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

This study is ongoing, but not recruiting participants.
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: September 21, 2015
Last verified: September 2015

June 4, 2012
September 21, 2015
May 2012
January 2016   (final data collection date for primary outcome measure)
Change from baseline in carotid femoral-Pulse Wave Velocity at month 6 [ Time Frame: baseline, month 6 ] [ 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.
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.
Complete list of historical versions of study NCT01630200 on ClinicalTrials.gov Archive Site
  • Change from baseline in Reactive Hyperemia Index at month 6 [ Time Frame: baseline, month 6 ] [ 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.
  • Change from baseline in Augmentation Index at month 6 [ Time Frame: baseline, month 6 ] [ 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.
  • 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.
Not Provided
Not Provided
 
Effects of ROFLUMILAST on Subclinical Atherosclerosis in Chronic Obstructive Pulmonary Disease (COPD)
Effects of ROFLUMILAST on Markers of Subclinical Atherosclerosis In Stable COPD; the ELASTIC-trial

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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Chronic Obstructive Pulmonary Disease and Allied Conditions
  • Drug: Roflumilast
    Roflumilast coated tablet, 500µg oral application, once daily in the morning
    Other Name: Daxas
  • Drug: Placebo
    Placebo coated tablet (visually identical to 500µg Roflumilast tablet), oral application, once daily in the morning
    Other Name: n.a.
  • Active Comparator: Roflumilast
    Active arm including patients who receive the study drug (500µg Roflumilast once daily)
    Intervention: Drug: Roflumilast
  • Placebo Comparator: Placebo
    Control arm including patients who receive the placebo tablet (once daily)
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
80
January 2016
January 2016   (final data collection date for primary outcome measure)

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
Both
40 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
Austria
 
NCT01630200
ELASTIC2011
Yes
Not Provided
Not Provided
LudwLudwig Boltzmann Institute for COPD and Respiratory Epidemiology
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
LudwLudwig Boltzmann Institute for COPD and Respiratory Epidemiology
September 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP