discrimination performance.	72 hours
Predictive Performance of the Gas Exchange Index (GEI) for Ventilatory Liberation Within 72 Hours	Evaluation of the discrimination performance of the Gas Exchange Index (GEI), based on pH, partial pressure of carbon dioxide (PaCO₂), and change in PaCO₂ (ΔPaCO₂), for prediction of successful ventilatory liberation within 72 hours using area under the receiver operating characteristic curve analysis. The Gas Exchange Index (GEI) is a novel composite index undergoing initial derivation and validation in this study. Specific minimum and maximum score ranges and bedside threshold values have not yet been established. It is anticipated that higher calculated values will correlate with worsening gas exchange impairment and increased risk of ventilatory liberation failure. Unit of Measure: Area under the receiver operating characteristic curve (0-1 scale). Higher values indicate better discrimination performance.	72 hours
Incremental Discrimination Performance of the Clinical Load Index (CLI) for Ventilatory Liberation Within 72 Hours	Assessment of the incremental contribution of the Clinical Load Index (CLI) to the CLEAR model by evaluating changes in discrimination performance for prediction of successful ventilatory liberation within 72 hours compared with baseline models without CLI. The Clinical Load Index (CLI) is a novel composite index undergoing initial derivation and validation in this study. Specific minimum and maximum score ranges and bedside threshold values have not yet been established. It is anticipated that higher calculated values will correlate with increased clinical load and reduced probability of successful ventilatory liberation. Unit of Measure: Area under the receiver operating characteristic curve difference (0-1 scale). Higher values indicate greater incremental discrimination improvement.	72 hours
Association Between Clinical Load Index (CLI) Categories and Ventilatory Liberation Success	Assessment of the association between predefined Clinical Load Index (CLI) categories and successful ventilatory liberation within 72 hours. The Clinical Load Index (CLI) is a novel composite index undergoing initial derivation and validation in this study. Specific minimum and maximum score ranges and bedside threshold values have not yet been established. It is anticipated that higher calculated values will correlate with increased clinical load and reduced probability of successful ventilatory liberation. Unit of Measure: Percentage of participants.	72 hours
Discrimination Performance of CLEAR-MV Compared With Rapid Shallow Breathing Index (RSBI)	Assessment of discrimination performance using area under the receiver operating characteristic curve for prediction of ventilatory liberation within 72 hours. The Rapid Shallow Breathing Index (RSBI) is calculated as respiratory rate divided by tidal volume, typically ranging from 0 to approximately 200 breaths/min/L, with higher values indicating greater risk of ventilatory liberation failure. CLEAR-MV is a novel score undergoing derivation and validation in invasively ventilated patients to estimate probability of successful ventilatory liberation and related outcomes. Specific bedside thresholds and operational score ranges have not yet been established. Higher CLEAR-MV model performance values are anticipated to correlate with improved prediction of successful ventilatory liberation and favorable clinical outcomes. Unit of Measure: Area under the receiver operating characteristic curve (0-1 scale). Higher values indicate better discrimination performance.	72 hours
Correlation Analysis Between CLEAR Domains and Ventilatory Liberation Outcomes at 72 Hours	Assessment of correlations between CLEAR domain scores and ventilatory liberation outcomes at 72 hours using correlation coefficient analysis. The Clinical Load, Exchange, Ability, and Reserve (CLEAR) model is a novel multidomain ventilatory assessment framework undergoing prospective derivation and validation in this study. The model integrates physiological, respiratory, and functional domains to estimate the probability of successful ventilatory liberation and related clinical outcomes. Specific bedside thresholds and operational score ranges have not yet been established. It is anticipated that higher calculated CLEAR model performance values will correlate with improved prediction of successful ventilatory liberation and clinical outcomes. Unit of Measure: Correlation coefficients (-1 to +1 scale). Values farther from 0 indicate stronger correlation strength.	72 hours
Incremental Discrimination Performance of the Gas Exchange Index (GEI) for Ventilatory Liberation Within 72 Hours	Assessment of the incremental contribution of the Gas Exchange Index (GEI) to the CLEAR model by evaluating changes in discrimination performance for prediction of successful ventilatory liberation within 72 hours compared with baseline models without GEI. The Gas Exchange Index (GEI) is a novel composite index undergoing initial derivation and validation in this study. Specific minimum and maximum score ranges and bedside threshold values have not yet been established. It is anticipated that higher calculated values will correlate with worsening gas exchange impairment and increased risk of ventilatory liberation failure. Unit of Measure: Area under the receiver operating characteristic curve difference (0-1 scale). Higher values indicate greater incremental discrimination improvement.	72 hours
Incremental Calibration Performance of the Clinical Load Index (CLI) for Ventilatory Liberation Within 72 Hours	Assessment of the incremental contribution of the Clinical Load Index (CLI) to the CLEAR model by evaluating changes in calibration performance for prediction of successful ventilatory liberation within 72 hours compared with baseline models without CLI. Calibration performance will be assessed using calibration intercept and calibration slope. The Clinical Load Index (CLI) is a novel composite index undergoing initial derivation and validation in this study. Specific minimum and maximum score ranges and bedside threshold values have not yet been established. It is anticipated that higher calculated values will correlate with increased clinical load and reduced probability of successful ventilatory liberation. Unit of Measure: Unitless calibration coefficients. Calibration intercept values closer to 0 indicate better agreement between predicted and observed outcomes, while calibration slope values closer to 1 indicate optimal calibration performance.	72 hours
Incremental Calibration Performance of the Gas Exchange Index (GEI) for Ventilatory Liberation Within 72 Hours	Assessment of the incremental contribution of the Gas Exchange Index (GEI) to the CLEAR model by evaluating changes in calibration performance for prediction of successful ventilatory liberation within 72 hours compared with baseline models without GEI. Calibration performance will be assessed using calibration intercept and calibration slope. The Gas Exchange Index (GEI) is a novel composite index undergoing initial derivation and validation in this study. Specific minimum and maximum score ranges and bedside threshold values have not yet been established. It is anticipated that higher calculated values will correlate with worsening gas exchange impairment and increased risk of ventilatory liberation failure. Unit of Measure: Unitless calibration coefficients. Calibration intercept values closer to 0 indicate better agreement between predicted and observed outcomes, while calibration slope values closer to 1 indicate optimal calibration performance.	72 hours
Association Between Gas Exchange Index (GEI) Categories and Ventilatory Liberation Success	Assessment of the association between predefined Gas Exchange Index (GEI) categories and successful ventilatory liberation within 72 hours. The Gas Exchange Index (GEI) is a novel composite index undergoing initial derivation and validation in this study. Specific minimum and maximum score ranges and bedside threshold values have not yet been established. It is anticipated that higher calculated values will correlate with worsening gas exchange impairment and increased risk of ventilatory liberation failure. Unit of Measure: Percentage of participants.	72 hours
Association Between Clinical Load Index (CLI) Categories and 90-Day All-Cause Mortality	Assessment of the association between predefined Clinical Load Index (CLI) categories and 90-day all-cause mortality. The Clinical Load Index (CLI) is a novel composite index undergoing initial derivation and validation in this study. Specific minimum and maximum score ranges and bedside threshold values have not yet been established. It is anticipated that higher calculated values will correlate with increased clinical load and reduced probability of successful ventilatory liberation. Unit of Measure: Percentage of participants.	90 days
Association Between Gas Exchange Index (GEI) Categories and 90-Day All-Cause Mortality	Assessment of the association between predefined Gas Exchange Index (GEI) categories and 90-day all-cause mortality. The Gas Exchange Index (GEI) is a novel composite index undergoing initial derivation and validation in this study. Specific minimum and maximum score ranges and bedside threshold values have not yet been established. It is anticipated that higher calculated values will correlate with worsening gas exchange impairment and increased risk of ventilatory liberation failure. Unit of Measure: Percentage of participants.	90 days
Discrimination Performance of CLEAR-MV Compared With Integrative Weaning Index (IWI)	Assessment of discrimination performance using area under the receiver operating characteristic curve for prediction of ventilatory liberation within 72 hours. The Integrative Weaning Index (IWI) is a continuous scale typically ranging from near 0 to above 100, with higher values indicating greater probability of successful ventilatory liberation. CLEAR-MV is a novel multidomain ventilatory assessment framework undergoing prospective derivation and validation in invasively ventilated patients to estimate probability of successful ventilatory liberation and related clinical outcomes. Specific bedside thresholds and operational score ranges have not yet been established. Higher CLEAR-MV model performance values are anticipated to correlate with improved prediction of successful ventilatory liberation and favorable clinical outcomes. Unit of Measure: Area under the receiver operating characteristic curve (0-1 scale). Higher values indicate better discrimination performance.	72 hours
Discrimination Performance of CLEAR-NIV Compared With HACOR Score	Assessment of discrimination performance using area under the receiver operating characteristic curve for prediction of ventilatory liberation within 72 hours. The Heart rate, Acidosis, Consciousness, Oxygenation, and Respiratory rate (HACOR) score ranges from 0 to 25, with higher scores indicating greater risk of non-invasive ventilation failure. CLEAR-NIV is a novel multidomain ventilatory assessment framework undergoing derivation and validation in non-invasively ventilated patients to estimate probability of successful ventilatory liberation and related clinical outcomes. Specific bedside thresholds and operational score ranges have not yet been established. Higher CLEAR-NIV model performance values are anticipated to correlate with improved prediction of successful ventilatory liberation and favorable clinical outcomes. Unit of Measure: Area under the receiver operating characteristic curve (0-1 scale). Higher values indicate better discrimination performance.	72 hours
Discrimination Performance of CLEAR-NIV Compared With ROX Index	Assessment of discrimination performance using area under the receiver operating characteristic curve for prediction of ventilatory liberation within 72 hours. The ratio of oxygen saturation to fraction of inspired oxygen divided by respiratory rate (ROX) index typically ranges from approximately 2 to 20, with higher values indicating greater probability of successful non-invasive ventilatory support outcomes. CLEAR-NIV is a novel score undergoing derivation and validation in non-invasively ventilated patients to estimate probability of successful ventilatory liberation and related outcomes. Specific bedside thresholds and operational score ranges have not yet been established. Higher CLEAR-NIV performance values are anticipated to correlate with improved prediction of successful ventilatory liberation and favorable clinical outcomes. Unit of Measure: Area under the receiver operating characteristic curve (0-1 scale). Higher values indicate better discrimination performance.	72 hours
Calibration Performance of CLEAR-MV	Assessment of calibration performance using calibration intercept and calibration slope. The Clinical Load, Exchange, Ability, and Reserve for Mechanical Ventilation (CLEAR-MV) model is a novel multidomain ventilatory assessment framework undergoing prospective derivation and validation in this study for patients receiving invasive mechanical ventilation. The model integrates physiological, respiratory, and functional domains to estimate the probability of successful ventilatory liberation and related clinical outcomes. Specific bedside thresholds and operational score ranges have not yet been established. It is anticipated that higher calculated CLEAR-MV model performance values will correlate with improved prediction of successful ventilatory liberation and favorable clinical outcomes. Unit of Measure: Unitless calibration coefficients. Calibration intercept values closer to 0 and calibration slope values closer to 1 indicate better calibration performance.	72 hours
Calibration Performance of CLEAR-NIV	Assessment of calibration performance using calibration intercept and calibration slope. The Clinical Load, Exchange, Ability, and Reserve for Non-Invasive Ventilation (CLEAR-NIV) model is a novel multidomain ventilatory assessment framework undergoing prospective derivation and validation in this study for patients receiving non-invasive ventilatory support. The model integrates physiological, respiratory, and functional domains to estimate the probability of successful ventilatory liberation and related clinical outcomes. Specific bedside thresholds and operational score ranges have not yet been established. It is anticipated that higher calculated CLEAR-NIV model performance values will correlate with improved prediction of successful ventilatory liberation and favorable clinical outcomes. Unit of Measure: Unitless calibration coefficients. Calibration intercept values closer to 0 and calibration slope values closer to 1 indicate better calibration performance.	72 hours
Clinical Utility of CLEAR-MV	Assessment of clinical utility of the CLEAR-MV model using decision curve analysis and net benefit across clinically relevant threshold probabilities for prediction of successful ventilatory liberation. The Clinical Load, Exchange, Ability, and Reserve for Mechanical Ventilation (CLEAR-MV) model is a novel multidomain ventilatory assessment framework undergoing prospective derivation and validation in this study for patients receiving invasive mechanical ventilation. The model integrates physiological, respiratory, and functional domains to estimate the probability of successful ventilatory liberation and related clinical outcomes. Specific bedside thresholds and operational score ranges have not yet been established. It is anticipated that higher calculated CLEAR-MV model performance values will correlate with improved prediction of successful ventilatory liberation and favorable clinical outcomes. Unit of Measure: Net benefit (unitless).	72 hours
Clinical Utility of CLEAR-NIV	Assessment of clinical utility of the CLEAR-NIV model using decision curve analysis and net benefit across clinically relevant threshold probabilities for prediction of successful ventilatory liberation. The Clinical Load, Exchange, Ability, and Reserve for Non-Invasive Ventilation (CLEAR-NIV) model is a novel multidomain ventilatory assessment framework undergoing prospective derivation and validation in this study for patients receiving non-invasive ventilatory support. The model integrates physiological, respiratory, and functional domains to estimate the probability of successful ventilatory liberation and related clinical outcomes. Specific bedside thresholds and operational score ranges have not yet been established. It is anticipated that higher calculated CLEAR-NIV model performance values will correlate with improved prediction of successful ventilatory liberation and favorable clinical outcomes. Unit of Measure: Net benefit (unitless).	72 hours
Predictive Performance of the Clinical Load Index (CLI) for 90-Day All-Cause Mortality	Evaluation of the discrimination performance of the Clinical Load Index (CLI) for prediction of 90-day all-cause mortality using area under the receiver operating characteristic curve analysis. The Clinical Load Index (CLI) is a novel composite index undergoing initial derivation and validation in this study. Specific minimum and maximum score ranges and bedside threshold values have not yet been established. It is anticipated that higher calculated values will correlate with increased clinical load and reduced probability of successful ventilatory liberation. Unit of Measure: Area under the receiver operating characteristic curve (0-1 scale). Higher values indicate better discrimination performance.	90 days
Predictive Performance of the Gas Exchange Index (GEI) for 90-Day All-Cause Mortality	Evaluation of the discrimination performance of the Gas Exchange Index (GEI), based on pH, partial pressure of carbon dioxide (PaCO₂), and change in PaCO₂ (ΔPaCO₂), for prediction of 90-day all-cause mortality using area under the receiver operating characteristic curve analysis. The Gas Exchange Index (GEI) is a novel composite index undergoing initial derivation and validation in this study. Specific minimum and maximum score ranges and bedside threshold values have not yet been established. It is anticipated that higher calculated values will correlate with worsening gas exchange impairment and increased risk of ventilatory liberation failure. Unit of Measure: Area under the receiver operating characteristic curve (0-1 scale). Higher values indicate better discrimination performance.	90 days
Regression-Based Contribution Analysis of CLEAR Domains for Successful Ventilatory Liberation at 72 Hours	Assessment of the contribution of individual CLEAR domains to prediction of successful ventilatory liberation at 72 hours using regression coefficient analysis. The Clinical Load, Exchange, Ability, and Reserve (CLEAR) framework consists of two parallel ventilatory assessment models: CLEAR-MV for invasive mechanical ventilation and CLEAR-NIV for non-invasive ventilatory support. The models are novel multidomain frameworks undergoing prospective derivation and validation in this study and integrate physiological, respiratory, and functional domains to estimate the probability of successful ventilatory liberation and related clinical outcomes. Specific bedside thresholds and operational score ranges have not yet been established. It is anticipated that higher calculated CLEAR model performance values will correlate with improved prediction of successful ventilatory liberation and favorable clinical outcomes. Unit of Measure: Regression coefficients (unitless).	72 hours
Ablation Analysis of CLEAR Model Components for Successful Ventilatory Liberation at 72 Hours	Assessment of changes in predictive discrimination performance for successful ventilatory liberation at 72 hours following sequential removal of CLEAR model domains and components. The Clinical Load, Exchange, Ability, and Reserve (CLEAR) framework consists of two parallel multidomain ventilatory assessment models: CLEAR-MV for invasive mechanical ventilation and CLEAR-NIV for non-invasive ventilatory support undergoing derivation and validation to estimate 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: Area under the receiver operating characteristic curve difference (0-1 scale). Higher values indicate greater change in discrimination performance following model component removal.	72 hours
Ventilatory Support State-Transition Analysis	Assessment of transition patterns between invasive mechanical ventilation, non-invasive ventilation, ventilatory liberation, ventilatory support restart or escalation, discharge, and death using transition probability analysis and graphical state-flow methods. Unit of Measure: Transition probabilities.	Baseline through 90-day follow-up
Association Between Clinical Load Index (CLI) Categories and Sustained Ventilatory Independence at 90 Days	Assessment of the association between predefined Clinical Load Index (CLI) categories and sustained ventilatory independence within 90 days. The Clinical Load Index (CLI) is a novel composite index undergoing initial derivation and validation in this study. Specific minimum and maximum score ranges and bedside threshold values have not yet been established. It is anticipated that higher calculated values will correlate with increased clinical load and reduced probability of successful ventilatory liberation. Unit of Measure: Percentage of participants.	90 days
Association Between Gas Exchange Index (GEI) Categories and Sustained Ventilatory Independence at 90 Days	Assessment of the association between predefined Gas Exchange Index (GEI) categories and sustained ventilatory independence within 90 days. The Gas Exchange Index (GEI) is a novel composite index undergoing initial derivation and validation in this study. Specific minimum and maximum score ranges and bedside threshold values have not yet been established. It is anticipated that higher calculated values will correlate with worsening gas exchange impairment and increased risk of ventilatory liberation failure. Unit of Measure: Percentage of participants.	90 days
Incremental Discrimination Performance of the Clinical Load Index (CLI) for 90-Day All-Cause Mortality	Assessment of the incremental contribution of the Clinical Load Index (CLI) to the CLEAR model by evaluating changes in discrimination performance for prediction of 90-day all-cause mortality compared with baseline models without CLI. The Clinical Load Index (CLI) is a novel composite index undergoing initial derivation and validation in this study. Specific minimum and maximum score ranges and bedside threshold values have not yet been established. It is anticipated that higher calculated values will correlate with increased clinical load and reduced probability of successful ventilatory liberation. Unit of Measure: Area under the receiver operating characteristic curve difference (0-1 scale). Higher values indicate greater incremental discrimination improvement.	90 days
Incremental Discrimination Performance of the Gas Exchange Index (GEI) for 90-Day All-Cause Mortality	Assessment of the incremental contribution of the Gas Exchange Index (GEI) to the CLEAR model by evaluating changes in discrimination performance for prediction of 90-day all-cause mortality compared with baseline models without GEI. The Gas Exchange Index (GEI) is a novel composite index undergoing initial derivation and validation in this study. Specific minimum and maximum score ranges and bedside threshold values have not yet been established. It is anticipated that higher calculated values will correlate with worsening gas exchange impairment and increased risk of ventilatory liberation failure. Unit of Measure: Area under the receiver operating characteristic curve difference (0-1 scale). Higher values indicate greater incremental discrimination improvement.	90 days
Incremental Calibration Performance of the Clinical Load Index (CLI) for 90-Day All-Cause Mortality	Assessment of the incremental contribution of the Clinical Load Index (CLI) to the CLEAR model by evaluating changes in calibration performance for prediction of 90-day all-cause mortality compared with baseline models without CLI. Calibration performance will be assessed using calibration intercept and calibration slope. The Clinical Load Index (CLI) is a novel composite index undergoing initial derivation and validation in this study. Specific minimum and maximum score ranges and bedside threshold values have not yet been established. It is anticipated that higher calculated values will correlate with increased clinical load and reduced probability of successful ventilatory liberation. Unit of Measure: Unitless calibration coefficients. Calibration intercept values closer to 0 indicate better agreement between predicted and observed outcomes, while calibration slope values closer to 1 indicate optimal calibration performance.	90 days
Incremental Calibration Performance of the Gas Exchange Index (GEI) for 90-Day All-Cause Mortality	Assessment of the incremental contribution of the Gas Exchange Index (GEI) to the CLEAR model by evaluating changes in calibration performance for prediction of 90-day all-cause mortality compared with baseline models without GEI. Calibration performance will be assessed using calibration intercept and calibration slope. The Gas Exchange Index (GEI) is a novel composite index undergoing initial derivation and validation in this study. Specific minimum and maximum score ranges and bedside threshold values have not yet been established. It is anticipated that higher calculated values will correlate with worsening gas exchange impairment and increased risk of ventilatory liberation failure. Unit of Measure: Unitless calibration coefficients. Calibration intercept values closer to 0 indicate better agreement between predicted and observed outcomes, while calibration slope values closer to 1 indicate optimal calibration performance.	90 days
Correlation Analysis Between CLEAR Domains and 90-Day All-Cause Mortality	Assessment of correlations between CLEAR domain scores and 90-day all-cause mortality using correlation coefficient analysis. The Clinical Load, Exchange, Ability, and Reserve (CLEAR) framework consists of two parallel multidomain ventilatory assessment models: CLEAR-MV for invasive mechanical ventilation and CLEAR-NIV for non-invasive ventilatory support. The models are undergoing prospective derivation and validation to estimate 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: Correlation coefficients (-1 to +1 scale). Values farther from 0 indicate stronger correlation strength.	90 days
Regression-Based Contribution Analysis of CLEAR Domains for 90-Day All-Cause Mortality	Assessment of the contribution of individual CLEAR domains to prediction of 90-day all-cause mortality using regression coefficient analysis. The Clinical Load, Exchange, Ability, and Reserve (CLEAR) framework consists of two parallel ventilatory assessment models: CLEAR-MV for invasive mechanical ventilation and CLEAR-NIV for non-invasive ventilatory support. The models are novel multidomain frameworks undergoing prospective derivation and validation in this study and integrate physiological, respiratory, and functional domains to estimate the probability of successful ventilatory liberation and related clinical outcomes. Specific bedside thresholds and operational score ranges have not yet been established. It is anticipated that higher calculated CLEAR model performance values will correlate with improved prediction of successful ventilatory liberation and favorable clinical outcomes. Unit of Measure: Regression coefficients (unitless).	90 days
Ablation Analysis of CLEAR Model Components for 90-Day All-Cause Mortality	Assessment of changes in predictive discrimination performance for 90-day all-cause mortality following sequential removal of CLEAR model domains and components. The Clinical Load, Exchange, Ability, and Reserve (CLEAR) framework consists of two parallel multidomain ventilatory assessment models: CLEAR-MV for invasive mechanical ventilation and CLEAR-NIV for non-invasive ventilatory support. The models are undergoing prospective derivation and validation to estimate 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: Area under the receiver operating characteristic curve difference (0-1 scale). Higher values indicate greater change in discrimination performance following model component removal.	90 days

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Principal Investigator: Aliae A. Hussien, MD, Assiut University; Principal Investigator: Ahmad M. Shaddad, MD, Assiut University; Principal Investigator: Maiada K. Hashem, MD, Assiut University; Principal Investigator: Abdekrahman M. Korany, MBBS, Assiut University

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: May 1, 2026
• First Submitted That Met QC Criteria: May 6, 2026
• First Posted (Actual): May 11, 2026

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: COPD; Intensive Care Unit; Weaning; Mechanical Ventilation; Diaphragm Ultrasound; Non-Invasive Ventilation; Predictive Model; Respiratory Muscle; Ventilator Liberation
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pathological Conditions, Signs and Symptoms; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: 2026-12-5; 10.17605/OSF.IO/A42U5 (Registry Identifier: Open Science Framework (OSF))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) underlying the results reported in this study (including the data dictionary and statistical analysis code) will be made available upon reasonable request to qualified researchers. Data will be shared under a formal data use agreement after approval by the principal investigator and the institutional ethics committee of Assiut University. All shared datasets will be de-identified in accordance with applicable data protection standards, and no information that could directly identify participants will be released. Data sharing will comply with the research governance and data protection regulations of Assiut University and will be subject to approval by the Faculty of Medicine Research Ethics Committee.
• IPD Sharing Time Frame: Data will be available beginning 6 months after publication and for up to 3 years thereafter.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

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