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

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.

Study Overview

• Status: Unknown
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Placebo; Drug: Roflumilast 500

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Àlvar Agustí; Phone Number: 971 011 772; Email: info@ciberes.org
• Study Contact Backup: Name: Paloma Vaquer; Phone Number: 971 011 772; Email: pvaquer@ciberes.org

Study Locations

• Spain
  • Balearic Island
    • Bunyola, Balearic Island, Spain, 07110
      • Spanish Research Center for Respiratory Diseases
      • Contact: Paloma Vaquer; Phone Number: 0034971011772; Email: pvaquer@ciberes.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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20 cigarettes pack-yr (if former smokers withdrawn 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo 500 mcg , 12 weeks of treatment
Active Comparator: Roflumilast; Roflumilast 500 mcg	Drug: Roflumilast 500; Roflumilast 500 mcg , 12 weeks of treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Endotelial function	12 weeks

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Spanish Research Center for Respiratory Diseases
• Investigators: Principal Investigator: Julio Ancochea, Hospital Universitario La Princesa; Principal Investigator: Carlos Álvarez, Hospital Universitario Doce de Octubre; Principal Investigator: Pilar De Lucas, Hospital General Universitario Gregorio Marañón; Principal Investigator: Myriam Calle, Hospital Clínico Universitario San Carlos; Principal Investigator: Salvador Díaz, Hospital Universitario Ramon Y Cajal; Principal Investigator: Francisco García, Hospital Universitario La Paz; Principal Investigator: Rosa Malo, Hospital Universitario Puerta de Hierro; Principal Investigator: Germán Peces-Barba, Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Anticipated): July 1, 2012
• Study Completion (Anticipated): August 1, 2012

Study Registration Dates

• First Submitted: May 9, 2012
• First Submitted That Met QC Criteria: May 9, 2012
• First Posted (Estimate): May 10, 2012

Study Record Updates

• Last Update Posted (Estimate): May 10, 2012
• Last Update Submitted That Met QC Criteria: May 9, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: Chronic bronchitis; Post-bronchodilator FEV1<70% reference; Presence of estavlished CVD,; CVD equivalent or diabetes mellitus
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: CIB-ROF-2011-01; 2011-005047-27 (EudraCT Number)