Clinical trial NCT01630200: Effects of ROFLUMILAST on Subclinical Atherosclerosis in Chronic Obstructive Pulmonary Disease (COPD)
Official title: Effects of ROFLUMILAST on Markers of Subclinical Atherosclerosis In Stable COPD; the ELASTIC-trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Obstructive Pulmonary Disease and Allied Conditions
Keywords: COPD
comorbidity
arterial stiffness
roflumilast
Lead sponsor: LudwLudwig Boltzmann Institute for COPD and Respiratory Epidemiology
Sponsor class: NETWORK
Collaborators: name: Medical University of Vienna
First posted: 2012-06-28
Enrollment: 80
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change From Baseline in Carotid Femoral-Pulse Wave Velocity at Month 6
timeFrame: baseline, month 6
Secondary outcomes:
measure: Change From Baseline in Reactive Hyperemia Index at Month 6
timeFrame: baseline, month 6
measure: Change From Baseline in Augmentation Index at Month 6
timeFrame: baseline, month 6
measure: Change From Baseline in Matrix Metalloproteinase-9
timeFrame: baseline, month 6
measure: Change From Baseline in Asymmetric Dimethylarginine at Month 6
timeFrame: baseline, month 6
measure: Change From Baseline in Tumor Necrosis Factor-alpha at Month 6
timeFrame: baseline, month 6
measure: Change From Baseline in Forced Expiratory Volume in 1 Second at Month 6
timeFrame: baseline, month 6
measure: Change From Baseline in 6-Minute Walk Test at Month 6
timeFrame: baseline, month 6
measure: Change From Baseline in COPD Assessment Test at Month 6
timeFrame: baseline, month 6
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Deparment for Respiratory and Critical Care Medicine, Otto Wangner Hospital
Study officials:
affiliation: Department for Respiratory and Critical Care Medicine, Otto Wagner Hospital, Vienna
name: Otto C Burghuber, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Urban MH, Kreibich N, Gleiss A, Funk GC, Hartl S, Burghuber OC. Effects of roflumilast on arterial stiffness in COPD (ELASTIC): A randomized trial. Respirology. 2021 Feb;26(2):153-160. doi: 10.1111/resp.13914. Epub 2020 Jul 28.