Effects of ROFLUMILAST on Markers of Subclinical Atherosclerosis In Stable COPD; the ELASTIC-trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Change From Baseline in Carotid Femoral-Pulse Wave Velocity at Month 6
研究概览
简要总结
Chronic obstructive pulmonary disease is associated with a low grade systemic inflammatory process. Systemic inflammation is hypothesized to maintain cardiovascular morbidity and mortality in COPD. Early changes of vascular integrity can be detected via markers of subclinical atherosclerosis.
Selective Inhibition of phosphodiesterase subtype 4 describes a promising therapeutic option in COPD with beneficial impact on lung function and exacerbation rate. Moreover, an anti-inflammatory effect of phosphodiesterase-4 inhibition was confirmed by recent data.
The aim of this study is to assess the effects of the phosphodiesterase-4 inhibitor Roflumilast on firstly surrogates of subclinical atherosclerosis and secondly markers of systemic inflammation in the peripheral circulation of patients with stable chronic obstructive pulmonary disease.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Over 40 years of age
- •Smoking history of at least 10 pack years
- •Chronic obstructive pulmonary disease at Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II - IV diagnosed according to standard criteria.
- •History of at least one COPD exacerbation requiring systemic corticosteroid treatment or hospitalisation in the previous year
排除标准
- •Insufficient compliance to study medication (≤70% of tablets used) during 4 weeks run-in period
- •History of acute exacerbation 4 weeks prior to run-in period
- •Diagnosis of alpha-1-antitrypsin deficiency
- •Diagnosis of asthma
- •Acute respiratory infections (e.g. pneumonia)
- •Severe acute infectious diseases (e.g. active hepatitis, HIV)
- •Lung cancer
- •Bronchiectasis
- •Interstitial lung disease
- •Any other relevant lung disease
- •Acute myocardial infarction
- •Systolic left ventricular dysfunction
- •Congestive heart failure New York Heart Association Functional Classification (NYHA) severity grade IV
- •Haemodynamically significant cardiac arrhythmias or heart valve deformations
- •Peripheral arterial occlusive disease
- •Acute or chronic renal/hepatic failure
- •Active malignancy
- •Autoimmune disease
- •Pregnant or breastfeeding women
- •Women no using or not willing to use adequate contraceptive measures for the duration of the trial
- •Hypersensitivity to study medication or placebo
- •Severe psychiatric or neurological disorders or history of depression associated with suicidal ideation or behaviour
- •Galactose intolerance, lactase insufficiency or glucose-galactose malabsorption
研究组 & 干预措施
Roflumilast
Active arm including patients who receive the study drug (500µg Roflumilast once daily)
干预措施: Roflumilast (Drug)
Placebo
Control arm including patients who receive the placebo tablet (once daily)
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Carotid Femoral-Pulse Wave Velocity at Month 6
时间窗: baseline, month 6
Carotid femoral-Pulse Wave Velocity (cf-PWV) will be measured non-invasively via applanation tonometry (AtCor Medical, Sydney, Australia). Wave propagation time will be calculated by the system software, using an ECG-gated reference frame. Aortic PWV is defined as the distance between two recording sites (i.e. common carotid- and femoral artery) divided by the wave propagation time.
次要结局
- Change From Baseline in Reactive Hyperemia Index at Month 6(baseline, month 6)
- Change From Baseline in 6-Minute Walk Test at Month 6(baseline, month 6)
- Change From Baseline in Augmentation Index at Month 6(baseline, month 6)
- Change From Baseline in Asymmetric Dimethylarginine at Month 6(baseline, month 6)
- Change From Baseline in Tumor Necrosis Factor-alpha at Month 6(baseline, month 6)
- Change From Baseline in Forced Expiratory Volume in 1 Second at Month 6(baseline, month 6)
- Change From Baseline in Matrix Metalloproteinase-9(baseline, month 6)
- Change From Baseline in COPD Assessment Test at Month 6(baseline, month 6)