The Effects of Nocturnal Non-invasive Ventilation in Stable COPD

NCT ID: NCT03053973

Last Updated: 2023-11-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 116 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-13
• Study Completion Date: 2025-11-01

Brief Summary

Rationale:

Application of long-term non-invasive ventilation (NIV) in chronic obstructive pulmonary disease (COPD) patients with chronic hypercapnic respiratory failure (CHRF) has recently been shown to improve outcomes. However, the mechanism behind these improvements are unknown. We hypothesize that NIV stabilizes FEV1 via beneficial effects on inflammation and repair pathways in patients with COPD. In the present study we aim to investigate, in COPD patients with CHRF,

1. change in FEV1 after 3 months nocturnal NIV in stable hypercapnic COPD patients as compared to standard care

2. the relationship between FEV1 change and modification of systemic and airway inflammation and remodelling, lung hyperinflation, and airway morphology.

3. predictors of a favourable response to chronic NIV in COPD patients with CHRF. Study design: multicentre randomised controlled study investigating the effects of NIV on airway morphology, airway inflammation and remodelling in hypercapnic COPD patients including a control group that will postpone the initiation of NIV for 3 months. In addition we will investigate how patient demographics, patient and disease characteristics and systemic and airway inflammation predict the response to chronic NIV in severe stable COPD. To do this, all patients will be followed for 6 months after NIV initiation.

Main study parameters/endpoints: The main endpoint is the change FEV1 after 3 months. Furthermore, as we recognise that FEV1 might not be the most important patient-related outcome, we will assess which parameters affect health-related quality of life after 3 and 6 months.

Detailed Description

Rationale: Application of long-term non-invasive ventilation (NIV) in chronic obstructive pulmonary disease (COPD) patients with chronic hypercapnic respiratory failure (CHRF) has recently been shown to improve outcomes when applied with sufficiently high inspiratory pressures and adequate backup breathing frequencies (high-intensity NIV). Interestingly, it has been demonstrated that nocturnal NIV improves not only clinical but also physiological parameters like arterial carbon dioxide pressure (PaCO¬2¬) and forced expiratory volume in 1 second (FEV1) in patients with stable COPD. However, the mechanism behind these improvements are unknown. Furthermore, it is unclear whether this improvement in lung function influences health-related quality of life (HRQoL), the utmost goal of chronic NIV in COPD, or that other baseline patient- and ventilatory characteristics are more important in predicting a long-term beneficial effect.

We hypothesize that NIV stabilizes FEV1 via beneficial effects on inflammation and repair pathways in the airways of patients with COPD. We aim to study this hypothesis and to investigate the regulation of lung function, markers of inflammation and repair pathways in airway biopsies, bronchial wash and bronchial and nasal epithelium in response to home mechanical ventilation. The second goal of this study is to define a phenotype of patients with COPD, based on baseline characteristics and biomarkers, such as markers of inflammation, who will respond to NIV therapy with improvements in lung function and HRQoL.

Objectives:

1. To investigate change in FEV1 after 3 months nocturnal NIV in stable hypercapnic COPd patients as compared to standard care

2. To investigate the relationship between FEV1 change and modification of systemic and airway inflammation and remodelling, lung hyperinflation, and airway morphology.

3. To investigate predictors of a favourable response to chronic NIV in COPD patients with CHRF.

Study design: The study is multicentre randomised controlled study investigating the effects of NIV on airway morphology, airway inflammation and remodelling in hypercapnic COPD patients including a control group that will postpone the initiation of NIV for 3 months. To measure these parameters a bronchoscopy with a bronchial wash and bronchial biopsies and high-resolution CT-scanning we be done at baseline and after 3 months. In a addition we will investigate how patient demographics, patient and disease characteristics and systemic and airway inflammation predict the response to chronic NIV in severe stable COPD. To do this, all COPD patients initiated on NIV in our centre will be followed for 6 months after NIV initiation as part of the present study.

Study population: Patients who have an indication for NIV (COPD Global Initiative of Obstructive Lung Disease (GOLD) III or IV and a PaCO2 > 6.0 kilopascal (kPa) in stable disease) in the Netherlands will be asked to participate.

For investigating airway inflammation, to ensure safety during the bronchoscopies, patients with severe gas exchange derangements (i.e. PaCO2 > 8.0 kPa and /or partial arterial oxygen pressure (PaO2)<6.5 kPa at rest during spontaneous breathing), and instable cardiac comorbidities will be excluded. These patients will be included to be followed for 6 months prospectively after NIV initiation, according to the same protocol, however, without CT-scanning and bronchoscopies.

Main study parameters/endpoints: The main endpoint is the change FEV1 after 3 months. Several markers of blood and airway inflammation and remodeling will be assessed to analyse mechanisms of FEV1 improvements.

Furthermore, as we recognise that FEV1 might not be the most important patient-related outcome, we will assess which parameters affect health-related quality of life after 3 and 6 months. For this, parameters of the total group of patients will be used.

Conditions

Noninvasive Ventilation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

NIV directly started arm

Patients randomised to this arm will start noninvasive ventilation after baseline measurements are performed.

Group Type: EXPERIMENTAL

nocturnal noninvasive ventilation

Intervention Type: DEVICE

Patients will be initiated on bilevel positive pressure non-invasive ventilation via a mask according to regular clinical practice.

Standard Care

Intervention Type: OTHER

Standard COPD care is given to all patients (pharmacological management, oxygen, rehabilitation if neccesary, etc.)

NIV postponed arm

Patients randomised to this arm will, after baseline measurements have been done, first be followed for 3 months while on standard care, and thus serve as the control arm. After this 3 months period, measurements are repeated and patients will also be initiated on noninvasive ventilation.

Group Type: OTHER

nocturnal noninvasive ventilation

Intervention Type: DEVICE

Patients will be initiated on bilevel positive pressure non-invasive ventilation via a mask according to regular clinical practice.

Standard Care

Intervention Type: OTHER

Standard COPD care is given to all patients (pharmacological management, oxygen, rehabilitation if neccesary, etc.)

Interventions

nocturnal noninvasive ventilation

Patients will be initiated on bilevel positive pressure non-invasive ventilation via a mask according to regular clinical practice.

Intervention Type: DEVICE

Standard Care

Standard COPD care is given to all patients (pharmacological management, oxygen, rehabilitation if neccesary, etc.)

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Indication to initiate chronic NIV in COPD patients (GOLD stage III or IV: FEV1/ forced expiratory volume (FVC)< 70% and FEV1< 50% predicted; PaCO2 > 6.0 kilopascal (kPa) in stable condition, which means no COPD exacerbation for 4 weeks and a pH > 7.35)
• Age > 18 years
• Written informed consent is obtained

Exclusion Criteria

For the randomised Inflammation part a potential subject who meets any of the following criteria will be excluded from participation in this study:

• Oral corticosteroids or roflumilast
• A history of lung volume reduction surgery
• Body mass index (BMI) > 35 kg/m2
• Obstructive sleep apnoea (OSA) (apnoea/hypopnea index (AHI) >15/hr): to exclude OSA a polygraphy will be done at baseline
• PaCO2 ≥ 8.0 kPa or PaO2 < 6.5 kPa at rest without oxygen
• Instable cardiac comorbidities (left ventricular ejection fraction (LVEF) <40%, instable coronary artery disease, instable heart failure)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peter Wijkstra

OTHER

Sponsor Role: lead

Responsible Party

Peter Wijkstra

Prof. Dr. P.J.Wijkstra

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Peter J Wijkstra, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

Locations

University Medical Center Groningen

Groningen, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Facility Contacts

Marieke Duiverman, MD PhD

Role: primary

m.l.duiverman@umcg.nl

0031-50-361616161

Peter Wijkstra, Prof

Role: backup

p.j.wijkstra@umcg.nl

References

Boersma R, Bakker JT, de Vries M, Raveling T, Slebos DJ, Wijkstra PJ, Hartman JE, Duiverman ML. Defining a phenotype of severe COPD patients who develop chronic hypercapnia. Respir Med. 2024 Nov-Dec;234:107850. doi: 10.1016/j.rmed.2024.107850. Epub 2024 Oct 31.

Reference Type: DERIVED

PMID: 39488255 (View on PubMed)

Other Identifiers

201700097

Identifier Type: -

Identifier Source: org_study_id