Clinical trial NCT01595750: Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effect of Roflumilast on Endothelial Function in Patients With Chronic Obstructive Pulmonary Disease
Official title: Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effect of Roflumilast on Endothelial Function in Patients With Chronic Obstructive Pulmonary Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: Post-bronchodilator FEV1<70% reference
Chronic bronchitis
Presence of estavlished CVD,
CVD equivalent or diabetes mellitus
Lead sponsor: Spanish Research Center for Respiratory Diseases
Sponsor class: OTHER
First posted: 2012-05-10
Enrollment: 150
Sex: ALL
Minimum age (years): 55
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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20 cigarettes pack-yr (if former smokers withdrawn \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

Primary outcomes:
measure: Endotelial function
timeFrame: 12 weeks
Secondary outcomes:
measure: Arterial siffness
timeFrame: 12 weeks
measure: 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)
timeFrame: 12 weeks
measure: Serum oxidatrive stress markers: MPO, TRX
timeFrame: 12 weeks
measure: Serum endothelial dysfunction markers:TWEAKs, FasL, ADMA
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Bunyola
country: Spain
facility: Spanish Research Center for Respiratory Diseases
state: Balearic Island
Study officials:
affiliation: Hospital Universitario La Princesa
name: Julio Ancochea
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Doce de Octubre
name: Carlos Álvarez
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital General Universitario Gregorio Marañón
name: Pilar De Lucas
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clínico Universitario San Carlos
name: Myriam Calle
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Ramón y Cajal
name: Salvador Díaz
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario La Paz
name: Francisco García
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Puerta de Hierro
name: Rosa Malo
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz
name: Germán Peces-Barba
role: PRINCIPAL_INVESTIGATOR
References: