How Nocturnal Hypoventilation Predicts Long-term Response to Non-invasive Ventilation in Hypercapnic COPD Patients (HYPONIV)

February 10, 2026 updated by: IRCCS Azienda Ospedaliero-Universitaria di Bologna

Role of Nocturnal Hypoventilation in Predicting the Long-Term Ventilatory Response in Hypercapnic COPD Patients Treated With Non-Invasive Ventilation: A Prospective Observational Study With Clinical, Functional, and Radiological Assessment

The study is an observational, single-center, prospective cohort study aiming to evaluate respiratory mechanics data, as well as clinical and functional parameters commonly used in clinical practice in patients with COPD and hypercapnic respiratory failure. The study population consists of patients with COPD and hypercapnia requiring NIV. The primary objective of the study is to evaluate the association between the reduction in partial pressure of carbon dioxide in arterial blood (PaCO₂) levels at 6 and 12 months after initiating non-invasive ventilation (NIV) and the presence of nocturnal hypoventilation detected at baseline in patients with COPD and chronic hypercapnia. Secondary objectives of this study are the evaluation of the following parameters measured at baseline and/or after 6 and 12 months of NIV treatment in patients with COPD and chronic hypercapnia:

  • Magnitude of esophageal pressure swing during nocturnal monitoring.
  • Diaphragm thickness and diaphragmatic thickening fraction assessed by thoracic ultrasound.
  • Presence of overlap syndrome (COPD + OSA).
  • Radiological classification of COPD subtypes to assess the association between radiological findings, functional profile, severity of nocturnal hypoventilation, and patterns of chronic hypercapnia.
  • Respiratory functional parameters, including FEV₁, FVC, FEV₁/FVC ratio, carbon monoxide diffusion capacity (DLCO), and airway resistance (R5 and R20).
  • Frequency of severe exacerbations and subsequent rehospitalizations during follow-up.
  • Rate of compliance with respiratory treatment.

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

To date, the pathophysiological mechanisms underlying the development of persistent hypercapnia in patients with COPD are not completely understood. Likewise, reliable predictive markers capable of identifying both patients at risk of developing this condition and those who may derive the greatest benefit from long-term non-invasive ventilation (NIV) are still lacking. Early identification of a patient phenotype more responsive to this type of intervention could substantially reduce exacerbations, emergency department visits, hospitalizations, and associated healthcare costs, thereby improving the overall efficiency of the local healthcare system. The aim of this study is therefore to identify more accurate and earlier criteria to recognize patients with COPD and hypercapnic respiratory failure who may benefit from long-term non-invasive ventilatory support, through an integrated analysis of respiratory mechanics data and clinical and functional parameters commonly used in routine clinical practice.

The study population consists of patients with COPD and hypercapnic respiratory failure who require NIV and who are evaluated in the outpatient clinic and/or inpatient unit of the Respiratory and Critical Care Unit of the IRCCS AOU of Bologna. For these patients clinical, functional, and respiratory mechanics data will be collected. Data will be collected at the baseline visit-corresponding to the first visit at the OSAS Ventilated outpatient clinic or the first day of hospitalization in the Pneumology and Respiratory Intensive Care Unit-and during follow-up visits, scheduled according to routine clinical practice at 6 and 12 months after initiation of NIV treatment.

The total duration of the study will be 30 months, including 12 months for patient enrollment, 12 months of follow-up, and 6 months for data analysis.

A total of 25 patients will be included.

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.
25

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

  • Italy
      • Bologna, Italy, 40138
        • Recruiting
        • IRCCS Azienda Ospedaliero-Universitaria di Bologna
        • Contact:

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

The study population consists of patients with COPD and hypercapnic respiratory failure who require NIV and who are evaluated in the outpatient clinic and/or inpatient unit of the Respiratory and Critical Care Unit of the IRCCS AOU of Bologna.

Description

Inclusion Criteria:

  • Age ≥ 18 years
  • Patients with COPD and hypercapnia, defined as PaCO₂ > 50 mmHg either chronically or 4 weeks after an acute exacerbation requiring invasive or non-invasive mechanical ventilation
  • Provision of informed consent

Exclusion Criteria:

  • Progressive neurodegenerative diseases
  • Diaphragmatic disorders
  • Severe hemodynamic instability (>1 vasoactive agent for at least 24 hours)
  • Acute coronary syndrome (unstable angina / myocardial infarction)
  • Severe arrhythmias
  • Presence of contraindications to NIV
  • Cognitive impairment interfering with treatment adherence
  • Active and unstable coronary artery disease
  • Malignancies undergoing active treatment
  • Patients already receiving home non-invasive mechanical ventilation

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

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
The association between the reduction in PaCO₂ levels and the presence of nocturnal hypoventilation
Time Frame: PaCO₂ (mmHg), measured by ABG - baseline, 3, 6, and 12 months TcCO₂ (mmHg), measured by transcutaneous monitoring - baseline

The primary outcome is measured through arterial blood gas analysis (ABG) to determine PaCO₂ levels, and through transcutaneous monitoring of oxygen saturation and carbon dioxide (SpO₂ and TcCO₂) to assess the presence of nocturnal hypoventilation.

Nocturnal hypoventilation is defined as an increase in PaCO₂ during sleep (TcCO₂ >10 mmHg above daytime PaCO₂ with TcCO₂ >50 mmHg for at least 10 minutes, or TcCO₂ >55 mmHg for ≥25% of total sleep time).
PaCO₂ (mmHg), measured by ABG - baseline, 3, 6, and 12 months TcCO₂ (mmHg), measured by transcutaneous monitoring - baseline

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
Magnitude of esophageal pressure swing during nocturnal monitoring
Time Frame: Baseline
Placement of a nasogastric respiratory mechanics catheter equipped with an esophageal balloon, and measurement of maximal inspiratory pressure swing (ΔPES).
Baseline
Diaphragm thickness and diaphragmatic thickening fraction
Time Frame: Baseline
Assessment of diaphragm thickness variation (TDi-exp, measured from pleural to peritoneal line at end-expiration; normal <1.5 mm suggesting diaphragmatic weakness). Unit of measure: mm
Baseline
Diaphragmatic thickening fraction
Time Frame: Baseline
Thickening fraction will be measured with the following formula: TFdi = (inspiratory thickness - expiratory thickness) / expiratory thickness × 100). This outcome will be measure via thoracic ultrasound using a linear probe positioned sagittally along the axillary line at the 8th-9th intercostal space.
Baseline
Presence of overlap syndrome (COPD + OSA)
Time Frame: Baseline
Overnight cardiorespiratory monitoring
Baseline
Radiological classification of COPD subtypes
Time Frame: Baseline
Data collection from High-resolution computed tomography (HRCT) for morphological evaluation and structural phenotyping (presence or absence of: emphysema, airway-wall thickening, bronchiectasis, air trapping).
Baseline
Respiratory functional parameters
Time Frame: Baseline, 6 and 12 months
FEV₁, FVC, FEV₁/FVC ratio measured by spirometry. Unity of measure: L
Baseline, 6 and 12 months
Respiratory functional parameters
Time Frame: Baseline, 6 and 12 months
DLCO
Baseline, 6 and 12 months
Respiratory functional parameters
Time Frame: Baseline, 6 and 12 months
Resistance at 5 Hz (R5) and Resistance at 20 Hz (R20)
Baseline, 6 and 12 months
Respiratory functional parameters
Time Frame: Baseline, 6 and 12 months
6 Minutes Walking Test (6MWT)
Baseline, 6 and 12 months
Frequency of severe exacerbations
Time Frame: baseline, 6 and 12 months
number of hospital admissions, ICU admissions, high-dependency unit admissions, and episodes of acute hypercapnic respiratory failure (AHRF) throughout the study period.
baseline, 6 and 12 months
Compliance with respiratory treatment
Time Frame: baseline, 6 and 12 months
number of nights where the respiratory support has been used for at least 4 hours/night divided by the total number of nights during treatment.
baseline, 6 and 12 months

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.
IRCCS Azienda Ospedaliero-Universitaria di Bologna

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

  • Murray I, Paterson E, Thain G, Currie GP. Outcomes following non-invasive ventilation for hypercapnic exacerbations of chronic obstructive pulmonary disease. Thorax. 2011 Sep;66(9):825-6. doi: 10.1136/thx.2010.152264. Epub 2010 Dec 9. PMID: 21148571.

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.
December 10, 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.
December 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.
June 1, 2028

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).
December 12, 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.
February 10, 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.
February 17, 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.
February 17, 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.
February 10, 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.
December 1, 2025

More Information

Terms related to this study

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.
  • HYPONIV
  • 2023.0267 (Other Grant/Funding Number: Fondazione Cassa di Risparmio Bologna)

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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