Nocturnal Non-Invasive Ventilation in COPD Patients With Stable Hypercapnic Respiratory Failure: Why and in Which Patient Might This be Effective?
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 116
- 试验地点
- 2
- 主要终点
- FEV1
研究概览
简要总结
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.
详细描述
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 between FEV1 change and modification of systemic and airway inflammation and remodelling, lung hyperinflation, and airway morphology.
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
结局指标
主要结局
FEV1
时间窗: baseline, 3 months
Change in Forced expiratory volume in one second
Health-Related Quality of Life
时间窗: baseline, 3 months, 6 months
Change in HRQoL assessed by the severe respiratory insufficiency questionnaire summary score (SRI)
次要结局
- HRQoL assessed with CCQ(Baseline, 3 months, 6 months)
- Patient-ventilator asynchrony(baseline, 3 months)
- Respiratory muscle activity(baseline, 3 months)
- Exercise tolerance(baseline, 3 months, 6 months)
- Urine albumin to Creatinine ratio(Baseline, 3 months)
- Health-related quality of life assessed with the SF-36(baseline, 3 months, 6 months)
- Caregiver Burden(baseline, 3 months, 6 months)
- Nasal epithelium markers of remodelling and repair(Baseline, 3 months)
- Lung volumes(baseline, 3 months, 6 months)
- Emphysema(baseline, 3 months)
- Anxiety and depression(baseline, 3 months, 6 months)
- Activities and Restrictions,(baseline, 3 months, 6 months)
- Dyspnoea(baseline, 3 months, 6 months)
- Gas exchange night(baseline, 3 months, 6 months)
- Spirometry(baseline, 3 months, 6 months)
- Compliance with the ventilator(baseline, 3 months, 6 months)
- Venous blood(Baseline, 3 months)
- Airway inflammation and remodeling(Baseline, 3 months)
- Safety: the number of adverse events will be recorded.(baseline, 3 months, and 6 months)
- Gas exchange day(baseline, 3 months, 6 months)
- Peripheral muscle function(baseline, 3 months)
- Airway abnormalities(Baseline, 3 months)
研究者
Peter Wijkstra
Prof. Dr. P.J.Wijkstra
University Medical Center Groningen