Ultrasound of the Diaphragm Excursion Ratio as Physiological Biomarker in Acute Exacerbations of Chronic Obstructive Pulmonary Disease (Undated 2)

November 26, 2025 updated by: Wytze de Boer, Isala

3.1 Introduction and rationale In 2020 an estimate of 562.700 people had Chronic Obstructive Pulmonary Disease (COPD) in the Netherlands, resulting in 21.335 hospital admissions.[1] An acute exacerbation COPD (AECOPD) in combination with hospital admission is associated with high mortality and morbidity. [2]

Noninvasive ventilation (NIV) has been very effective in the context of AECOPD, since it efficiently offloads respiratory muscles and counteracts dynamic hyperinflation. This method often prevents intubation as a bridge to administering effective therapies (e.g., glucocorticoids, bronchodilators, and antibiotic agents)[3], and may reduce mortality.[4] Current guidelines recommend NIV for the treatment of acute respiratory failure in patients with respiratory distress, pH < 7.35, and PaCO2 > 6 kPA (with exclusion of patients requiring invasive ventilation, see guideline).[5,6] National guidelines do not recommend NIV in AECOPD with increased work of breathing without respiratory acidosis due to lack of evidence. [5]

Ultrasound of the diaphragm can identify atrophy and impaired motion or contractility of the diaphragm[10], and has been shown to predict mortality and NIV failure during NIV treatment for respiratory acidosis due to AECOPD.[11-15] Whether ultrasound of the diaphragm may predict mortality or need for (non-)invasive ventilation in AECOPD without respiratory acidosis on initial presentation is unknown.

During exploratory analysis of a previous study (unpublished; NCT05671198) we might have found a marker that has the potential to predict progression to NIV or death during hospitalization for AECOPD without respiratory acidosis:

The difference between diaphragm motion during tidal breathing and maximal breathing, used as a surrogate for inspiratory reserve volume (IRV), was significantly lower in patients requiring NIV or who died in-hospital compared to those who did not (1.59 cm, SD 1.91 vs. 3.14 cm, SD 2.45; p = 0.033). We performed a ROC curve analysis to assess the predictive value of these variables, which yielded an area under the ROC curve (AUROC) of 0.752 (95% CI: 0.535 - 0.968, p = 0.033), indicating a statistically significant discriminatory ability. The best cut-off value, as determined with the Youden's J statistic, was 1.74 cm, with a sensitivity of 86% and specificity of 70% for predicting NIV requirement or inhospital death.

However, the number of events was low and the study was primarily powered for another outcome. Therefore, prospective validation is needed before we impose treatment based on this marker. In case the suggested ultrasound measurement (see introduction) proofs to be a discriminatory marker for deterioration during hospitalization or predictive of progression to Non-Invasive Ventilation, we hope to be able to perform a follow-up study in which patient will be randomized to either standard of care or 'elective' NIV (to avoid emergency NIV need) based on yet to determine cut-off values.

3.2 Design (including population, method, confounders and outcomes) A multi-center, prospective observational cohort study conducted at Isala Hospital and UMCG aimed at determining the value of the sonographic motion ratio (tidal/maximum) of the diaphragm in AECOPD after hospital admission. After enrollment, the sonographic diaphragm motion will be assessed as additional measurement during standard-of-care lung ultrasound (POCUS), after which hospital outcomes will be registered. Primary outcome will be the sensitivity of this ultrasound marker for in-hospital deterioration (progression to NIV of death). Secondary analysis will include predictive models.

3.3 Research question What is the sensitivity of the diaphragm motion ratio (tidal/maximum) during ultrasound for in-hospital deterioration (progression to NIV or death) in AECOPD.

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

See summary

Study Type

Study Type

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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.
186

Contacts and Locations

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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

  • Netherlands
    • Overijssel
      • Zwolle, Overijssel, Netherlands, 8025AB
        • Recruiting
        • Isala
    • Provincie Groningen
      • Groningen, Provincie Groningen, Netherlands, 9713GZ

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

Probability Sample

Study Population

Hospitalized AECOPD patients

Description

• Inclusion criteria:

In order to be eligible to participate in this study, a subject must meet all of the following criteria:

  • Hospitalization primarily because of severe acute exacerbation of COPD
  • Spirometry record within last 5 years, with: post-bronchodilator FEV1/FVC < 0,70 and FEV1% < 80%predicted

  • Minimum of 10 packyears

    • Exclusion criteria:

A potential subject who meets any of the following criteria will be excluded from participation in this study:

  • Established diagnosis of diaphragm diaphragm paralysis.
  • Inability for diaphragm imaging (e.g. mechanical ventilation, or unable to follow vocal instructions).
  • Those not able or unwilling to give written informed consent.
  • Pregnant women

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.
study group
Study group will receive ultrasound of the diaphragm on admission for acute exacerbation COPD. No further study interventions.

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
primary outcome
Time Frame: From enrollment to the end of hospitalization
The primary endpoint is the sensitivity of the diaphragm motion ratio (ultrasound marker) for predicting in-hospital deterioration (defined as progression to non-invasive ventilation or in-hospital death). Sensitivity will be calculated as: True Positives/(True Positives+False Negatives)
From enrollment to the end of hospitalization

Collaborators and Investigators

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Sponsor

Sponsor

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Isala

Study record dates

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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.
October 14, 2025

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.
October 1, 2026

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.
December 1, 2026

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).
November 19, 2025

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.
November 26, 2025

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.
December 2, 2025

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.
December 2, 2025

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.
November 26, 2025

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.
November 1, 2025

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.
  • Diaphragm 003

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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