Effects of ROFLUMILAST on Subclinical Atherosclerosis in Chronic Obstructive Pulmonary Disease (COPD)
Condition: Chronic Obstructive Pulmonary Disease and Allied Conditions
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Atherosclerosis
Intervention: Roflumilast; Placebo
Intervention description: Roflumilast coated tablet, 500µg oral application, once daily in the morning; Placebo coated tablet (visually identical to 500µg Roflumilast tablet), oral application, once daily in the morning
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 80.0
Sex: All
Minimum age: 40 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: COPD; comorbidity; arterial stiffness; roflumilast

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