Effects of ROFLUMILAST on Subclinical Atherosclerosis in Chronic Obstructive Pulmonary Disease (COPD)

NCT01630200 | Completed Phase 4 Results DMC

• 1 other identifier: ELASTIC2011
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Obstructive Pulmonary Disease and Allied Conditions

Keywords

COPD; comorbidity; arterial stiffness; roflumilast

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Carotid Femoral-Pulse Wave Velocity at Month 6

  Carotid femoral-Pulse Wave Velocity (cf-PWV) will be measured non-invasively via applanation tonometry (AtCor Medical, Sydney, Australia). Wave propagation time will be calculated by the system software, using an ECG-gated reference frame. Aortic PWV is defined as the distance between two recording sites (i.e. common carotid- and femoral artery) divided by the wave propagation time.

  baseline, month 6

Secondary Outcomes (8)

• Change From Baseline in Reactive Hyperemia Index at Month 6

  baseline, month 6

• Change From Baseline in Augmentation Index at Month 6

  baseline, month 6

• Change From Baseline in Matrix Metalloproteinase-9

  baseline, month 6

• Change From Baseline in Asymmetric Dimethylarginine at Month 6

  baseline, month 6

• Change From Baseline in Tumor Necrosis Factor-alpha at Month 6

  baseline, month 6

Study Arms (2)

Roflumilast

ACTIVE COMPARATOR

Active arm including patients who receive the study drug (500µg Roflumilast once daily)

Drug: Roflumilast

Placebo

PLACEBO COMPARATOR

Control arm including patients who receive the placebo tablet (once daily)

Drug: Placebo

Interventions

Roflumilast DRUG

Roflumilast coated tablet, 500µg oral application, once daily in the morning

Also known as: Daxas

Roflumilast

Placebo DRUG

Placebo coated tablet (visually identical to 500µg Roflumilast tablet), oral application, once daily in the morning

Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• LudwLudwig Boltzmann Institute for COPD and Respiratory Epidemiology: lead
• Medical University of Vienna: collaborator

Study Sites (1)

Deparment for Respiratory and Critical Care Medicine, Otto Wangner Hospital

Vienna, 1140, Austria

Location

Related Publications (1)

• Urban MH, Kreibich N, Gleiss A, Funk GC, Hartl S, Burghuber OC. Effects of roflumilast on arterial stiffness in COPD (ELASTIC): A randomized trial. Respirology. 2021 Feb;26(2):153-160. doi: 10.1111/resp.13914. Epub 2020 Jul 28.

  PMID: 32725799 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Roflumilast

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Matthias Urban
• Organization: Ludwig Boltzmann Institute for COPD and Respiratory Epidemiology

matthias.urban1@gmx.net

+43(0)6508125980

Study Officials

• Otto C Burghuber, M.D.

  Department for Respiratory and Critical Care Medicine, Otto Wagner Hospital, Vienna

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2012
• First Posted: June 28, 2012
• Study Start: May 1, 2012
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: April 12, 2019
• Results First Posted: April 12, 2019

Record last verified: 2019-01

Locations

AU (1)