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

May 6, 2026 updated by: Ahmad Shaddad, Assiut University

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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
400

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Egypt
    • Assuit Egypt
      • Asyut, Assuit Egypt, Egypt, 71515
        • Recruiting
        • Assuit Univeristy
        • Contact:
        • Contact:
          • Ahmad Shaddad

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Successful Ventilatory Liberation Within 72 Hours
Time Frame: 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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Ventilatory Failure Within 7 Days
Time Frame: 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
Time Frame: 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
Time Frame: 90 days
All-cause mortality occurring within 90 days following ventilatory assessment. Unit of Measure: Percentage of participants.
90 days
Sustained Ventilatory Independence at 90 Days
Time Frame: 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
Time Frame: 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
Time Frame: 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

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Predictive Performance of the Clinical Load Index (CLI) for Ventilatory Liberation Within 72 Hours
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 72 hours
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)
Time Frame: 72 hours
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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 72 hours
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
Time Frame: 90 days
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
Time Frame: 90 days
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)
Time Frame: 72 hours
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
Time Frame: 72 hours
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
Time Frame: 72 hours
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
Time Frame: 72 hours
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
Time Frame: 72 hours
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
Time Frame: 72 hours
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
Time Frame: 72 hours
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
Time Frame: 90 days
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
Time Frame: 90 days
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
Time Frame: 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
Time Frame: 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
Time Frame: Baseline through 90-day follow-up
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
Time Frame: 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
Time Frame: 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
Time Frame: 90 days
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
Time Frame: 90 days
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
Time Frame: 90 days
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
Time Frame: 90 days
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
Time Frame: 90 days
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
Time Frame: 90 days
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
Time Frame: 90 days
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Assiut University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 29, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 1, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 6, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 11, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 11, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 6, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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