Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effect of Roflumilast on Endothelial Function in Patients With Chronic Obstructive Pulmonary Disease (REVASC)

Inclusion Criteria:

• Signed informed consent
• 55-75 years of age
• Current and former smokers >20 cigarettes pack-yr (if former smokers withdrawn >1 year)
• Diagnosis COPD (GOLD criteria1 for more than a year before V0)
• Presence of chronic bronchitis (cough and/or expectoration for more that 3 months/yr for more than 2 consecutive yrs. in the absence of other potential cause)
• Post-bronchodilator FEV1<70% reference
• Presence of established CVD, CVD equivalent or diabetes mellitus

• Presence of chronic systemic inflammation, determined on:

  1. Serum CRP ≥ 2 and < 10 mg/l or
  2. Serum fibrinogen > 518 mg/dl and Leucocytes > 8,6*106 /mm3

Exclusion Criteria:

• Episode of COPD exacerbation and/or COPD treatment change during the last 2 months before V0
• History of asthma, significant residual lung lesions or bronchiectasis on chest x-ray
• Apnea-hypopnea syndrome
• Poorly controlled CVD risk factors (Table 2) and/or change in their treatment during the last 3 months before V0
• Clinically significant cardiac arrhythmias or valve disease
• Severe concomitant immunological, inflammatory, infectious or neoplastic diseases
• Moderate or severe hepatic insufficiency (B or C class, following Child-Pugh scale)
• Severe neurologic and/or psychiatric disorder, including depression with suicidal ideas
• Alcohol and/or drug abuse during the last 12 months before V0
• Hypersensitivity to roflumilast or to any of its excipients
• Pregnancy or potential pregnancy
• Participation in other clinical trial during the last 30 days before V0
• Language difficulties to follow the instructions of the study