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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01630200
Recruitment Status : Unknown
Verified September 2015 by LudwLudwig Boltzmann Institute for COPD and Respiratory Epidemiology.
Recruitment status was:  Active, not recruiting
First Posted : June 28, 2012
Last Update Posted : September 22, 2015
Medical University of Vienna
Information provided by (Responsible Party):
LudwLudwig Boltzmann Institute for COPD and Respiratory Epidemiology

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.

Condition or disease Intervention/treatment Phase
Chronic Obstructive Pulmonary Disease and Allied Conditions Drug: Roflumilast Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of ROFLUMILAST on Markers of Subclinical Atherosclerosis In Stable COPD; the ELASTIC-trial
Study Start Date : May 2012
Estimated Primary Completion Date : January 2016
Estimated Study Completion Date : January 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Roflumilast

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. Change from baseline in carotid femoral-Pulse Wave Velocity at month 6 [ Time Frame: baseline, month 6 ]
    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 :
  1. Change from baseline in Reactive Hyperemia Index at month 6 [ Time Frame: baseline, month 6 ]
    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.

  2. Change from baseline in Augmentation Index at month 6 [ Time Frame: baseline, month 6 ]
    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.

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Ages Eligible for Study:   40 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 New York Heart Association Functional Classification (NYHA) 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01630200

Deparment for Respiratory and Critical Care Medicine, Otto Wangner Hospital
Vienna, Austria, 1140
Sponsors and Collaborators
LudwLudwig Boltzmann Institute for COPD and Respiratory Epidemiology
Medical University of Vienna
Principal Investigator: Otto C Burghuber, M.D. Department for Respiratory and Critical Care Medicine, Otto Wagner Hospital, Vienna

Responsible Party: LudwLudwig Boltzmann Institute for COPD and Respiratory Epidemiology Identifier: NCT01630200     History of Changes
Other Study ID Numbers: ELASTIC2011
First Posted: June 28, 2012    Key Record Dates
Last Update Posted: September 22, 2015
Last Verified: September 2015

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

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