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

This study is currently recruiting participants.
Verified June 2012 by LudwLudwig Boltzmann Institute for COPD and Respiratory Epidemiology
Sponsor:
Collaborator:
Medical University of Vienna
Information provided by (Responsible Party):
LudwLudwig Boltzmann Institute for COPD and Respiratory Epidemiology
ClinicalTrials.gov Identifier:
NCT01630200
First received: June 4, 2012
Last updated: June 27, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease and Allied Conditions
Drug: Roflumilast
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of ROFLUMILAST on Markers of Subclinical Atherosclerosis In Stable COPD; the ELASTIC-trial

Resource links provided by NLM:


Further study details as provided by LudwLudwig Boltzmann Institute for COPD and Respiratory Epidemiology:

Primary Outcome Measures:
  • carotid femoral-Pulse Wave Velocity [ Time Frame: 6 month ] [ Designated as safety issue: No ]
    Carotid femoral-Pulse Wave Velocity (cf-PWV) will be measured non-invasively with the well validated SphygmoCor system (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.


Secondary Outcome Measures:
  • Reactive Hyperemia Index [ Time Frame: 6 month ] [ Designated as safety issue: No ]
    Endothelial dysfunction will be assessed by means of the EndoPat device (Itamar Medical Ltd). This validated system measures the pulse wave amplitudes at the tip of both index fingers. The dominant arm will be occluded for 5 minutes by a sphygmomanometric cuff. After cuff deflation the pulse wave amplitude will be assessed to finally calculate the ratio of pulse wave amplitude before and after cuff-induced hyperemia. The so called reactive hyperemia index represents endothelial dysfunction at the level of conduit as well as resistance vessels.

  • Augmentation Index [ Time Frame: 6 month ] [ Designated as safety issue: No ]
    The curve of the peripheral pressure wave will be recorded from the radial artery. Augmentation index (Aix) will be calculated from the generated central aortic pressure waveform via pulse wave analysis function. To correct for respective influences, Aix will be adjusted for a heart rate of 75 bpm. Appropriate intra observer validity will be assured via an operator index ≥ 80.


Estimated Enrollment: 80
Study Start Date: May 2012
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Roflumilast
Active arm including patients who receive the study drug (500µg Roflumilast once daily)
Drug: Roflumilast
Roflumilast coated tablet, 500µg oral application, once daily in the morning
Other Name: Daxas
Placebo Comparator: Placebo
Control arm including patients who receive the placebo tablet (once daily)
Drug: Placebo
Placebo coated tablet (visually identical to 500µg Roflumilast tablet), oral application, once daily in the morning
Other Name: n.a.

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Over 40 years of age
  • Smoking history of at least 10 pack years
  • Chronic obstructive pulmonary disease at GOLD-stage II - IV diagnosed according to standard criteria (18)
  • History of at least one COPD exacerbation requiring systemic corticosteroid treatment or hospitalisation in the previous year

Exclusion Criteria:

  • 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 NYHA (New York Heart Association Functional Classification) severity grade IV)
  • Haemodynamically significant cardiac arrhythmias or heart valve deformations
  • Peripheral arterial occlusive disease
  • Acute or chronic renal/hepatic failure
  • Active malignancy
  • Autoimmune disease
  • Pregnant or breastfeeding women
  • Women no using or not willing to use adequate contraceptive measures for the duration of the trial
  • Hypersensitivity to study medication or placebo
  • Severe psychiatric or neurological disorders or history of depression associated with suicidal ideation or behaviour
  • Galactose intolerance, lactase insufficiency or glucose-galactose malabsorption
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01630200

Contacts
Contact: Matthias Urban, M.D. +43(0)1 91060 ext 41251 matthias.urban@wienkav.at
Contact: Nicole kreibich +43(0)1 91060 ext 41251 nicole.kreibich@extern.wienkav.at

Locations
Austria
Deparment for Respiratory and Critical Care Medicine, Otto Wangner Hospital Recruiting
Vienna, Austria, 1140
Contact: Matthias Urban, M.D.    +43 (0)1 91060 ext 41251    matthias.urban@wienkav.at   
Contact: Nicole Kreibich    +43 (0)1 91060 ext 41251    nicole.kreibich@extern.wienkav.at   
Principal Investigator: Otto C Burghuber, M.D.         
Sub-Investigator: Matthias Urban, M.D.         
Sponsors and Collaborators
LudwLudwig Boltzmann Institute for COPD and Respiratory Epidemiology
Medical University of Vienna
Investigators
Principal Investigator: Otto C Burghuber, M.D. Department for Respiratory and Critical Care Medicine, Otto Wagner Hospital, Vienna
  More Information

No publications provided

Responsible Party: LudwLudwig Boltzmann Institute for COPD and Respiratory Epidemiology
ClinicalTrials.gov Identifier: NCT01630200     History of Changes
Other Study ID Numbers: ELASTIC2011
Study First Received: June 4, 2012
Last Updated: June 27, 2012
Health Authority: Austria: Ethikkommission

Keywords provided by LudwLudwig Boltzmann Institute for COPD and Respiratory Epidemiology:
COPD
comorbidity
arterial stiffness
roflumilast

Additional relevant MeSH terms:
Atherosclerosis
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on April 16, 2014