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

Study Overview
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Brief Summary
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REVASC is a randomized, double-blind, placebo-controlled study which will involve 150 patients with chronic bronchitis and COPD diagnosed cardiovascular disease. The recruitment period beginimg in the coming weeks, will last nine months. Patients included in the study will receive treatment for three months with roflumilast 500 mg (75 patients) or placebo (75 patients) in a randomized manner. The CIBERES, as promoter of this study is expected to release final results for the third quarter of 2013. Eight centers in Madrid will be involved in this clinical trial: Fundación Jiménez Díaz, Hospital La Princesa, Hospital Gregorio Maranon Hospital Clinico San Carlos, Hospital La Paz, Hospital Ramón y Cajal Hospital Doce de Octubre and Hospital Puerta del Hierro. Roflumilast is a potent phosphodiesterase-4 inhibitor (PDE4). Its clinical efficacy has been studied in an extensive clinical program involving over 12,000 patients with COPD. In these studies, roflumilast (in combination with long-acting bronchodilators) reduced the number of exacerbations and improved lung function, especially in those patients with associated chronic bronchitis.

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

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Roflumilast 500
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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20 cigarettes pack-yr (if former smokers withdrawn 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: Serum CRP ≥ 2 and < 10 mg/l or 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

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo 500 mcg , 12 weeks of treatment<br>|
| Active Comparator: Roflumilast<br>Roflumilast 500 mcg | Drug: Roflumilast 500<br>* Roflumilast 500 mcg , 12 weeks of treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endotelial function |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arterial siffness |  | 12 weeks | 
| Serum and plasma inflammation markers: (CRP, fibrinogen, leucocytes, interleukin (IL)-8, IL-6, IL-10, tumor necrosis factor alpha (TNFα), sICAM-1, MCP-1, PARC/CCL-18) |  | 12 weeks | 
| Serum oxidatrive stress markers: MPO, TRX |  | 12 weeks | 
| Serum endothelial dysfunction markers:TWEAKs, FasL, ADMA |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post-bronchodilator FEV1<70% reference, Chronic bronchitis, Presence of estavlished CVD,, CVD equivalent or diabetes mellitus