Clinical Trial: The Effects of Nocturnal Non-invasive Ventilation in Stable COPD
Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional
Official Title: Nocturnal Non-Invasive Ventilation in COPD Patients With Stable Hypercapnic Respiratory Failure: Why and in Which Patient Might This be Effective?
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,
- change in FEV1 after 3 months nocturnal NIV in stable hypercapnic COPD patients as compared to standard care
- the relationship between FEV1 change and modification of systemic and airway inflammation and remodelling, lung hyperinflation, and airway morphology.
- 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 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 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:
- To investigate change in FEV1 after 3 months nocturnal NIV in stable hypercapnic COPd patients as compared to standard care
- To investigate the relationship bet
Sponsor: Peter Wijkstra
Current Primary Outcome:
- FEV1 [ Time Frame: baseline, 3 months ]Change in Forced expiratory volume in one second
- Health-Related Quality of Life [ Time Frame: baseline, 3 months, 6 months ]Change in HRQoL assessed by the severe respiratory insufficiency questionnaire summary score (SRI)
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Safety: the number of adverse events will be recorded. [ Time Frame: baseline, 3 months, and 6 months ]The number of adverse events will be recorded.
- Health-related quality of life assessed with the SF-36 [ Time Frame: baseline, 3 months, 6 months ]Additional assessment of generic and disease specific aspects of HRQoL, evaluated with the SF-36.
- Anxiety and depression [ Time Frame: baseline, 3 months, 6 months ]Anxiety and depression, evaluated by the hospital anxiety and depression scale (HADS).
- Activities and Restrictions, [ Time Frame: baseline, 3 months, 6 months ]Activities and Restrictions, assessed with the Groningen Activity and Restriction Scale (GARS).
- Caregiver Burden [ Time Frame: baseline, 3 months, 6 months ]Caregiver Burden, assessed with the Caregiver Strain Index (CSI)
- Dyspnoea [ Time Frame: baseline, 3 months, 6 months ]Dyspnoea, using the Medical Research Council (MRC) score.
- Gas exchange day [ Time Frame: baseline, 3 months, 6 months ]Gas exchange at daytime without additional oxygen assessed with an arterial blood gas analysis
- Gas exchange night [ Time Frame: baseline, 3 months, 6 months ]Gas exchange during the night assessed with transcutaneous CO2 measurements.
- Respiratory muscle activity [ Time Frame: baseline, 3 months ]Respiratory muscle activity during the night and during NIV will be assessed with surface electromyography (EMG)
- Spirometry [ Time Frame: baseline, 3 months, 6 months ]Spirometry will be used to assess forced expiratory volumes
- Exercise tolerance [ Time Frame: baseline, 3 months, 6 months ]Exercise tolerance assessed by the 6-minute walking distance.
- Peripheral muscle function [ Time Frame: baseline, 3 months ]The 1-repetition maximum strength test will performed using a resistance weight-lifting machine
- Compliance with the ventilator [ Time Frame: baseline, 3 months, 6 months ]Compliance will be read from the ventilator counter readings
- Venous blood [ Time Frame: Baseline, 3 months ]Venous samples will be obtained for analyses of inflammatory markers
- Urine albumin to Creatinine ratio [ Time Frame: Baseline, 3 months ]Urine portion for albumin and creatinine will be obtained to obtain the albumin to creatinine ratio
- Nasal epithelium markers of remodelling and repair [ Time Frame: Baseline, 3 months ]For detailed description see the airway brush markers.
- Airway abnormalities [ Time Frame: Baseline, 3 months ]Airway abnormalities will be assessed with a High Resolution computertomography (HRCT) scanning with in- and expiration.
- Airway inflammation and remodeling [ Time Frame: Baseline, 3 months ]Airway inflammation and remodeling assessed with bronchial brushes and washes and airway biopsies obtained through bronchoscopy. Several markers leading to one profile will be assessed
- HRQoL assessed with CCQ [ Time Frame: Baseline, 3 months, 6 months ]Additional assessment of generic and disease specific aspects of HRQoL, evaluated with the Clinical COPD Questionnaire (CCQ).
- Patient-ventilator asynchrony [ Time Frame: baseline, 3 months ]Patient-ventilator asynchrony during the night and during NIV will be assessed by comparing surface electromyography (EMG) signals with ventilator pressure tracings
- Lung volumes [ Time Frame: baseline, 3 months, 6 months ]Bodyplethysmography will be used to assess lung volumes
- Emphysema [ Time Frame: baseline, 3 months ]The amount of emphysema and air-trapping assessed with a High Resolution computertomography (HRCT) scanning with in- and expiration, and captured into an emphysema score.
Original Secondary Outcome: Same as current
Information By: University Medical Center Groningen
Dates:
Date Received: February 8, 2017
Date Started: June 1, 2017
Date Completion: December 1, 2020
Last Updated: February 12, 2017
Last Verified: February 2017
- FEV1 [ Time Frame: baseline, 3 months ]
