Effects of ROFLUMILAST on Subclinical Atherosclerosis in Chronic Obstructive Pulmonary Disease (COPD) (ELASTIC)
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.
|Chronic Obstructive Pulmonary Disease and Allied Conditions||Drug: Roflumilast Drug: Placebo||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Effects of ROFLUMILAST on Markers of Subclinical Atherosclerosis In Stable COPD; the ELASTIC-trial|
- 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.
- 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.
- 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.
|Study Start Date:||May 2012|
|Estimated Study Completion Date:||January 2016|
|Estimated Primary Completion Date:||January 2016 (Final data collection date for primary outcome measure)|
Active Comparator: Roflumilast
Active arm including patients who receive the study drug (500µg Roflumilast once daily)
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)
Placebo coated tablet (visually identical to 500µg Roflumilast tablet), oral application, once daily in the morning
Other Name: n.a.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01630200
|Deparment for Respiratory and Critical Care Medicine, Otto Wangner Hospital|
|Vienna, Austria, 1140|
|Principal Investigator:||Otto C Burghuber, M.D.||Department for Respiratory and Critical Care Medicine, Otto Wagner Hospital, Vienna|